The Center for Multiple Sclerosis and Autoimmune Neurology (CMSAN) Research Procedures (CMSAN)
Center for Multiple Sclerosis and Autoimmune Neurology Research Procedures
- 18 years or older.
- Both sexes will be enrolled.
- Neurological conditions that are suspected to be antibody mediated.
- All subjects will be required to have the capacity to give appropriate informed consent.
- Vulnerable study population.
- Infection on the skin at the site where the biopsy is to be performed.
- Bleeding disorders or people with a low number of platelets.
- Any allergy to medications used for numbing the areas during the procedures.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 1/30/23. Questions regarding updates should be directed to the study team contact.
Restoring elbow flexion in adult traumatic brachial plexus injuries with spinal accessory nerve versus intercostal nerve transfer
Spinal Accessory Nerve Versus Intercostal Nerve Transfer to Restore Elbow Flexion in Adult Traumatic Brachial Plexus Injuries
- Adult (≥ 18 years of age) traumatic brachial plexus injury (BPI) patients who underwent spinal accessory nerve or intercostal nerves transfer to musculocutaneous nerve or branch to biceps from Jan 1 2010 to Dec 31 2020.
- Once consented, they will be given an appointment to return to the Mayo Clinic Brachial Plexus clinic for a physical follow-up to undergo a standard post nerve reconstruction evaluation. For patients who consented but are not able to travel to Mayo Clinic for a physical review, a virtual consult will be scheduled.
- Patients less than 18 years old and those with brachial plexus palsy resulting from birth injury, compressive neuropathy, resection of tumors, cervical spine surgery, radiation therapy, inflammatory or auto-immune conditions will be excluded.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 1/11/23. Questions regarding updates should be directed to the study team contact.
A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH OUTCOMES)
A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)
- Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.
- Most recent biopsy (within last 5 years) shows cirrhosis with a NAS of ≥ 2, and at least two components: one being steatosis and at least one other component; OR NAS of ≥ 2, if steatosis = 0 or is ungraded with inflammation and/or ballooning, eligible with an MRI-PDFF > 5%. If steatosis and ballooning and/or steatosis and inflammation are noted by the local pathologist, then the biopsy qualifies even if a NAS is not provided (approximately 70% of the study patient population);
- Historical biopsy (within last 5 years) showed NASH with significant fibrosis with pathology report documenting "F2" or "F3", with at least steatosis either by biopsy with no minimal percentage required or by MRI-PDFF > 5%, AND inflammation or ballooning. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (up to approximately 20% of study patient population);
- Historical biopsy (within last 5 years) shows steatosis. Pathology report documents steatosis with no minimal percentage required. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy;
- Prescreening metabolic risk factors must include obesity and/or T2D. (Up to approximately 10% of study patient population).
- Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).
- At least 3 metabolic risk factors.
- MRI-PDFF
- Obtained during the Screening period; or
- If a subject is a re-screen, MRI-PDFF will be valid for up to 12 weeks at the time of randomization with no weight change ≥ 5% weight change in that interval.
- NOTE: In addition to evaluation of liver fat content, the MRI-PDFF will be evaluated by the MRI Core laboratory for spleen size and liver contour; any notable findings will be reported by the Core laboratory.
- NOTE: Patients with contraindications to an MRI-PDFF (e.g., metal prosthetics or uncontrolled documented claustrophobia, body weight exceeds limit of machine) examination are eligible for this study if the patient undergoes a FibroScan.
- MRE ≥ 4.2 where MRE is available.
- Enhanced liver function (ELF) ≥ 9.8, only if MRE is unavailable or contraindicated.
- Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson's disease, history or evidence of alpha-1-antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer, are excluded.
- MELD score ≥ 12 due to liver disease at either screening OR baseline (See Notes and Section 5).
- NOTE: MELD of ≥12 as the result of liver disease is exclusionary, NOT including isolated laboratory abnormalities such as elevated creatinine due to chronic kidney disease, INR abnormality secondary to anticoagulants or laboratory error, or bilirubin elevation due to Gilbert’s syndrome. UGT1A1 allele testing to be performed at Screening on all patients (where permitted).
- NOTE: A screening MELD of ≥ 12 that is likely due to liver disease may only be retested during screening in consultation with the Sponsor because of the possibility that the patient is not well-compensated. If the retest screening MELD is < 12 and all other conditions are met, the patient may randomize. If the baseline MELD is ≥ 12 in a patient who had a screening MELD ≥ 12 (even if the screening retest was < 12), the patient must permanently discontinue study drug and exit the Main MGL-3196-19 study.
- In a patient with a screening MELD < 12, if the baseline MELD is ≥ 12 and likely due to liver disease, the patient must discontinue study drug, and retest MELD within one week of randomization. If repeat MELD is < 12, the patient may restart study drug and continue in the study. If the retest shows MELD ≥ 12 then the patient must permanently discontinue study drug, but patient may continue in the study off study drug.
- History of hepatic decompensation or impairment at either screening or baseline, defined as presence of any of the following:
- History of variceal bleeding;
- NOTE: small to medium (Grade I-II) non-bleeding varices are allowed).
- Ascites due to cirrhosis. Screening MRI or CT shows at least a 2 cm pocket of fluid in at least 2 of 5 abdominal stations, including the four abdominal quadrants and pelvis;
- NOTE: in situations where both MRI and CT are contraindicated, ultrasound is acceptable for evaluation of ascites.
- Overt hepatic encephalopathy, lactulose treatment, or other treatment for hepatic encephalopathy Serum albumin 1.4 unless due to therapeutic anticoagulants or laboratory error;
- NOTE: If laboratory error is suspected, retest to confirm INR ≤ 1.4 is required).
- Total bilirubin ≥ 2 mg/dL;
- NOTE: Patients with genetically confirmed Gilbert’s syndrome are eligible with a total bilirubin ≥ 2 mg/dL if reticulocyte count is within normal limits, hemoglobin is within normal limits unless due to chronic anemia and unrelated to hemolysis, and direct bilirubin is < 20% of total bilirubin.
- Screening ECG shows uncontrolled cardiac arrythmia, or not previously diagnosed.
