A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy (HOPE-3)

• ClinicalTrials.gov Identifier: NCT05126758
• Recruitment Status: Recruiting
• First Posted: November 19, 2021
• Last Update Posted: January 11, 2023
• Sponsor: Capricor Inc.
• Information provided by (Responsible Party): Capricor Inc.

Study Description

Brief Summary:

HOPE-3 is a multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne muscular dystrophy (DMD) and impaired skeletal muscle function. 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. All participants will be eligible to receive CAP-1002 for an additional 12 months as part of an open label extended assessment period.

Condition or disease	Intervention/treatment	Phase
Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Nervous System Diseases	Biological: CAP-1002; Drug: Placebo	Phase 3

Detailed Description:

Up to 68 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.

The primary analysis of efficacy and safety will be performed at Month 12 following 4 administrations of CAP-1002 or placebo.

The primary efficacy endpoint is the mean change from baseline in upper limb function as assessed by the full Performance of the Upper Limb test, version 2.0 [PUL 2.0] at the 12-month time point. Secondary endpoints evaluated at the 12-month time point include assessment of changes in cardiac muscle function and structure by cardiac magnetic resonance imaging [cMRI], changes in hand-to-mouth function [eat 10-bites assessed by the Duchenne Video Assessment (DVA)], and quality of life assessments.

Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, and clinical laboratory testing.

Following the initial 4 infusions, all subjects will be eligible to participate in a 12-month open label extended assessment period and receive up to 4 additional IV infusions of CAP-1002 once every 3 months. An analysis of extended safety and efficacy will be conducted after all subjects have completed the Month 24 visit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Human Allogeneic Cardiosphere-Derived Cells for the Treatment of Duchenne Muscular Dystrophy
• Actual Study Start Date: June 22, 2022
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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; CAP-1002 is a cell therapy consisting of human allogeneic 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in full upper limb function [ Time Frame: At Month 12 ]
   Mean change from baseline in full Performance of the Upper Limb test, version 2 (PUL 2.0). items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation

Secondary Outcome Measures :

1. Change in cardiac muscle function and structure by assessment of left ventricular ejection fraction [ Time Frame: At Month 12 ]
   Mean change from baseline in left ventricular ejection fraction as assessed by Cardiac Magnetic Resonance (cMRI)
2. Change in cardiac muscle function and structure by assessment of left ventricular end-systolic volume [ Time Frame: At Month 12 ]
   Mean change from baseline in left ventricular end-systolic volume as assessed by Cardiac Magnetic Resonance (cMRI)
3. Change in cardiac muscle function and structure by assessment of left ventricular end-diastolic volume [ Time Frame: At Month 12 ]
   Mean change from baseline in left ventricular end-diastolic volume as assessed by Cardiac Magnetic Resonance (cMRI)
4. Change in elbow and distal level upper limb function [ Time Frame: At Month 12 ]
   Mean change from baseline in mid [elbow] plus distal level upper limb function in Performance of the Upper Limb test, version 2 (PUL 2.0); items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation
5. Change in hand-to-mouth function in the context of functional eating [ Time Frame: At Month 12 ]
   Mean change from baseline in the functional ability of eating 10 bites evaluated by Duchenne Video Assessment (DVA) using a video record of patient performing the task at home. Physical therapists score the patient's quality of movement in the video using scorecards with pre-specified compensatory movement criteria.
6. Change in hand-to-mouth function [ Time Frame: At Month 12 ]
   Mean change from baseline in item 7 [hand-to-mouth] in Performance of the Upper Limb test, version 2 (PUL 2.0); items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation
7. Number of patients with total loss of hand-to-mouth function [ Time Frame: At Month 12 ]
   Proportion of patients with total loss of hand-to-mouth function as assessed by item 7 [hand-to-mouth] in Performance of the Upper Limb test, version 2 (PUL 2.0)
8. Changes in patient-reported upper limb function [ Time Frame: At Month 12 ]
   Mean change from baseline in Duchenne Muscular Dystrophy Upper Limb Patient-Reported Outcome Measures (DMD UL PROM) questionnaire. Patient or caretaker evaluates the perceived difficulty in performing activities of daily living on a 3-level scale: 0=impossible without help, 1=can do task with difficulty, 2= can do task easily.
9. Changes in cardiac inflammation biomarker, creatine kinase MB isoenzyme [CK-MB] [ Time Frame: At months 1, 3, 6, 9, 12 ]
   Mean change from baseline in CK-MB blood levels - MB fraction (% of total CK).
10. Evaluation of disease modifying effects of CAP-1002 [ Time Frame: At Month 24 ]
    Mean change from baseline between patients initially randomized to either CAP-1002 or placebo in full Performance of the Upper Limb test, version 2 (PUL 2.0) at Month 24 in the open label phase of the trial. items in PUL 2.0 are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Male subjects at least 10 years of age at time of consent who are willing and able to provide informed consent to participate in the trial and diagnosed with DMD as confirmed by the Investigator
2. Genetically confirmed DMD
3. Performance of the Upper Limb test (PUL) entry item scores 2-6 and total PUL score less than or equal to 40
4. Reduced ability to walk/run (if ambulatory): subjects must take more than 10 seconds for the 10-meter walk/run (i.e., velocity < 1 meter/second)
5. If non-ambulatory, loss of independent ambulation between 10th and 18th year birthday
6. 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
7. Current and up-to-date immunizations
8. Adequate venous access for parenteral IP infusions and routine blood collection
9. Assessed by the Investigator as willing and able to comply with the requirements of the trial
10. Sexually active subjects and their partners who are fertile must agree to use effective method(s) of contraception

