The study evaluating 68 boys and young men with Duchenne muscular dystrophy will consist of therapy with off-the-shelf cardiosphere-derived cells.
CAP-1002, AN ALLOGENEIC off-the-shelf cell therapy developed by Capricor Therapeutics, will be evaluated as a treatment for patients with Duchenne muscular dystrophy (DMD) in an upcoming pivotal phase 3 trial, HOPE-3 (NCT05126758), a multicenter, randomized, double-blind, placebo-controlled study that will include both nonambulatory and ambulatory boys and young men who meet eligibility criteria (TABLE).1
The therapy consists of allogeneic, off-the-shelf cardiosphere-derived cells (CDCs), which have been the subject of more than 100 peer-reviewed scientific publications since they were discovered in 2007. In CAP-1002, the cells release exosomes that are taken up largely by macrophages and T cells and begin a cycle of repair. CAP-1002 has been granted orphan drug designation by the FDA.2
HOPE-3 is expected to be complete in late June 2024. An estimated 68 participants will be randomly assigned to receive CAP-1002 at a dose of 150 million CDCs or placebo every 3 months for a total of 4 doses over a 12-month period. Led by Craig M. McDonald, MD, professor and chair of the Department of Physical Medicine and Rehabilitation at University of California, Davis, the study will use mean change in full upper limb function at month 12 as measured by Performance of the Upper Limb (PUL) version 2.0 scores as the primary end point. The secondary outcome will be cardiac muscle function and structure as measured by change from baseline in ejection fraction.
The study will include only males at least 10 years or older at time of consent who have genetically confirmed DMD. Participants are expected to have reduced ability to walk/run, have up-to-date immunizations, and have received treatment with systemic glucocorticoids for at least 12 months and at a stable dose for at least 6 months prior to study participation. The trial will include visits at screening, baseline/day 1, and months 3, 6, and 9. Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead electrocardiogram, and clinical laboratory testing.2
In September 2021, the company announced positive data from its phase 2 HOPE-2 study (NCT03406780), which showed that CAP-1002 met its primary end point on decline in mid–PUL version 1.2. Patients showed a slowing of this outcome by 71% (P = .01) compared with placebo. Additionally, the trial also met additional end points, with significant differences seen on the full PUL version 2.0 (P = .04) and cardiac end point of ejection fraction (P = .02) compared with placebo.3
HOPE-2, conducted across 9 sites in the US, enrolled 20 participants (12 placebo and 8 treated) with DMD. In total, 80% of the patients were nonambulatory, with other demographic and baseline characteristics similar between the 2 groups. Besides 2 hypersensitivity reactions seen early in the trial—which were mitigated with a common premedication regimen—CAP-1002 was well tolerated with no serious safety signals.
“This groundbreaking study is extremely exciting as we saw statistically significant changes of CAP-1002 in both skeletal and cardiac function. For these older [patients] who have limited therapeutic options, these data support the belief that CAP-1002 may become an important therapeutic option and possibly slow the progression of DMD,” McDonald said in a statement following the announcement of the results.3
CAP-1002 also was previously evaluated in the HOPE-Duchenne phase 1/2 trial (NCT02485938) for DMD-associated cardiomyopathy, which enrolled 25 participants across 3 sites in the US. All participants had significant cardiac scarring and approximately two-thirds were dependent on wheelchairs at the time they began the trial. During the 12-month course of the trial, CAP-1002 demonstrated a safe and well-tolerated profile, along with significant and sustained signals of improvement in cardiac and skeletal muscle function in patients with DMD.4
In January 2022, Capricor Therapeutics announced that it had entered a partnership with Nippon Shinyaku Co (NS Pharma) for the exclusive commercialization and distribution of the therapy in the US. Linda Marbán, PhD, CEO of Capricor, said in a news release that the partnership “aligns us with a larger, seasoned pharmaceutical company experienced in rare disease with specific expertise in DMD.” She cited NS Pharma’s 2020 approval and launch of viltolarsen (Viltepso) for patients with DMD amenable to exon 53 skipping, which at the time was only the second FDA-approved therapy for this specific DMD gene mutation.5