- NOTE: Patient may continue screening or rescreen if arrythmia is controlled (i.e., new onset asymptomatic atrial fibrillation that is appropriately followed up with appropriate treatment such as cardioversion and/or use of anticoagulants).
- Use of statin therapy exceeding the following doses is not allowed:
- Atorvastatin > 20 mg daily;
- Rosuvastatin > 20 mg daily;
- Simvastatin > 20 mg daily;
- Pravastatin > 40 mg daily;
- Lovastatin > 20 mg daily;
- Pitavastatin > 2 mg daily.
- NOTE: Dose adjustments in statins, consistent with label recommendations for hepatic impairment, cirrhosis or tolerability issues, may be made during the Screening period and during the study.
- NOTE. Other dyslipidemia therapies not specifically listed as prohibited in Appendix 5, such as PCSK9 inhibitors, fish oils and derivatives, are allowed. Fenofibrate is not allowed in this study.
- NOTE: In the case that a lipid lowering medication is discontinued or reduced before randomization, the patient can randomize one week after the discontinuation. An increase in lipid medication dose or a switch in statin (or other lipid lowering medication) as permitted in the protocol must be stable for at least two weeks prior to randomization.
- Prior treatment with NASH therapeutics in an investigational trial unless the following criteria are met:
- Follow up liver biopsy at the end of trial continued to show NASH cirrhosis meeting eligibility criteria for this trial and if they have been off the NASH therapeutic for at least 12 weeks prior to expected randomization; OR
- Potential NASH therapeutic studied revealed no safety issues, and, in fact, was not an effective NASH therapeutic (no effect on liver biopsy compared to placebo). Participation may occur 12 weeks or 5 half-lives, whichever is longer, after discontinuation of the therapy; OR
- Subjects who discontinued from an ongoing NASH cirrhosis study may be eligible after consultation with Medical Monitor and if they had participated in the study for less than 3 months and if they have been off the NASH therapeutic for at least 6 months prior to expected randomization.
- NOTE: Any patient who previously took resmetirom is excluded. If patient participated in a resmetirom clinical trial but was confirmed as randomized to placebo (never received resmetirom), they may be eligible to participate after discussion with the Sponsor as long as other eligibility criteria are met.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 12/26/23. Questions regarding updates should be directed to the study team contact.
A Phase III Randomized Trial for Newly Diagnosed Multiple Myeloma (NDMM) Patients Considered Frail or in a Subset of Intermediate Fit Comparing Upfront Three-Drug Induction Regimens Followed by Double or Single-Agent Maintenance
Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment
- Participants must have documented multiple myeloma satisfying standard International
Myeloma Working Group (IMWG) diagnostic criteria within 28 days prior to registration
- Participants must have measurable disease within 28 days prior to registration as
defined by any of the following:
- Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=
0.5 gram/deciliter [g/dL] or urine M-protein level >= 200 milligram[mg]/24
hours[hrs]); OR
- IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >= 0.2 g/dL or
urine M-protein level >= 200 mg/24 hrs); OR
- Light chain multiple myeloma (serum immunoglobulin free light chain >= 10 mg/dL
and abnormal serum immunoglobulin kappa lambda free light chain ratio)
- All disease must be assessed and documented on the baseline/pre-registration tumor
assessment form
- Participants must have a calculated myeloma frailty index (Myeloma Frailty Score
Calculator; http://www.myelomafrailtyscorecalculator.net/) categorized as frail or
intermediate fit (regardless of age) within 28 days prior to registration
- For Participants Meeting "Frail" Status:
- Participants with any degree of kidney dysfunction are allowed; however,
participants on dialysis are not eligible
- For Participants Meeting "Frail" Status:
- Hemoglobin >= 7 g/dL (must be performed within 28 days prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias
are considered secondary to bone marrow involvement from MM)
- For Participants Meeting "Frail" Status:
- Platelets >= 50 x 10^9/L (must be performed within 28 days prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias
are considered secondary to bone marrow involvement from MM)
- For Participants Meeting "Frail" Status:
- Absolute neutrophil count (ANC) >= 0.75 x10^9/L (must be performed within 28 days
prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias
are considered secondary to bone marrow involvement from MM)
- For Participants Meeting "Intermediate Fit" Status, one or more of the following
criteria must be present:
- Kidney dysfunction showing calculated creatinine clearance (CrCl) <30 ml/min.
- Actual lab serum creatinine value with a minimum of 0.7 mg/dL.
- Participants must have bone marrow function assessed and meet the below criteria
ranges:
- Hemoglobin between 7-8 g/dL, OR
- Platelets between 50-75 x10^9/L, OR
- ANC between 0.75-1 x10^9/L
- Note: growth factor and transfusion utilization are allowed as long as
cytopenias are considered secondary to bone marrow involvement from MM)
- Revised International Staging System (R-ISS) stage III disease
- Note: All labs must be performed within 28 days prior to registration
- Participants must have a complete medical history and physical exam within 28 days
prior to registration
- Participants must have whole body imaging within 60 days prior to registration. The
recommended method of imaging is a positron emission tomography/computed tomography
(PET/CT); a low-dose whole body CT scan or whole-body magnetic resonance imaging (MRI)
or skeletal survey should be done only if a PET/CT scan cannot be done or is
non-feasible. This must be documented in the comments section of the Onstudy form.
