Clinical trial NCT02485938: HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne)
Official title: A Randomized, Open-label Study of the Safety and Efficacy of Multi- Vessel Intracoronary Delivery of Allogeneic Cardiosphere-Derived Cells in Patients With Cardiomyopathy Secondary to Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Cardiomyopathy
Keywords: Duchenne Muscular Dystrophy
Cardiomyopathy
Lead sponsor: Capricor Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 25
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Male participants with cardiomyopathy secondary to Duchenne muscular dystrophy (DMD) meeting all inclusion and no exclusion criteria will be randomized. All participants will be at least 12 years of age. They will be randomized in a 1:1 manner to either intracoronary infusion of CAP-1002 in three coronary arteries supplying the three major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or usual care. In the active treatment arm, all three major cardiac territories will be treated (infused) during a single procedure in an open-label fashion.

Detailed description: Approximately 24, and not more than 30, participants will be randomized into the study, in two sequential enrollment groups. Safety data from Group 1 will undergo a Data Safety Monitoring Board (DSMB) review prior to initiation of enrollment for Group 2.

The first 6-8 randomized participants will comprise Group 1, and will include a minimum of 3 participants completing intracoronary infusion with CAP-1002. The DSMB will conduct a review of interim safety data through 72 hours post-Day 0 for at least 3 infused participants and for at least 6 participants overall.

Enrollment of Group 2 will begin per DSMB recommendations following their review of the 72 hour safety data from Group 1. Group 2 will include approximately 18 participants. Screening and randomization will continue until at total of 12 participants are infused with CAP 1002 or 30 participants are randomized into the study, whichever comes first.

All participants assigned to the active treatment arm will receive an intended total dose of up to 75 million (M) CAP-1002 cells infused as 25M cells into each of the three left ventricle cardiac territories (anterior, lateral, inferior/posterior).

Participants randomized to receive usual care will continue to be cared for and treated in whatever manner the investigator deems most appropriate for the participant on an ongoing basis, and will receive no infusion.

Randomization will take place within 30 days of the first screening procedure. After completion of the screening procedures, eligible participants randomized to active treatment arm will receive CAP-1002 administered via intracoronary infusion on Day 0. Day 0 for eligible participants randomized to the usual care arm will occur 7 days after the date of randomization. All randomized participants will have a follow-up telephone call on Study Day 3, and study visits at Weeks 2 and 6, and at Months 3, 6 and 12 post Day 0.

Eligibility criteria: Inclusion Criteria:

1. Male participants 18 years of age or older must be able to provide informed consent and follow up with protocol procedures. Male participants at least 12 years of age but younger than 18 years of age must be able to provide assent with parent or guardian providing permission for study participation. Only male participants will be randomized into this study.
2. Documented diagnosis of Duchenne Muscular Dystrophy by genetic mutation analysis.
3. Cardiomyopathy with left ventricular scar by late gadolinium enhancement (LGE) in at least 4 segments as assessed by contrast-enhanced MRI and EF \>35% at the time of screening.
4. Use of evidence based medical-therapy in accordance with the "DMD Care Considerations Working Group" guidelines for the management of DMD, for at least three months prior to signing the consent form (or, providing assent) or documented contraindication or intolerance or patient preference.
5. Participants must be taking systemic glucocorticoids for at least six months prior to screening.
6. Participants must be 12 years of age or older at time of screening
7. Participants must be appropriate candidates for cardiac catheterization and intracoronary infusion of CAP-1002, in the judgement of the site's interventional cardiologist.

