Open-label Extension of the HOPE-2 Trial (HOPE-2-OLE)

Open-Label Extension of the HOPE-2 Duchenne Muscular Dystrophy Trial

This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will explore the safety and efficacy of sixteen intravenous administrations of CAP-1002, each separated by three months. Subjects will undergo a targeted screening during a 30-day screening period, eligible subjects will then undergo baseline safety and efficacy assessments on Day 1 prior to their first infusion of CAP-1002.

Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45 and 48. Safety and efficacy assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45 trial visits, unless otherwise indicated.

All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. Subjects will be observed in the outpatient setting for at least two hours post infusion and then discharged the same day, if medically cleared by the site Investigator.

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Biological: CAP-1002

Detailed Description

This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will explore the safety and efficacy of sixteen intravenous administrations of CAP-1002, each separated by three months. Subjects will undergo a targeted screening during a 30-day screening period to determine eligibility based on protocol inclusion and exclusion criteria.

Eligible subjects will undergo baseline safety and efficacy assessments on Day 1 prior to their first infusion of CAP-1002. Administration of CAP-1002 (Day 1) should occur within a maximum of 30 days following confirmation of eligibility.

Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12 (± 14 days, each), 15, 18, 21, 24, 27, 30, 30, 33, 36, 39, 42, 45 and 48 (± 21 days, each). Safety and efficacy assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45 trial visits, unless otherwise indicated.

All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. Prior to each CAP-1002 administration, medications will be administered to the subject as determined by the Investigator based on the pre-treatment guidelines as outlined in the protocol and/or institutional protocols to minimize the risk of potential severe allergic reactions such as anaphylaxis. Subjects will be observed in the outpatient setting for at least two hours post infusion and then discharged the same day if medically cleared by the site Investigator. If clinically indicated, an unscheduled in-person visit will be performed at the investigative site with targeted assessments based on presentation of signs and symptoms following any infusion.

• Study Type: Interventional
• Enrollment (Actual): 13
• 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
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • 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

Description

Inclusion Criteria:

1. Documented enrollment in the HOPE-2 trial and completion of trial follow-up through Month 12
2. 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
3. Adequate venous access for intravenous CAP-1002 infusions in the judgement of the Investigator
4. Assessed by the Investigator as willing and able to comply with the requirements of the trial

Exclusion Criteria:

1. Planned or likely major surgery in the next 12 months after planned first infusion
2. 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
3. History of non DMD-related chronic respiratory disease including, but not limited to, asthma, bronchitis, and tuberculosis
4. Acute respiratory illness within 60 days prior to first infusion
5. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products
6. Treatment with an investigational product ≤ 6 months prior to first infusion
7. History, or current use, of drugs or alcohol that could impair ability to comply with participation in the trial
8. Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open-label arm; Open-label CAP-1002 will be administered to all subjects enrolled in the trial	Biological: CAP-1002; Peripheral infusion of 150 million allogeneic cardiosphere-derived cells administered every three months; Other Names: Allogeneic Cardiosphere-Derived Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary safety endpoint is the incidence and severity of all treatment-emergent adverse events	Change from baseline in the incidence and severity of all treatment-emergent adverse events	At Month 12 timepoint
The primary efficacy endpoint is change in upper limb function	Mean change from baseline in upper limb function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) Total Score. 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.	At Month 12 timepoint

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of all treatment-emergent adverse events	Change from baseline in the incidence and severity of all treatment-emergent adverse events	At Month 24, Month 36, and Month 48 timepoint
Change from baseline in upper limb function	Mean change from baseline in upper limb function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) Total Score. 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.	At Month 24, Month 36, and Month 48 timepoint
Change from from baseline in distal-level (wrist and hand) upper limb function	Mean change from baseline in distal-level (wrist and hand) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 2 and 3. 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.	At Month 12, Month 24, Month 36, and Month 48 timepoint
Change from from baseline in mid-level (elbow) upper limb function	Mean change from baseline in mid-level (elbow) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 4 and 5. 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.	At Month 12, Month 24, Month 36, and Month 48 timepoint
Change in cardiac muscle function and structure by assessment of Left Ventricular Ejection Fraction (LVEF)	Mean change from baseline in LVEF as assessed by Cardiac Magnetic Resonance (cMRI)	At Month 24, Month 36, and Month 48 timepoint

Collaborators and Investigators

• Sponsor: Capricor Inc.
• Investigators: Study Director: Mark Awadalla, Capricor Inc.; Principal Investigator: Craig McDonald, MD, UC Davis

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Actual): February 16, 2022
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: DMD, Muscular dystrophy, Duchenne
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: CAP-1002-DMD-02-OLE

Drug and device information, study documents

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