- Total bilirubin =< 2 times institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 × institutional
ULN (within 28 days prior to registration)
- Participants must have adequate cardiac function, as assessed by the treating
physician within 14 days prior to registration. Participants with known history or
current symptoms of cardiac disease, or history of treatment with cardiotoxic agents,
must have a clinical risk assessment of cardiac function using the New York Heart
Association Functional Classification and must not be assessed as class 3 or 4
- Participants with known diabetes must show evidence of controlled disease within 14
days prior to registration. Uncontrolled diabetes is defined as: A glycosylated
hemoglobin (Hg)A1C > 7
- Participants with known human immunodeficiency virus (HIV)-infection must be receiving
anti-retroviral therapy and have an undetectable viral load test on the most recent
test result obtained, within 6 months prior to registration
- All participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on treatment,
participant must have an undetectable HCV viral load within 28 days prior to
registration
- Participants must have an Eastern Cooperative Oncology Group (ECOG)/Zubrod performance
status score of 0-2 (Note: Participants with ECOG/Zubrod performance score [PS] 3,
especially where the deterioration of PS is considered secondary to the MM diagnosis,
will be allowed)
- Participants must be offered the opportunity to participate in specimen banking. With
participant consent, specimens must be collected and submitted via the Southwest
Oncology Group (SWOG) specimen tracking system
- Participants who are able to complete the patient-reported outcomes measures in
English or Spanish must agree to participate in the PRO portion of the study
- Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal
guidelines. For participants with impaired decision-making capabilities, legally
authorized representatives may sign and give informed consent on behalf of study
participants in accordance with applicable federal, local, and Central Institutional
Review Board (CIRB) regulations
- Participants must not have received any prior systemic therapy for multiple myeloma
with the exception of any one or more of the following:
- An emergency use of a short course of corticosteroids (equivalent of
dexamethasone 160 mg) any time before registration, or
- Up to one complete cycle of a non-daratumumab and hyaluronidase-fihj containing
anti-myeloma regimen (1 cycle = 21 or 28 days depending on the regimen being
used), or
- Localized palliative radiation therapy for multiple myeloma, as long as the
radiation therapy is completed at least 3 days prior to starting the systemic
treatment as per the study protocol.
- Participants must not have evidence of grade 4 peripheral neuropathy prior to study
registration
- Participants must not have uncontrolled blood pressure within 14 days prior to
registration. Uncontrolled blood pressure: systolic blood pressure (SBP) > 140 mmHg or
diastolic blood pressure (DBP) > 90 mmHg. Participants are permitted to be receiving
multiple anti-hypertensive medications (unless otherwise indicated in the study). All
blood pressure measurements within the 14 days prior to registration must be SBP =<
140 and DBP =< 90. A participant with a single blood pressure elevation who upon
rechecking has a normal blood pressure will remain eligible at the discretion of the
registering investigator.
- Participants must not have a prior or concurrent malignancy whose natural history or
treatment (in the opinion of the treating physician) has the potential to interfere
with the safety or efficacy assessment of the investigational regimen.
- Participants must not be pregnant or nursing. Individuals who are of reproductive
potential must have agreed to use an effective contraceptive method with details
provided as a part of the consent process. A person who has had menses at any time in
the preceding 24 consecutive months or who has semen likely to contain sperm is
considered to be of "reproductive potential." In addition to routine contraceptive
methods, "effective contraception" also includes refraining from sexual activity that
might result in pregnancy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,
bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the
semen.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/24/23. Questions regarding updates should be directed to the study team contact.
A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis
A Study to Determine the Efficacy and Safety of ABC008 for Inclusion Body Myositis
- Adult males and females age > 40 years at the time of the first dose of study medication;
- Weight > 40 and < 150 kg;
- Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the European Neuromuscular Centre (ENMC) IBM 2011 research diagnostic criteria (Rose et al., 2013). Documented histopathology results must be available prior to Baseline (Day 1) to confirm eligibility;
- Able to arise from a chair (with armrests), with use of their arms but without support from another person or device (e.g., cane, walking stick), at Screening and Baseline
(Day 1);
- Able to walk 3 meters, turn around, walk back to the chair, and sit down, with or without assistive device. Once arisen from the chair, subject may use any walking device but cannot be supported by another person, furniture, or a wall;
- Any other form of myositis or myopathy other than IBM; e.g., metabolic or drug-induced myopathy, drug-induced myositis, anti-synthetase syndrome, polymyositis or
dermatomyositis, cancer-associated myositis (myositis diagnosed within 3 years, either before or after), myositis in overlap with another autoimmune disease (e.g., systemic
lupus, systemic sclerosis, rheumatoid arthritis), or muscular dystrophy;
- Any condition; e.g., severe degenerative arthritis with limited range of motion, which precludes the ability to quantitate muscle strength or perform functional assessments (e.g., mTUG), in the Investigator's opinion;
- Presence of another autoimmune or autoinflammatory disease other than indication under study, e.g., rheumatoid arthritis, psoriatic arthritis, axial spondyloarthropathy,
inflammatory bowel disease, systemic lupus erythematosus. Subjects with Sjogren's syndrome, T-cell large granular lymphocyte leukemia (T-LGLL), or well-controlled
thyroid disease are permitted.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/15/23. Questions regarding updates should be directed to the study team contact.
Development and Validation of Novel Grading Scales to Assess Facial Nerve Function
Novel Grading Scales to Assess Facial Nerve Function: Development and Validation
- Adult patients (≥ 18 years of age) representing a range of early postoperative facial nerve function after surgery of the cerebellopontine angle, temporal bone, or parotid.
- Patients with preoperative (preexisting) facial nerve paralysis; patients with prior history of facial reanimation surgery; children (< 18 years of age).
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/22/23. Questions regarding updates should be directed to the study team contact.
Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve in Failing Aortic Bioprosthetic Valves
ALLIANCE AVIV: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve in Failing Aortic Bioprosthetic Valves
1. Failing aortic bioprosthetic valve demonstrating ≥ moderate stenosis and/or ≥ moderate
insufficiency
2. Bioprosthetic valve size suitable for SAPIEN X4 THV
3. NYHA functional class ≥ II
4. Heart Team agrees the subject is at high or greater surgical risk
5. The subject has been informed of the nature of the study, agrees to its provisions and
has provided written informed consent.
1. Anatomical characteristics that would preclude safe femoral placement of the
introducer sheath or safe passage of the delivery system
2. Failing valve has moderate or severe paravalvular regurgitation
3. Failing valve is unstable, rocking, or not structurally intact
4. Known severe patient-prosthesis mismatch or bioprosthetic valve with residual mean
gradient > 20 mmHg at the end of the index procedure for implantation of the original
valve
5. Increased risk of THV embolization
6. Surgical or transcatheter valve in the mitral position
7. Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis
8. Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months
9. Left ventricular ejection fraction < 20%
10. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
11. Increased risk of coronary artery obstruction after THV implantation
12. Myocardial infarction within 30 days prior to the study procedure
13. Hypertrophic cardiomyopathy with subvalvular obstruction
14. Subjects with planned concomitant ablation for atrial fibrillation
15. Clinically significant coronary artery disease requiring revascularization
16. Any surgical or transcatheter procedure within 30 days prior to the study procedure.
Implantation of a permanent pacemaker or implantable cardioverter defibrillator is not
considered an exclusion.