Exclusion Criteria:

1. Left ventricular ejection fraction (LVEF) less than or equal to 35% prior to randomization
2. Elbow-flexion contractures > 30° in both extremities
3. Body mass index (BMI) > 45
4. Percent predicted forced vital capacity (FVC%) < 35% within 6 months prior to randomization
5. Inability to perform consistent PUL 2.0 measurement within ± 2 points without shoulder domain or within ± 3 points with shoulder domain during paired testing at screening
6. Risk of near-term respiratory decompensation in the judgment of the Investigator, or the need for initiation of day and night non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L at screening
7. History of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis
8. Acute respiratory illness within 30 days prior to screening and during screening
9. Initiation of nocturnal non-invasive ventilation within 30 days prior to screening
10. Planned or anticipated thoracic or spinal surgery within the 6 months following randomization
11. Planned or anticipated lower extremity surgery within the 6 months following randomization, if ambulatory
12. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products
13. Initiation of treatment with metformin or insulin within 3 months prior to randomization
14. Initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD and/or non-weight based adjustments within 12 months prior to randomization
15. Treatment with human growth hormone within 3 months prior to randomization, unless on a stable dose allowing for weight-based dose adjustments (as determined by the site Investigator) for at least 24 months prior to randomization
16. Treatment with a cell therapy product within 12 months prior to randomization; any prior exposure to CAP-1002 will be excluded
17. Treatment with an investigational product within 6 months prior to randomization
18. History, or current use, of drugs or alcohol that could impair the ability to comply with participation in the trial
19. Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator
20. Inability to undergo a cardiac MRI

Contacts and Locations

Contacts

Contact: Sophie Guillaume; 858-727-1755; clinicaltrialsgov@capricor.com

Locations

United States, Arkansas

Arkansas Children's Hospital; Recruiting

Little Rock, Arkansas, United States, 72202

Contact: Ankita Patel 501-364-1035 patelA1@archildrens.org

Principal Investigator: Aravindhan Veerapandiyan, MD

United States, California

University of California, Davis; Recruiting

Sacramento, California, United States, 95817

Contact: David Rodriguez 916-734-0897 davrodri@ucdavis.edu

Principal Investigator: Craig McDonald, MD

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Amelia Decker 720-777-5990 amelia.decker@childrenscolorado.org

Principal Investigator: Susan Apkon, MD

United States, Georgia

Rare Disease Research, LLC; Recruiting

Atlanta, Georgia, United States, 30329

Contact: Brenda Almaras 678-883-6897 brenda.almaras@rarediseaseresearch.com

Principal Investigator: Han Phan, MD

United States, Iowa

University of Iowa Hospitals and Clinics; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Elizabeth Gaffney 319-384-9618 Elizabeth-Gaffney@uiowa.edu

Principal Investigator: Katherine Mathews, MD

United States, Massachusetts

Boston Children's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Abigail Druffner 857-218-4677 abigail.druffner@childrens.harvard.edu

Principal Investigator: Partha Ghosh, MD

United States, Missouri

Saint Louis Children's Hospital; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Michelle Brown 314-362-1146 brownmichelle@wustl.edu

Principal Investigator: Arun Varadhachary, MD

United States, Ohio

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

Contact: Angela Edmondson 513-636-9285 Angela.edmondson@cchmc.org

Principal Investigator: Cuixia Tian, MD

United States, Utah

University of Utah Hospital; Recruiting

Salt Lake City, Utah, United States, 84112

Contact: Sarah Moldt 801-585-9399 sarah.moldt@hsc.utah.edu

Principal Investigator: Russell Butterfield, MD

United States, Wisconsin

Children's Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Rebecca Rehborg 414-266-3355 rrehborg@mcw.edu

Principal Investigator: Matthew Harmelink, MD

Sponsors and Collaborators

Capricor Inc.

Investigators

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

More Information

• Responsible Party: Capricor Inc.
• ClinicalTrials.gov Identifier: NCT05126758
• Other Study ID Numbers: CAP-1002-DMD-04
• First Posted: November 19, 2021
• Last Update Posted: January 11, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Capricor Inc.:

Duchenne Muscular Dystrophy; Cell Therapy; Performance of the Upper Limb; Ambulatory; Non-Ambulatory

Additional relevant MeSH terms:

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