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

• ClinicalTrials.gov Identifier: NCT03406780
• Recruitment Status: Completed
• First Posted: January 23, 2018
• Last Update Posted: June 5, 2020
• Sponsor: Capricor Inc.
• Information provided by (Responsible Party): Capricor Inc.

Tracking Information

• First Submitted Date: January 15, 2018
• First Posted Date: January 23, 2018
• Last Update Posted Date: June 5, 2020
• Actual Study Start Date: March 4, 2018
• Actual Primary Completion Date: March 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2018)

Change in the mid-level (elbow) dimension of the Performance of the Upper Limb (PUL) [ Time Frame: Month 12 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 19, 2018)

• Change in the mid-level (elbow) dimension of the PUL [ Time Frame: Months 3, 6, and 9 ]
  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.
• Change in regional systolic left ventricular wall thickening as assessed by cardiac MRI [ Time Frame: Months 6 and 12 ]
  Systolic thickening is thought to be a principal mechanism of cardiac output generation in people with DMD.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne
• Muscular Disorders, Atrophic
• Muscular Diseases
• Neuromuscular Diseases
• Nervous System Diseases
• Genetic Diseases, X-Linked
• Genetic Diseases, Inborn

Intervention

• 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
• Drug: Placebo
  Placebo

Study Arms

• Experimental: CAP-1002
  Patients will receive 150 million cardiosphere-derived cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses.
  Intervention: Biological: CAP-1002
• Placebo Comparator: Placebo
  Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses.
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2019): 18
• Original Estimated Enrollment (submitted: January 19, 2018): 84
• Actual Study Completion Date: March 10, 2020
• Actual Primary Completion Date: March 10, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 10 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03406780
• Other Study ID Numbers: CAP-1002-DMD-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Capricor Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Capricor Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Craig McDonald, MD; University of California, Davis

• PRS Account: Capricor Inc.
• Verification Date: June 2020