17. Any planned surgical or transcatheter intervention to be performed within 30 days
following the study procedure
18. Endocarditis within 180 days prior to the study procedure
19. Stroke, transient ischemic attack or neurological signs and symptoms attributed to
carotid or vertebrobasilar disease within 90 days prior to the study procedure
20. Hemodynamic or respiratory instability requiring inotropic or mechanical support
within 30 days prior to the study procedure
21. Renal insufficiency and/or renal replacement therapy
22. Leukopenia, anemia, thrombocytopenia
23. Inability to tolerate or condition precluding treatment with antithrombotic therapy
24. Hypercoagulable state or other condition that increases risk of thrombosis
25. Absolute contraindications or allergy to iodinated contrast that cannot be adequately
treated with premedication
26. Subject refuses blood products
27. Body mass index > 50 kg/m^2
28. Estimated life expectancy < 24 months
29. Female who is pregnant or lactating
30. Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that
could confound endpoint assessments
31. Participating in another investigational drug or device study that has not reached its
primary endpoint
32. Subject considered to be part of a vulnerable population
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/13/23. Questions regarding updates should be directed to the study team contact.
A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR) (AVANZAR)
Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin for First-Line Treatment of Patients With Advanced NSCLC Without Actionable Genomic Alterations
- Participants ≥ 18 years at screening
- Participants with histologically or cytologically documented NSCLC that is Stage IIIB
or IIIC disease not amenable for surgical resection or definitive chemoradiation or
Stage IV metastatic NSCLC disease at the time of randomisation, who have not received
prior chemotherapy or other systemic therapy for first-line Stage IIIB, IIIC or IV
- Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has
no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable
driver oncogenes with approved therapies (actionable genomic alterations).
- ECOG PS of 0 or 1
- Archival tumour tissue collected prior to signing of ICF
- Has adequate bone marrow reserve and organ function within 7 days before randomisation
- History of another primary malignancy except for malignancy treated with curative
intent with no known active disease within 3 years before the first dose of study
intervention and of low potential risk for recurrence
- Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
- Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade
≤ 1 or baseline (with exceptions)
- Active or prior documented autoimmune, connective tissue or inflammatory disorders
(with exceptions)
- Spinal cord compression or brain metastases unless asymptomatic, stable, not requiring
steroids for at least 7 days prior to randomisation, and a minimum of 2 weeks have
elapsed between the end of radiotherapy and study enrollment
- History of leptomeningeal carcinomatosis
- Clinically significant corneal disease
- Known active or uncontrolled hepatitis B or C virus infection
- Known HIV infection that is not well controlled
- History of non-infectious ILD/pneumonitis that required steroids, has current
ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging
at screening
Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination with Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants with Previously Treated Advanced Melanoma (TEBE-AM)
Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)
- HLA-A*02:01-positive.
- unresectable Stage III or Stage IV non-ocular melanoma
- archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not
previously irradiated has been provided.
- measurable or non-measurable disease per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- If applicable, must agree to use highly effective contraception
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the Informed Consent (ICF) and protocol
- Pregnant or lactating women
- diagnosis of ocular or metastatic uveal melanoma
- history of a malignant disease other than those being treated in this study
- ineligible to be retreated with pembrolizumab due to a treatment-related AE
- known untreated or symptomatic central nervous system (CNS) metastases and/or
carcinomatous meningitis
- previous severe hypersensitivity reaction to treatment with another monoclonal
antibody (mAb)
- active autoimmune disease requiring immunosuppressive treatment
- clinically significant medical condition
- known psychiatric or substance abuse disorders
- received prior treatment with a licensed or investigative Immune-mobilizing monoclonal
T-cell receptor Against Cancer (ImmTAC) medication
- received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb,
ipilimumab, and BRAF TKI regimen) within 14 days of first dose
- received cellular therapies within 90 days of first dose
- received systemic treatment with steroids or any other immunosuppressive drug within 2
weeks of first dose
- have not progressed on treatment with an anti-PD(L)1 mAb
- have not received prior ipilimumab
- a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen
- currently participating or have participated in a study of an investigational agent or
using an investigational device within 30 days of the first dose
- known history of chronic viral infections
- Out of range Laboratory values
- history of allogenic tissue/solid organ transplant
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 5/25/23. Questions regarding updates should be directed to the study team contact.
Sleep Related Breathing Disorders in Liver Transplant Candidates
Liver Transplant Candidates Sleep Related Breathing Disorders
- Age ≥ 18 years.
- Undergoing evaluation for potential liver.
- Fluency in any of the following languages English or Spanish.
- Age < 18.
- Color-blind (invalidates Stroop testing).
- Personal history of sleep apnea.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/7/23. Questions regarding updates should be directed to the study team contact.
Aqueous Humor Dynamics of NCX 470 Ophthalmic Solution – A Double Masked, Placebo Controlled, Phase 3b Clinical Trial (Whistler) (Whistler)
Aqueous Humor Dynamics of NCX 470 Ophthalmic Solution
1. ≥ 18 years of age
2. Either gender
3. Subjects without glaucoma
4. Qualifying IOP at Screening Visit
1. Narrow anterior chamber angles or disqualifying central corneal thickness in either eye
2. Clinically significant ocular disease in either eye
3. Uncontrolled systemic disease
4. Serious hypersensitivity to topical anesthetic eye drops
5. Subjects with a known hypersensitivity or contraindications to any of the ingredients in the study medications
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/5/23. Questions regarding updates should be directed to the study team contact.