Exclusion Criteria:

1. Therapy with intravenous inotropic or vasoactive medications at the time of screening.
2. Inability to undergo cardiac catheterization and/or MRI without general anesthesia.
3. Immunologic incompatibility with all available Master Cell Banks (MCBs) by single-antigen bead (SAB) serum antibody profiling.
4. Planned or likely major surgery in the next 12 months after planned randomization.
5. Left Ventricular Assist Devices (LVAD) or those subjects actively in the process of acquiring a LVAD.
6. Contraindication to cardiac MRI.
7. Known hypersensitivity to contrast agents.
8. Estimated glomerular filtration rate (GFR) \<60 mL/min, as calculated by the CKD-EPI cystatin C equation (Inker, Schmid et al. 2012).
9. Active infection not responsive to treatment.
10. Active systemic allergic reaction(s), connective tissue disease or autoimmune disorder(s).
11. History of cardiac tumor or cardiac tumor demonstrated on screening MRI.
12. History of previous stem cell therapy.
13. History of use of medications listed in Appendix 3 within 3 months prior to signing the Inform Consent Form / Assent through completion of the study infusion.
14. Known moderate-to-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation.
15. Current active alcohol or drug abuse.
16. Known history of Human Immunodeficiency Virus (HIV) infection.
17. Known history of chronic viral hepatitis.
18. Abnormal liver function (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \>10 times the upper reference range) and/or abnormal hematology (hematocrit \<25%, White Blood Cells \<3000 μl, platelets \<100,000 μl) studies without a reversible, identifiable cause.
19. Known hypersensitivity to bovine products.
20. Known hypersensitivity to dimethyl sulfoxide (DMSO).
21. Uncontrolled diabetes (HbA1c \>9.0).
22. Inability to comply with protocol-related procedures, including required study visits.
23. Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for the study.
24. Currently receiving investigational treatment on another clinical study or expanded access protocol, including any of the following:

    * Received investigational intervention within 30 days prior to randomization
    * Treatment and/or an incomplete follow-up to treatment with any investigational cell based therapy within 6 months prior to randomization
    * Active participation in other research therapy for cardiovascular repair/regeneration

Primary outcomes:
measure: Number of Participants Experiencing Any of the Adjudicated Events
timeFrame: Within 72 hours post-infusion
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Month 12 post-infusion
measure: Change From Baseline in Clinical Laboratory Parameters (Chloride, Potassium and Sodium) at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Clinical Laboratory Parameter - Albumin at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Clinical Laboratory Parameter - Glucose at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Hematological Parameters (Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Hematological Parameter - Hemoglobin at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Hematological Parameter - Red Blood Cells at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Vital Signs - Blood Pressure at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Vital Signs - Heart Rate at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Vital Signs - Respiratory Rate at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Vital Signs - Temperature at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Number of Participants With Clinically Significant Change From Baseline in Cardiac Physical Examinations at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Electrocardiogram (ECG) Parameters (QRS Duration, PR, QT, QTc and QT Interval) at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Electrocardiogram Parameter - Ventricular Rate at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
Secondary outcomes:
Other outcomes:
measure: Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in LV Late Gadolinium Enhancement (LGE) Scar Tissue Mass at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in LV Late Gadolinium Enhancement (LGE) Scar Tissue Mass at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Left Ventricular (LV) Late Gadolinium Enhancement (LGE) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Percent Change From Baseline in LV Late Gadolinium Enhancement (LGE) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Absolute Change From Baseline in Circumferential Strain at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Circumferential Strain at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Function of the Region Receiving CAP-1002 Therapy at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Function of the Region Receiving CAP-1002 Therapy at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Performance of the Upper Limb (PUL) Overall Score (Excluding Shoulder) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Performance of the Upper Limb (PUL) Overall Score (Including Shoulder) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Peak Expiratory Flow (PEF) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Percent Predicted Peak Expiratory Flow at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Percent Predicted Forced Vital Capacity Level at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Forced Vital Capacity (FVC) Levels at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Forced Expiratory Flow at 25-75% of FVC (FEF25-75%) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Percent Predicted Forced Expiratory Flow at 25-75% of FVC at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Forced Expiratory Time (FET) at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Six-Minute Walk Test at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Summary Score - Participant Responses at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Pediatric Quality of Life Inventory Total Summary Score - Parent Responses at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Score - Parent Responses at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Score - Participant Responses at Month 6 and 12
timeFrame: Baseline, Month 6 and 12
measure: Change From Baseline in Duchenne Muscular Dystrophy Biomarkers at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Capricor Inc.
name: Mark Awadalla
role: STUDY_DIRECTOR
References: