Capricor Therapeutics Testing DMD Cell Therapy Deramiocel’s Mettle in Phase 3 HOPE-3 Clinical Trial

Capricor Therapeutics is currently evaluating deramiocel (also known as CAP-1002), an investigational allogeneic cardiosphere-derived cell therapy intended for the treatment of Duchenne muscular dystrophy (DMD) cardiomyopathy, in the phase 3 HOPE-3 clinical trial (NCT05126758).¹ In honor of Duchenne Action Month, observed annually in September by the patient and clinician communities, and following up on World Duchenne Day, held every year on September 7, CGTLive® is taking a closer look at this ongoing study.

HOPE-3, which was launched on June 22, 2022, has an estimated primary completion date of December 2025 and an estimated completion date of December, 2027. According to the clinicaltrials.gov page, which was most recently updated on June 13, 2025, the study is active and has enrolled 104 patients in total, but is no longer recruiting new patients. The trial is taking place at sites in Arizona, Arkansas, California, Colorado, Georgia, Illinois, Iowa, Massachusetts, Missouri, North Carolina, Ohio, Texas, Utah, Virginia, Washington, and Wisconsin. Craig McDonald, MD, the chair of the Department of Physical Medicine & Rehabilitation at University of California, Davis, is serving at HOPE-3's principal investigator and Mark Awadalla, BS, the chief development officer at Capricor, is serving as the study director.

HOPE-3 takes the form of a double-blind, placebo-controlled study, in which participants are randomly assigned to receive either deramiocel or a placebo in a 1:1 ratio. Furthermore, participants were recruited into 1 of 2 cohorts. In cohort A, which was estimated to enroll approximately 58 participants, patients in the treatment group were treated with deramiocel product manufactured at a facility in Lose Angeles, CA (CAP-1002A). On the other hand, in cohort B, estimated to enroll 44 participants, patients in the treatment group were treated with deramiocel product manufactured at a facility in San Diego, CA (CAP-1002B). Patients are to receive doses of either deramiocel or the placebo on day 1 of the study, and then 3 months, 6 months, and 9 months. Via an open-label portion of the study, all participants may receive doses of deramiocel at 12 months, 15 months, 18 months, and 21 months. An additional long term open-label extension portion will allow patients to continue receiving doses of deramiocel every 3 months until deramiocel is approved by the FDA or a decision is made to end the trial.

The primary end point of HOPE-3 is the mean change from baseline in the Performance of the Upper Limb test, version 2 (PUL 2.0) Total Score at 12 months posttreatment. The study’s many secondary end points include the mean changes from baseline in left ventricular ejection fraction (LVEF) as assessed by Cardiac Magnetic Resonance (cMRI), in left ventricular end-systolic volume as assessed by cMRI, in left ventricular end-diastolic volume as assessed by cMRI, in mid [elbow] plus distal level upper limb function in PUL 2.0, in aTotal Global Statistical Test combining PUL 2.0 score, LVEF assessment by cMRI, and the Patient Global Impression of Severity (PGI-S), in creatine kinase MB isoenzyme blood levels – MB fraction, in functional ability to eat 10 bites as assessed by Duchenne Video Assessment, and in item 7 on PUL 2.0. Additional secondary end points include the proportion of patients who have a total loss of hand-to-mouth function according to PUL 2.0 item 7 and the mean change from baseline on the Duchenne Muscular Dystrophy Upper Limb Patient-Reported Outcome Measures questionnaire. All secondary end points will be assessed at 12 months after the initial treatment.

HOPE-3 is open to men and boys aged 10 years or older with a diagnosis of DMD based on clinical and phenotypic manifestations and confirmatory genetic testing. Eligible participants must have PUL entry item scores 2 to 6 and a total PUL score of 40 or less. For cohort A, enrollment of patients with PUL entry score 6 who are exon 44 skipping–amenable or who carry deletions spanning exons 3 through 7 will be limited to 10% or less of the overall study population, or roughly 6 patients. Ambulatory participants must demonstrate reduced walking or running ability, defined as requiring more than 10 seconds to complete the 10-meter walk/run. Nonambulatory participants are eligible if they lost independent ambulation between turning 10 and 18 years of age; those who are nonambulatory between ages 9 and 10 years may be considered with prior sponsor approval.

All patients must be receiving standard-of-care therapy at a multidisciplinary DMD center, with regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and home-based range of motion exercises. Systemic glucocorticoid therapy must have been maintained for at least 12 months prior to enrollment, with a stable dose for at least 6 months, except for weight-based dose adjustments or reductions of 10% or less because of toxicity. Patients on chronic deflazacort are eligible if they received an equivalent prednisone or prednisolone bridge for 30 days or less in the 6 months prior to being randomly assigned to a treatment group in the study. Up-to-date immunizations, according to the Centers for Disease Control and Prevention pediatric and adolescent immunization schedule, are required at the discretion of the investigator. Participants must also have adequate venous access to permit parenteral infusions and routine blood draws. Sexually active participants and their partners who are fertile must agree to use effective contraception for the duration of the trial.

Patients will be excluded if they have an LVEF of 35% or less prior to being randomly assigned, elbow flexion contractures of more than 30° in both arms, or a BMI greater than 45. Additional exclusions include a predicted forced vital capacity (FVC%) of less than 35% within 6 months of being randomly assigned; the inability to perform consistent PUL 2.0 testing within ±2 points without shoulder domain or ±3 points with shoulder domain at in paired testing carried out at screening; a risk of near-term respiratory decompensation in the view of the investigator; or the need for day and night noninvasive ventilator support. Patients with chronic respiratory disease unrelated to DMD that requires continuous or intermittent management, such as asthma, bronchitis, or tuberculosis, will not be eligible, nor will those with acute respiratory illness within 30 days of screening or those who began nocturnal noninvasive ventilation within 30 days of screening. Planned or anticipated thoracic or spinal surgery within 6 months after random assignment, or planned or anticipated lower extremity surgery in ambulatory patients during the same period, will also be exclusionary.

Additional exclusion criteria include hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products; initiation of metformin or insulin within 3 months prior to random assignment; initiation of FDA-approved exon skipping therapies for DMD within 12 months prior to random assignment (or nonweight-based adjustments during the same timeframe); or treatment with human growth hormone within 3 months before random assignment, unless on a stable regimen for at least 24 months that in the investigator’s opinion allows for weight-based adjustments. Patients previously treated with any cell therapy within 12 months, and those who have any prior exposure to deramiocel, will be ineligible, as will those who received any investigational product within 6 months prior to random assignment. A history of use of drugs or alcohol that may impair trial participation, or the general inability to comply with the investigational plan and follow-up visits for any reason, are also exclusionary. Patients unable to undergo cardiac MRI will not be eligible, although those in cohort B with hypersensitivity to gadolinium or who are unable to tolerate it because of renal insufficiency may forgo the late gadolinium enhancement (LGE) assessment but must still complete a noncontrast cardiac MRI. Finally, patients in cohort B with PUL entry score 6, those who are exon 44 skipping–amenable, and those who carry exon 3 through 7 deletions are not eligible.

Deramiocel is comprised of about 150 million cardiosphere-derived cells (CDCs). Notably, Capricor submitted a biologics license application (BLA) to the FDA earlier this year, but received a complete response letter (CRL) from the agency in July 2025.² The BLA, however, was based on results of the completed HOPE-2 clinical trial (NCT03406780) and HOPE-2’s ongoing open-label extension (OLE) study (HOPE-2-OLE; NCT04428476), with data from these studies being compared to an FDA funded natural history dataset; data from HOPE-3 was not included.

“We are surprised by this decision by the FDA,” Linda Marbán, PhD, the chief executive officer of Capricor, said in a July 2025 statement.² “We have followed their guidance throughout the process. Prior to the CRL, the review had advanced without major issues, including a successful prelicensure inspection and completion of the mid-cycle review. Capricor plans to submit data from the phase 3 HOPE-3 clinical trial to provide additional evidence of effectiveness from an adequate and well-controlled study. The HOPE-3 trial is a randomized, double-blind, placebo-controlled clinical trial of 104 patients, with topline results expected in the third quarter of 2025. We believe these data, if positive, along with our existing long-term clinical results showing cardiac stabilization, preservation of skeletal muscle function, and a consistent safety profile, could support efforts to resolve the questions raised by the FDA for the treatment of cardiomyopathy associated with DMD. While this was an unexpected decision by the FDA, we remain committed to the DMD community to get deramiocel through the approval process.”

More recently, in September 2025, Capricor published its full response to the FDA’s CRL after the agency published the full CRL on its website.³ According to the company, the response to the CRL provides clarifications on the feedback received and insight on its proposed plans to address remaining issues.

“Transparency is vital in regulatory communications, especially when patients are waiting for therapies with the potential to alter the course of devastating diseases such as Duchenne muscular dystrophy,” Marbán said in a statement at the time.³ “Our focus remains on working closely with the FDA to resolve the outstanding issues and to advance deramiocel toward approval. While we respect the FDA’s process, we believe it is important that the public has visibility into both the CRL and our detailed written response submitted to the agency. We are now awaiting the official minutes from our recent Type A meeting with the FDA review team, expected to be issued later this quarter, which will help define the next steps in our regulatory pathway. Looking ahead, we expect top-line HOPE-3 data in the fourth quarter of 2025, and our discussions with the FDA have centered on how these data will inform and support the timing of our BLA resubmission.”

REFERENCES
1. ClinicalTrials.gov. Website. Accessed September 22, 2025. https://clinicaltrials.gov/study/NCT05126758?term=NCT05126758&rank=1
2. Capricor Therapeutics provides regulatory update on Deramiocel BLA for Duchenne muscular dystrophy. News release. Capricor Therapeutics. July 11, 2025. Accessed September 22, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/319/capricor-therapeutics-provides-regulatory-update-on
3. Capricor Therapeutics responds to FDA posting of complete response letter (CRL) for deramiocel. News release. Capricor Therapeutics. September 9, 2025. Accessed September 22, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/325/capricor-therapeutics-responds-to-fda-posting-of-complete