Ventricular Remodeling and Myocardial Deformation in Patients Undergoing Chemotherapy for Sarcomas
Ventricular Remodeling and Myocardial Deformation in Patients Undergoing Chemotherapy for Sarcomas
- Patients followed at Mayo Clinic and treated for sarcoma with doxorubicin and/or pazopanib
- First-line treatment not including doxorubicin
- Treatment performed outside of Mayo Clinic with different protocols
- Age <18 years
Image-based Mapping of Brain Tumors
Image-based Mapping of Brain Tumors
Inclusion Criteria
- Prospective collection
- Undergoing diagnostic biopsy and/or surgical resection for brain tumor
- Retrospective collection
- Underwent treatment and/or diagnosis for suspected brain tumor
Exclusion Criteria
- Prospective collection only
- Unable to have an MRI
A Multi-Center, Prospective, Single-Arm, Observational Study to Evaluate Real-World Outcomes for the Shape-Sensing Ion Endoluminal System
Evaluating Real-World Outcomes for the Shape-Sensing Ion Endoluminal System
- Subject is 18 years or older at the time of the index procedure.
- Subject is a candidate for an elective, planned lung lesion localization or biopsy procedure utilizing the Ion Endoluminal System.
- Subject able to understand and adhere to study requirements and provide informed consent.
- Subject is under the care of a Legally Authorized Representative (LAR) and is unable to provide informed consent on their own accord.
- Subject is participating in an interventional research study or research study investigational agents with an unknown safety profile that would interfere with participation in this study.
- Female subjects who are pregnant or nursing at the time of the index bronchoscopy procedure, as determined by standard site practices.
- Subjects that are incarcerated or institutionalized under court order, or other vulnerable populations.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/24/23. Questions regarding updates should be directed to the study team contact.
Mount Sinai Acute Graft-versus-Host Disease International Consortium (MAGIC): A Database and Biorepository (MAGIC)
A Database and Biorepository for Mount Sinai Acute Graft-versus-Host Disease International Consortium (MAGIC)
- Patients undergoing an allogeneic hematopoietic stem cell transplant.
- Patients must have signed the informed consent document
- Syngeneic donor hematopoietic stem cell transplantation (HCTs) will be excluded.
A Pilot Study of APG-157 with Bevacizumab for Patients with Recurrent High-Grade Glioma
Treatment of Patients With Recurrent High-Grade Glioma With APG-157 and Bevacizumab
1. Patients must have pathologically proven diagnosis of high grade (aka grade III or IV) glioma that has progressed on bevacizumab (anaplastic astrocytoma, anaplastic
oligodendroglioma, glioblastoma, gliosarcoma, H3K27M mutant glioma).
2. Patients must have received prior radiation therapy and standard temozolomide. Patients who have received any number of therapies for previous progressions will be
considered eligible.
3. Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.
4. Physiologic Status/Age: Patients must be 19 years of age or older (the age of consent in Nebraska.)
5. Patients must have recovered from any toxicity of prior therapy to Grade 1 or less.
6. ECOG Performance Status of 0-3.
7. Patients must have an adequate bone marrow reserve (ANC count ≥ 1,500/mm^3, hemoglobin > 8 g/dL, platelet count ≥100,000/mm^3).
8. Patients must have adequate renal and hepatic function with:
1. creatinine < 1.5 x institutional upper limit of normal (ULN);
2. total bilirubin < 1.5 x ULN (unless due to Gilbert's disease);
3. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN;
4. serum alkaline phosphatase less than 2.5 times the upper limits of normal).
9. The patient must willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives,
potential benefits, side-effects, risks, and discomforts.
10. Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment.
11. Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study. (Non-child bearing potential is defined as age 55 years or older and
no menses for two years or any age with surgical removal of the uterus and/or both ovaries).
1. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of oral APG-157, or put the study outcomes at undue risk
2. Immunotherapy, chemotherapy, radiotherapy, or experimental therapy within one full cycle period before first dose of study drug (i.e., for lomustine 6 weeks, for
temozolomide 4 weeks).
3. Lactating or pregnant.
4. History of uncontrollable allergic reactions to bevacizumab.
5. Clinically Significant Cardiovascular Disease Defined as follows:
- Inadequately controlled hypertension (i.e., systolic blood pressure (SBP) > 160 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg despite antihypertensive therapy);
- History of cerebrovascular accident (CVA) within 6 months;
- Myocardial infarction or unstable angina within 6 months.
6. Evidence or history of bleeding diathesis (greater than normal risk of bleeding; i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > Grade 3 within 4
weeks prior to registration.
Note: Patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks.
7. Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture.
8. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration.
9. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to registration.
10. Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/4/23. Questions regarding updates should be directed to the study team contact.
Biomarkers for parkinsonian disorders in CNS-originating extracellular vesicles
Biomarkers for Parkinsonian Disorders From CNS-Originating Extracellular Vesicles
- Possible or Probable MSA (regardless of type).
- At least one other supporting test (CSF, imaging, RT-QuIC, smell test, autonomic testing). Does not have to be uniform but at least one supporting test is required. If any additional information supporting the diagnosis is available, please add to the accompanying data.
- N/A
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 2/28/23. Questions regarding updates should be directed to the study team contact.
Post-Operative Mobility after Operative Fixation of Geriatric Distal Femur Fractures: Which Construct Gives Patients More Independence?
Post-Operative Mobility after Operative Fixation of Geriatric Distal Femur Fractures
- Patients ≥ 60 years old who sustain a low energy distal femur fracture (AO-OTA 33A-C) and can give informed consent will be included.
- Patients with neuromuscular pathology that precludes safe or normal ambulation, metastatic disease, major psychiatric illness, or active drug or alcohol abuse.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 8/22/23. Questions regarding updates should be directed to the study team contact.
Trial Evaluating the Immunogenicity and Safety of an Adjuvanted Epstein-Barr Virus (EBV) Glycoprotein 350 Vaccine in EBV-seronegative Persons
• INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged 18 to 22 years.
• Able to provide informed consent.
• Willing to allow samples and data to be stored for future secondary research.
• Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months).
• In good general health as evidenced by medical history, physical examination, and laboratory screening results.
• Willing to forgo receipt of a licensed, live vaccine in the 30 days before and 30 days after each dose of the study vaccine. Any FDA-approved or authorized inactivated and/or protein subunit, RNA, or DNA vaccine can be used >=14 days before or >=14 days after administration of the study vaccine.
• Hemoglobin within institutional normal limits, or if not, then assessed and deemed not clinically significant by PI or designee.
• White blood cell count and differential within institutional normal reference range, or if not, then deemed not clinically significant by PI or designee.
• Total lymphocyte count (lymphocyte absolute) >800 cells/microliters.
• Platelet count of 125,000 to 500,000/microliters.
• Alanine aminotransferase <1.25 x upper limit of normal.
• Participants who can get pregnant must agree to abstain from sexual activities that can result in pregnancy or use one of the following effective methods of contraception, starting 30 days before the first dose of study vaccine through 60 days after the third dose:
• Intrauterine device (IUD) or equivalent.
• Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy before the first dose of study agent). If the participant uses a contraceptive pill, patch, or ring, then a barrier method (eg, internal/external condom, cervical cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
• A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy.
• Barrier method (eg, internal/external condom, cervical cap, or diaphragm) plus spermicide used correctly during sexual intercourse.
• A vasectomy in their monogamous sexual partner completed at least 6 months before the first dose of study vaccine.
• Continuous abstinence. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant or breastfeeding, or planning to become pregnant while participating through 60 days after the third dose of study vaccine.
• Has received any of the following: -- More than 10 days of systemic glucocorticoids (>=10 mg of prednisone or equivalent) within the 30 days prior to first dose of study agent.
• More than 10 days of systemic immunosuppressive medications, cytotoxic medications, or immunomodulating therapy within 180 days prior to first dose of study agent.
• Blood products, including immunoglobulins, within 120 days prior to first dose of study agent.
• Any live attenuated vaccination within 30 days prior to first dose of study agent.
• Investigational research agents within 30 days prior to first dose or planning to receive investigational products while on study.
• Allergy treatment with antigen injections, unless on a maintenance schedule of shots no more frequently than once per month.
• Has any of the following:
• Febrile illness within 14 days of the first dose of study agent.
• Body habitus such that identification of the deltoid muscle and/or administration of vaccine into the deltoid would be compromised or if body habitus would make study inclusion not in the best interest of the participant.
• History of serious reactions to vaccines.
• Hereditary, acquired, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Asthma that is not well-controlled or that required emergency care, urgent care, hospitalization, or intubation during the past 2 years, or that requires the use of oral or intravenous steroids.
• Diabetes mellitus type 1 or type 2, excluding a history of gestational diabetes.
• Clinically significant autoimmune disease or immunodeficiency.
• Bleeding disorder diagnosed by doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• Significant bruising or bleeding difficulties with intramuscular injections or blood draws.
• Malignancy that is active or treated malignancy for which there is no reasonable assurance of sustained cure or malignancy that is likely to recur during the study period.
• Seizure disorder other than a history of 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the past 3 years.
• Asplenia, functional asplenia, or any condition resulting in absence or removal of the spleen.
• History of Guillain-Barre Syndrome.
• Alcohol or drug abuse or addiction.
• HIV infection.
• Active hepatitis B or C infection.
• Documented EBV infection.
• Prior enrollment in an EBV vaccine clinical trial.
• Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation or impairs the participant s ability to give informed consent. Co-enrollment guidelines: Co-enrollment in other studies is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the PI or sponsor medical monitor (SMM). Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the PI or SMM.
A Study of Ponsegromab in People With Heart Failure (GARDEN TIMI 74)
• Male and female participants aged 18 years or older -. Clinical evidence of HF with each of the following criteria: 1. LVEF <50% on most recent measurement, within 12 months of screening. Note: An assessment of LVEF in the prior 12 months is not required in situations where LVEF has been persistently <50% on prior assessments obtained at least 3 months apart (including the most recent measurement). 2. NYHA class II-IV at screening. 3. Main cohort only: NT-proBNP ≥400 pg/mL at screening.
• Serum GDF-15 concentration ≥2000 pg/mL at screening.
• Main cohort only: KCCQ-23 CSS <75 at screening.
• Main cohort only: Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening: 1. Non-edematous unintentional weight loss ≥5% in the last 6 months or current BMI <20 kg/m2, associated with subjective fatigue or anorexia; or 2. Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks based on the KCCQ-23 administered at screening; or 3. A score of <60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.
• Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
• Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial. For the open-label, PK cohort only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.
• History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
• Acute coronary syndrome within 1 month prior to randomization.
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial. For the open-label, PK cohort only: coronary revascularization more than 1 month prior to randomization is permitted.
• Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
• Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
• Previous exposure to ponsegromab in a prior clinical study.
• Renal disease requiring ongoing dialysis.
• Cirrhosis with evidence of portal hypertension not due to HF, or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN, or total bilirubin level ≥ 2 x ULN (unless history of Gilbert's syndrome).
Pelvic Fixation and Fusion During Multilevel Spinal Surgery (PAULA)
Study of ONCOFID-P-B (PACLITAXEL-HYALURONIC ACID)
• At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy.
• At least five of six doses of an initial induction course plus at least two of six doses of a second induction course. 5. Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable, obvious areas of CIS should also be fulgurated). 1. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers. 2. In patients undergoing transurethal resection of their bladder tumors, absence of locally advanced disease should be confirmed by pelvic examination under anesthesia. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 7. Adequate organ function: absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 10.0 g/dL, ALT/AST ≤1. 5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN, total serum bilirubin ≤ 1.5 x ULN, serum creatinine ≤ 2.2 mg/dL. 8. Women in non-reproductive years (defined as surgically sterile or one year postmenopausal). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test upon entry into this study and agree to use highly effective contraceptive methods, i.e. methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
• oral
• injectable
• implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner (*)
• sexual abstinence (**) 9. Male patients with WOCBP partners must agree to use effective contraceptive methods, i.e.:
• condom;
• consider contraception for non-pregnant WOCBP partner. 10. Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol. (*) Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. (**) Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated to the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
North American Prodromal Synucleinopathy Consortium Stage 2 (NAPS2)
Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial
• Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NAT test [list of approved tests in the PIM] within 14 days of randomization.
• Requiring hospitalization for the management of COVID-19
• Has evidence of COVID-19 pneumonia (PNA) defined as either receiving supplementary oxygen ≤2L of low flow oxygen with evidence of airspace disease on chest imaging (X ray, computer tomography or ultrasound) OR receiving supplementary oxygen >2L and <10 L of low flow oxygen.
• Currently receiving or planned to receive (ordered) one IM drug (for example, a corticosteroid or baricitinib) as part of treatment of COVID-19 prior to randomization.
• Has started supplemental oxygen for the treatment of COVID-19 within the past 5 calendar days. Patients on home oxygen are eligible if current oxygen flow rate is increased from baseline and other above criteria are met.
• Investigator agrees that the pneumonia is due to COVID-19.
• Oxygen requirement of ≥10L or more of low flow oxygen (or equivalent if using Venturi mask, etc), or requiring either HFNO, NIV, IMV, or ECMO.
• Participant has received more than one baseline IM for treatment of the current COVID-19 infection at time of trial enrollment. (Examples: corticosteroid, baricitinib, tocilizumab, anakinra, abatacept, or infliximab.)
• Participant anticipated to not meet all inclusion criteria within 24 hours of randomization in the opinion of the investigator.
• Allergy to investigational agent.
• Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 10 3 /μL or <1.0 G/L) on most recent lab within 2 calendar days of randomization.
• Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 10 3 /μL or <0.20 G/L) on most recent lab within 2 calendar days of randomization.
• Known or suspected active or recent serious infection (bacterial, fungal, viral, or parasitic infection, excepting SARS-CoV-2) that in the opinion of the investigator could constitute a risk when taking investigational agent. Note: Broad spectrum empiric antibiotic usage does not exclude participation.
• Known or suspected history of untreated tuberculosis (TB). TB diagnosis may be suspected based on medical history and concomitant therapies that would suggest TB infection. Participants are also excluded if they have known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
• Have received any live vaccine (or live attenuated) within 3 months before screening or intend to receive a live vaccine (or live attenuated) during the trial. Use of prior non-live (inactivated) vaccinations is allowed for all participants, including any vaccine for COVID-19.
• Pre-existing immunomodulation or immunosuppression that meets any of the following: Participant has received abatacept for an indication other than COVID- 19 within 5 half-lives (65 days) of enrollment (Abatacept elimination half-life is 13.1 days.) Participant is receiving immune modulatory therapy for autoimmune, transplant management or another indication AND has one or more of the following: evidence of active infection (other than COVID-19) or has required reduction in their immune modulatory therapy in the preceding 6 months due to infectious complication (routine reduction as SOC is not an exclusion) or has required intensification in immunotherapy within the preceding 6 months due to organ rejection/worsening underlying disease status (e.g., intensification with an additional agent on top of usual immunosuppressive regimen)
• Participant has recently received or is anticipated to require immune modulatory agents for their underlying disease including chemotherapeutic treatments likely to induce neutropenia (<1.0 x 10 9 cells/µL) or lymphopenia (<1.0 x 10 9 cells/µL)
• Participant has untreated advanced HIV (known CD4 <200 in the past 6 months) AND is not established on antiretroviral therapy
• Pregnancy
• Breastfeeding
• Co-enrollment in other trials not predetermined to be compatible with this trial.
• In the investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.
• The treating clinician expects inability to participate in trial procedures or participation would not be in the best interests of the patient.
Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty
The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD) (MDD)
• Did not respond or have insufficiently responded by less than 50% improvement; dose and duration defined & rated at minimum confidence level 3 on the ATRF;
• Did not respond or has insufficiently responded to at least one but no more than four adequate trials of antidepressant medications (4 ≥ ATRF ≥1) or
• Did not respond or has insufficiently responded due to poor tolerability to at least two inadequate antidepressant medication trials (ATIF ≥2). 6. Subject must be on at least one (1) antidepressant medication (minimum therapeutic dose not required if tolerability precluded further dose titration) and is willing to remain on the same daily dose of antidepressant medication(s) for a minimum of 28 days prior to randomization and thereafter for the duration of the study. 7. For subjects receiving current depression focused psychotherapy: psychotherapy initiated at least 1 month prior to baseline visit with a stable frequency of visits regimen, in the opinion of the Investigator. 8. Subject is able to provide written Informed Consent and is capable of complying with the specified study requirements, as determined by the Investigator. 9. Subject has cognitive and/or motor skills needed to operate a smartphone and can be contacted by phone, as determined by the Investigator.
A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT (HURCULES)
A Study to Test Radium-223 With Docetaxel in Patients With Prostate Cancer
• Willing and able to provide written informed consent (ICF) and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Males 18 years of age and above
• Histological or cytological proof of prostate cancer
• Documented progressive mCRPC based on at least one of the following criteria: 1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 1.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 1.0 ng/mL. 2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the LD of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions. 3. Progression of bone disease (evaluable disease) or two or more new bone lesions by bone scan.
• Two or more bone lesions
• ECOG 0- 1
• Normal organ function with acceptable initial laboratory values within 14 days of randomization:
• Albumin > 30 g/L
• ANC ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100 x 10^9/L
• Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN)
• Bilirubin ≤ ULN (unless documented Gilbert's disease)
• SGOT (AST) ≤ 1.5 x ULN
• SGPT (ALT) ≤ 1.5 x ULN
• WBC count ≥ 3 x 10^9/L
• Subjects must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 30 days after the last dose of study drug. Sperm donation is prohibited during the study and for 30 days after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
• Serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy.
• All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less.
• Willing and able to comply with the protocol, including follow-up visits and examinations
• Received any other investigational therapeutic agents or other anticancer therapies within 4 weeks prior to randomization.
• Received external beam radiotherapy within the 4 weeks prior to randomization.
• Has an immediate need for external beam radiotherapy.
• Has received any systemic bone-seeking radiopharmaceutical in the past.
• Has received any prostate cancer directed chemotherapy in the castration resistant setting. Subjects who have received up to 6 prior doses of docetaxel in the castration sensitive setting are permitted if they have not experienced disease progression within 36 weeks of last treatment with docetaxel.
• Has received four or more systemic anticancer regimens for mCRPC.
