HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne)

NCT02485938 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CAP-1002-DMD-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Duchenne Muscular Dystrophy; Cardiomyopathy

Keywords

Duchenne Muscular Dystrophy; Cardiomyopathy

Outcome Measures

Primary Outcomes (15)

• Number of Participants Experiencing Any of the Adjudicated Events

  Adjudicated Events reported included: New thrombolysis in myocardial infarction (TIMI) flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2noted immediately following infusion and persisting greater than (\>) 3 minutes, despite intracoronary vasodilator administration; sudden unexpected death within 72 hours of intracoronary infusion; and Major adverse cardiac event (MACE) within 72 hours of intracoronary infusion, including death, non-fatal myocardial infarction and hospitalization for cardiovascular event (including heart failure hospitalizations).

  Within 72 hours post-infusion

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that occurred or worsened in severity between the first dose of the investigational medicinal product (IMP) until the end of study. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.

  Up to Month 12 post-infusion

• Change From Baseline in Clinical Laboratory Parameters (Chloride, Potassium and Sodium) at Month 6 and Month 12

  Clinical chemistry parameters assessed were chloride, potassium and sodium.

  Baseline, Month 6 and Month 12

• Change From Baseline in Clinical Laboratory Parameter - Albumin at Month 6 and Month 12

  Clinical chemistry parameter assessed was albumin.

  Baseline, Month 6 and Month 12

• Change From Baseline in Clinical Laboratory Parameter - Glucose at Month 6 and Month 12

  Clinical chemistry parameter assessed was glucose.

  Baseline, Month 6 and Month 12

• Change From Baseline in Hematological Parameters (Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Month 6 and Month 12

  Hematological parameters assessed were: platelets, white blood cells, basophils, eosinophils, lymphocytes, monocytes and neutrophils.

  Baseline, Month 6 and Month 12

• Change From Baseline in Hematological Parameter - Hemoglobin at Month 6 and Month 12

  Hematological parameter assessed was hemoglobin.

  Baseline, Month 6 and Month 12

• Change From Baseline in Hematological Parameter - Red Blood Cells at Month 6 and Month 12

  Hematological parameter assessed was red blood cells.

  Baseline, Month 6 and Month 12

• Change From Baseline in Vital Signs - Blood Pressure at Month 6 and Month 12

  Vital signs assessed were systolic and diastolic blood pressure.

  Baseline, Month 6 and Month 12

• Change From Baseline in Vital Signs - Heart Rate at Month 6 and Month 12

  Vital signs assessed was heart rate.

  Baseline, Month 6 and Month 12

• Change From Baseline in Vital Signs - Respiratory Rate at Month 6 and Month 12

  Vital signs assessed was respiratory rate.

  Baseline, Month 6 and Month 12

• Change From Baseline in Vital Signs - Temperature at Month 6 and Month 12

  Vital signs assessed was temperature.

  Baseline, Month 6 and Month 12

• Number of Participants With Clinically Significant Change From Baseline in Cardiac Physical Examinations at Month 6 and Month 12

  Cardiac physical examination parameters assessed were: jugular vein distension, edema, heart sounds, murmur, breath sounds.

  Baseline, Month 6 and Month 12

• Change From Baseline in Electrocardiogram (ECG) Parameters (QRS Duration, PR, QT, QTc and QT Interval) at Month 6 and Month 12

  ECG parameters assessed were: PR Interval, QRS Duration, QT Interval, QTc interval and QT interval.

  Baseline, Month 6 and Month 12

• Change From Baseline in Electrocardiogram Parameter - Ventricular Rate at Month 6 and Month 12

  ECG parameter assessed was ventricular rate; which depends on the degree of atrioventricular conduction.

  Baseline, Month 6 and Month 12

Other Outcomes (31)

• Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12

  Baseline, Month 6 and Month 12

• Percent Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12

  Baseline, Month 6 and Month 12

• Absolute Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12

  Baseline, Month 6 and Month 12

Study Arms (2)

Allogeneic Cardiosphere-Derived Cells (CAP-1002)

EXPERIMENTAL

CAP-1002 is an investigational product consisting of allogeneic cardiosphere-derived cells (CDCs). All subjects assigned to the active treatment arm will receive an intended total dose of 75 million (M) CAP-1002 cells infused as 25M cells into each of the three left ventricle cardiac territories (anterior, lateral, inferior/posterior). If any of the three coronary arteries are deemed by the infusing Investigator to supply less than 30% of the left ventricular myocardium, the infusing Investigator may choose to infuse only 12.5M cells into that coronary artery or arteries. Therefore the full dose of CAP-1002 delivered may range from 50M cells to 75M cells provided that all three arteries are infused.

Drug: Allogeneic Cardiosphere-Derived Cells (CAP-1002)

Usual Care

NO INTERVENTION

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

Interventions

Allogeneic Cardiosphere-Derived Cells (CAP-1002) DRUG

Intracoronary delivery of Allogeneic Cardiosphere-Derived Cells (CAP-1002)

Also known as: CAP-1002

Allogeneic Cardiosphere-Derived Cells (CAP-1002)

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Documented diagnosis of Duchenne Muscular Dystrophy by genetic mutation analysis.
• 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.
• 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.
• Participants must be taking systemic glucocorticoids for at least six months prior to screening.
• Participants must be 12 years of age or older at time of screening
• Participants must be appropriate candidates for cardiac catheterization and intracoronary infusion of CAP-1002, in the judgement of the site's interventional cardiologist.

You may not qualify if:

• Therapy with intravenous inotropic or vasoactive medications at the time of screening.
• Inability to undergo cardiac catheterization and/or MRI without general anesthesia.
• Immunologic incompatibility with all available Master Cell Banks (MCBs) by single-antigen bead (SAB) serum antibody profiling.
• Planned or likely major surgery in the next 12 months after planned randomization.
• Left Ventricular Assist Devices (LVAD) or those subjects actively in the process of acquiring a LVAD.
• Contraindication to cardiac MRI.
• Known hypersensitivity to contrast agents.
• Estimated glomerular filtration rate (GFR) \<60 mL/min, as calculated by the CKD-EPI cystatin C equation (Inker, Schmid et al. 2012).
• Active infection not responsive to treatment.
• Active systemic allergic reaction(s), connective tissue disease or autoimmune disorder(s).
• History of cardiac tumor or cardiac tumor demonstrated on screening MRI.
• History of previous stem cell therapy.
• 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.
• Known moderate-to-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation.
• Current active alcohol or drug abuse.

Sponsors & Collaborators

• Capricor Inc.: lead

Study Sites (3)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Cardiomyopathies

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Vice President of Clinical Research and Development Operations
• Organization: Capricor, Inc.

clinicaltrialsgov@capricor.com

858-727-1755

Study Officials

• Mark Awadalla

  Capricor Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2015
• First Posted: June 30, 2015
• Study Start: January 7, 2016
• Primary Completion: September 14, 2017
• Study Completion: September 14, 2017
• Last Updated: January 9, 2025
• Results First Posted: January 9, 2025

Record last verified: 2025-01

Locations

US (3)