A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

NCT03406780 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CAP-1002-DMD-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 9

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12

  Change from baseline in functional capacity as assessed by the mid-level (elbow) dimension of PUL version 1.2 at Month 12 expressed as percentile ranked change. PUL 1.2 scale assesses motor performance in the upper limb. PUL 1.2 included 22 items. One entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (score 0 to 16); Elbow Level (score 0 to 34); Distal Level Dimension (score 0 to 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).

  Baseline, Month 12

• Number of Participants Experiencing Acute Respiratory Decompensation

  Acute respiratory decompensation was defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation.

  Baseline through Month 12

• Number of Participants With Hypersensitivity Reactions

  Hypersensitivity reaction was defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset less than or equal to (\<=) 2 hours post-infusion and lasting less than (\<) 24 hours, in the absence of clinical signs of concomitant infection.

  Baseline through Month 12

• Number of Participants With All-cause Mortality

  Number of participants who died due to any cause were reported.

  Baseline through Month 12

• Number of Participants With Serious Adverse Events (SAEs)

  A SAE was defined as an AE that results in any of the following outcomes: Death; life-threatening adverse event; Inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.

  Baseline through Month 12

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure

  TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. The Investigator assessed the relationship (causality) of an AE to the investigational product and administration procedure.

  Baseline through Month 12

• Number of Participants With Immune Sensitization Syndrome

  Immune sensitization syndrome is defined as a) clinical signs and symptoms that are consistent with systemic inflammation (e.g.,fever, leukocytosis, rash, arthralgia), with an onset \>=24 hours after infusion of the investigational product, in the absence of clinical signs of concomitant infection, and b) an elevation of anti-Human Leukocyte Antigen (anti-HLA) antibodies against the Donor-Specific Antibody (DSA) cells, which is detected \<=30 days after the onset of syndrome, that meets the following criteria: i) 2000 mean fluorescence intensity if mean fluorescence intensity is \<=1000 at baseline, or ii) \>=2 times the baseline value.

  Baseline through Month 12

Secondary Outcomes (3)

• Number of Participants With TEAEs and Severity of TEAEs

  Baseline through Month 12

• Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9

  Baseline, Months 3, 6, and 9

• Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12

  Baseline, Months 6 and 12

Other Outcomes (5)

• Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12

  Month 6 and 12

• Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12

  Month 6 and 12

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

  Month 6 and 12

Study Arms (2)

CAP-1002

EXPERIMENTAL

Patients will receive 150 million Cardiosphere-derived Cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses.

Biological: CAP-1002

Placebo

PLACEBO COMPARATOR

Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses.

Drug: Placebo

Interventions

CAP-1002 BIOLOGICAL

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, anti-inflammatory, and pro-angiogenic.

Also known as: Cardiosphere-Derived Cells, CDCs, deramiocel

CAP-1002

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants at least 10 years of age at time of consent
• Participants willing and able to provide informed consent to participate in the trial if \>= 18 years of age, and assent with parental or guardian informed consent if \< 18 years of age
• Participants with diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf pseudohypertrophy, Gowers' sign, and gait impairment before 7 years of age) with confirmatory genetic testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
• Participants with performance of the Upper Limb entry item score 2-5
• Participants if ambulatory, 10-meter walk/run velocity \< 1 meter/second
• Participants with loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at most, several steps independently is not considered ambulation)
• Participants who receiving standard of care therapy at an experienced, multidisciplinary, DMD center as evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and at-home range of motion exercises
• Participants who received treatment with a systemic glucocorticoid is required for at least 12 months prior to randomization. The dose must remain stable for at least 6 months prior to randomization with the exception of either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for toxicity. For patients on chronic deflazacort, treatment with an equivalent dose of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 6 months prior to randomization is acceptable
• Participants with current and up-to-date immunizations according to children and adolescent Centers for Disease Control immunization schedule, unless contraindicated, including the following: meningococcal and meningococcal B; tetanus, diphtheria \& acellular pertussis (Tdap); and pneumococcal polysaccharide vaccinations
• Participants with adequate venous access for parenteral IP infusions and routine blood collections in the judgement of the Investigator
• Participants assessed by the Investigator as willing and able to comply with the requirements of the trial

You may not qualify if:

• Participants with Left Ventricular Ejection Fraction (LVEF) \< 35%
• Participants with elbow-flexion contractures \> 30° in both extremities
• Participants with Body Mass Index (BMI) \> 45
• Participants with documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene
• Participants with documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7
• Participants with percent predicted FVC (FVC%p) \< 35%
• Participants with inability to perform consistent FVC measurement within ±15% during paired testing at screening
• Participants with risk of near-term respiratory decompensation in the judgment of the investigator, or the need for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L at screening
• Participants with history of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis
• Participants with acute respiratory illness within 30 days prior to screening
• Participants with initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated need to initiate non-invasive ventilation within the 12 months following screening
• Participants with planned or anticipated thoracic or spinal surgery within the 12 months following randomization
• Participants with planned or anticipated lower extremity surgery within the 12 months following randomization, if ambulatory
• Participants with known hypersensitivity to Dimethyl Sulfoxide (DMSO) or bovine products
• Participants with initiation of treatment with metformin or insulin within 3 months prior to randomization

Sponsors & Collaborators

• Capricor Inc.: lead

Study Sites (9)

University of California, Davis

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Children's Hospital Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 35279258 RESULT

Related Links

• Company website

MeSH Terms

Conditions

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

Interventions

chenodeoxycholate sulfate conjugate

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Mark Awadalla
• Organization: Capricor, Inc.

clinicaltrialsgov@capricor.com

858-727-1755

Study Officials

• Craig McDonald, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: January 23, 2018
• Study Start: April 4, 2018
• Primary Completion: March 10, 2020
• Study Completion: March 10, 2020
• Last Updated: May 28, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)