• Treatment with docetaxel or abiraterone for non-castrate metastatic disease is permissible and does not count towards the lines of therapy for mCRPC
• A 'line' is a regimen. Combinations of hormones and other types of therapies count as single lines.
• Has known Grade ≥3 docetaxel-related toxicities or docetaxel toxicity related dose interruption or discontinuation.
• Has received blood transfusions or growth factors within the last 4 weeks prior to randomization.
• Symptomatic nodal disease (i.e., scrotal, penile, or leg edema).
• Has visceral metastases with ≥ 3 lung and/or liver metastases or individual lesion ≥2 cm, as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to randomization.
• Symptomatic loco-regional disease that causes ongoing Grade 3 or Grade 4 urinary or rectal symptoms.
• Subjects with a "currently active" second malignancy other than non-melanoma skin cancers or non-invasive bladder cancers or other in-situ or non-invasive malignancies. Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
• Has imminent or established cord compression based on clinical findings and/or MRI.
• Known bone marrow dysplasia
• Has received any of the following in the 4 weeks prior to randomization: 5-alpha-reductase inhibitors, herbal medications, natural hormonally active foods (e.g., phytoestrogens) or other food supplements known to alter PSA in humans
• Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including but not limited to:
• Uncontrolled infection
• NYHA III or IV heart failure
• Crohn's disease or those with ulcerative colitis who have not undergone a colectomy
• Known active infection with HIV, Hepatitis B or Hepatitis C
Prophylaxis Regimen for Hemophilia A Patients (PREDICT)
• Participants must be ≥ 12 years of age inclusive, at the time of signing the informed consent/assent.
• Previously treated patients (≥ 150 EDs) with congenital hemophilia A.
• Prophylaxis with any SHL FVIII product with a stable frequency for at least 6 consecutive months within the last 12 months prior to screening before entering the study and documented in medical records. Stable frequency is defined as a minimum 18 weeks of treatment in a 6 (consecutive) calendar month period in the 12 months prior to screening. Patients can be on any non-Jivi EHL between the 6-month stable SHL prophylaxis period and start of study treatment.
• Documented bleeding rate (ABR) while on stable frequency SHL prophylaxis for at least 6 consecutive months within the last 12 months prior to screening.
• No current evidence (≥ 0.6 BU/mL) of FVIII inhibitors. If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL on two occasions) but has been tolerized for at least 1 year since the last positive titer with at least 1 negative inhibitor assay test during that period, they can be enrolled. If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL) but did not require tolerization and has had at least 1 negative inhibitor assay test during a minimum period of at least 1 year since the last positive titer, they can be enrolled.
• If they are human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4+) lymphocyte count should be > 200/mm^3 within 1 year before entering the study and documented in medical records. -
• Participants who are willing to complete an electronic diary (eDiary).
• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• For adolescent participants (≥ 12 to < 18 years), a legal guardian must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day according to the Schedule of Activities (SoA) (e.g. able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the PROs during the scheduled study visits; accurately and reliably dispense study intervention as directed.
• For adolescent participants, a legal guardian must be able to accurately maintain the child's take-home record, including items of general health.
• Any other inherited or acquired bleeding disorder in addition to hemophilia A. Note: von Willebrand disease should be diagnosed per local clinical practice. Participants with a diagnosis of von Willebrand disease in medical records or diagnosed at the time of screening will be excluded.
• Platelet count < 100,000/mm^3
• Evidence of inhibitor to FVIII (≥ 0.6 BU/mL) within the last 1 year
• The participant is currently participating in another investigational drug study or has participated in a clinical study involving an investigational drug or device within 30 days of signing informed consent.
• The participant has a planned major surgery.
• Documentation of missing risk score parameters other than physical activity .
• Known hypersensitivity to the drug substance, excipients, or mouse or hamster protein.
• Any other significant medical condition that the investigator feels would be a risk to the participant or would impede the study.
• Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
• Otherwise vulnerable participants (e.g. participants who are in custody by order of an authority).
• Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures (i.e. eDiary completion, clinic visits, phone updates), restrictions, and requirements.
Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement (COMPLETE TAVR)
•Symptomatic aortic valve stenosis prior to TAVR (NYHA Functional Class ≥ 2 OR Abnormal exercise test with severe SOB, abnormal BP response, or arrhythmia) AND
•CAD defined as: at least 1 coronary artery lesion of ≥70% visual angiographic diameter stenosis in a native segment ≥2.5 mm in diameter that is not a CTO and is amenable to treatment with PCI AND
•Consensus by the Local Multidisciplinary Heart Team that the patient is suitable for elective transfemoral TAVR with a balloon expandable transcatheter heart valve AND would receive a bypass with an anastomosis distal to the coronary artery lesion(s) if they were undergoing SAVR. Local Multidisciplinary Heart Teams are expected to follow current clinical guidelines for selection of patients for TAVR with an eligible patient generally expected to have: [AVA ≤ 1.0 cm2 OR AVA index ≤ 0.6 cm2/m2] OR [Jet velocity ≥ 4.0 m/s OR mean gradient ≥ 40 mmHg] OR patients without these criteria may undergo TAVR if the Local Multidisciplinary Heart Team concludes it is appropriate. AND
•Successful transfemoral TAVR, defined as the implantation of a single transcatheter aortic valve within the past 96 hours with freedom from more than minimal aortic insufficiency, stroke, or major vascular complications.
• PCI already performed within 90 days prior to TAVR or at the same time as the index transfemoral TAVR procedure
• Planned PCI of coronary artery lesion(s)
• Planned surgical revascularization of coronary artery lesion(s)
• Non-cardiovascular co-morbidity reducing life expectancy to < 5 years
• Any factor precluding 5-year follow-up
• Prior coronary artery bypass grafting surgery or surgical valve replacement
• Severe mitral regurgitation (> 3+)
• Severe left ventricular dysfunction (LVEF < 30%)
• Low coronary takeoff (high risk for coronary obstruction)
• Acute myocardial infarction within 90 days
• Stroke or transient ischemic attack within 90 days
• Renal insufficiency (eGFR < 30 ml/min) and/or renal replacement Rx
• Hemodynamic or respiratory instability