A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy (HOPE-2)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects With Duchenne Muscular Dystrophy

HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne muscular dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.

Study Overview

• Status: Completed
• Conditions: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Diseases; Neuromuscular Diseases; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Dystrophy, Duchenne
• Intervention / Treatment: Drug: Placebo; Biological: CAP-1002

Detailed Description

• Approximately 84 eligible study participants will be randomized to either CAP-1002 or placebo in a 1:1 ratio.
• The trial will include visits at Screening, Baseline/Day 1, Week 4, and Months 3, 6, 9, and 12 with IV infusions of CAP-1002 or placebo on Day 1 and Months 3, 6, and 9.
• Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead ECG, and clinical laboratory testing.
• Efficacy will be evaluated in the Performance of the Upper Limb, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, cardiac MRI, and quality of life.
• If trial data suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension study to offer CAP-1002 to study participants who were randomized to placebo and completed all trial visits during the 12-month period.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Genetically confirmed DMD
2. Reduced upper arm strength as measured by the Performance of Upper Limb
3. Reduced ability to walk/run (if ambulatory)
4. Treatment with systemic glucocorticoids for at least 12 months and at a stable dose at least 6 months prior to study participation, except for weight-based or toxicity-related adjustments
5. Current and up-to-date immunizations

Exclusion Criteria:

1. Left ventricular ejection fraction < 35%
2. BMI > 45
3. Ambulant if ≥ 18 years of age
4. Exon 44 skip-amenable mutation(s) in the DMD gene
5. Deletion mutation(s) encompassing exons 3-7 of the DMD gene
6. Percent-predicted forced vital capacity (FVC) < 35%
7. Chronic respiratory disease not related to DMD (for example, asthma, bronchitis, and tuberculosis)
8. History of diabetes requiring treatment with metformin or insulin within 3 months prior to randomization
9. Treatment with an FDA-approved exon skipping therapy for the treatment of DMD if on a stable dose for less than 24 months prior to randomization
10. Treatment with human growth hormone (HGH) within 3 months prior to randomization, unless on a stable dose for at least 24 months prior to randomization
11. Treatment with idebenone within 3 months prior to randomization
12. Treatment with a cell therapy product within 12 months prior to randomization
13. Treatment with an investigational product within 6 months prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAP-1002; Patients will receive 150 million cardiosphere-derived cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses.	Biological: CAP-1002; The active pharmaceutical ingredient in CAP-1002 is Cardiosphere-Derived Cells (CDCs). CDCs are known to secrete numerous bioactive elements (growth factors, exosomes) which impact the therapeutic benefits of the cell-based therapy. The mechanism of action is the composite ability to be immunomodulatory, anti-fibrotic and regenerative.; Other Names: Cardiosphere-Derived Cells; CDCs
Placebo Comparator: Placebo; Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the mid-level (elbow) dimension of the Performance of the Upper Limb (PUL)	The PUL includes functional tasks that relate to activities of daily living that are very important for quality of life. The PUL has been validated for the assessment of upper limb motor function in individuals with DMD.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the mid-level (elbow) dimension of the PUL	The PUL includes functional tasks that relate to activities of daily living that are very important for quality of life. The PUL has been validated for the assessment of upper limb motor function in individuals with DMD.	Months 3, 6, and 9
Change in regional systolic left ventricular wall thickening as assessed by cardiac MRI	Systolic thickening is thought to be a principal mechanism of cardiac output generation in people with DMD.	Months 6 and 12

Collaborators and Investigators

• Sponsor: Capricor Inc.

Publications and helpful links

General Publications

• McDonald CM, Marban E, Hendrix S, Hogan N, Ruckdeschel Smith R, Eagle M, Finkel RS, Tian C, Janas J, Harmelink MM, Varadhachary AS, Taylor MD, Hor KN, Mayer OH, Henricson EK, Furlong P, Ascheim DD, Rogy S, Williams P, Marban L; HOPE-2 Study Group. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022 Mar 12;399(10329):1049-1058. doi: 10.1016/S0140-6736(22)00012-5.

Helpful Links

• Company website

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2018
• Primary Completion (Actual): March 10, 2020
• Study Completion (Actual): March 10, 2020

Study Registration Dates

• First Submitted: January 15, 2018
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Cell Therapy; Pulmonary Function; Duchenne Muscular Dystrophy; Glucocorticoids; Ambulatory; Non-Ambulatory; Performance of the Upper Limb
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Dystrophies; Nervous System Diseases; Muscular Diseases; Muscular Dystrophy, Duchenne; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Neuromuscular Diseases; Muscular Disorders, Atrophic
• Other Study ID Numbers: CAP-1002-DMD-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No