Solid Biosciences’ INSPIRE DUCHENNE Study Puts DMD Gene Therapy SGT-003 to the Test
CGTLive® took a closer look at the first-in-human clinical trial for the next-generation gene therapy.
Solid Biosciences SGT-003, an investigational next-generation adeno-associated virus (AAV) vector-based gene therapy for Duchenne muscular dystrophy (DMD), is currently being evaluated in the phase 1/2 INSPIRE DUCHENNE clinical trial (NCT06138639).1
Notably, SGT-003 uses the company’s proprietary AAV-SLB101 capsid to deliver h-µD5, a transgene encoding for a microdystrophin protein containing the R16 and R17 nNos binding protein domains. The first-in-human INSPIRE DUCHENNE study, which takes the form of an open-label, nonrandomized trial, was initiated on May 6, 2024. INSPIRE DUCHENNE is expected to enroll an estimated 43 patients aged 4 to 11 years. Participants will be assigned to 1 of 2 cohorts, with cohort 1 including patients aged less than 7 years and cohort 2 including patients aged 7 years and older. Patients in both cohorts will receive a single dose of SGT-003, at 1x1014 vg/kg, via intravenous infusion.
According to the clinicaltrials.gov page, which was most recently updated on January 17, 2025, INSPIRE DUCHENNE is currently recruiting patients at locations in Little Rock, AK, Los Angeles, CA, Sacramento, CA, Columbus, OH, Norfolk, VA, and Toronto, Canada. The study has an estimated primary completion date of May 6, 2027 and an estimated completion date of May 6, 2031. The investigational new drug (IND) application enabling the launch of the trial in the United States was cleared by the FDA in November 2023.
“We are pleased to have the FDA’s clearance to proceed into the clinic with SGT-003, a new, innovative gene therapy candidate for Duchenne,” Bo Cumbo, BS, the president and chief executive officer of Solid Biosciences, said in a statement at the time of the IND clearance.1 “SGT-003 combines our differentiated microdystrophin transgene with a next generation muscle-tropic capsid and a transient transfection manufacturing process that may help address the unmet needs for the Duchenne community.”
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The study’s primary end point is the incidence of treatment-emergent adverse events in the 360 days posttreatment. The study’s secondary end points include the change from baseline in microdystrophin protein levels at 90 and 360 days posttreatment; the change from baseline in North Star Ambulatory Assessment (NSAA) total score at 540 days posttreatment; and the change from baseline in stride velocity 95th centile, which will be evaluated with a wearable activity monitoring device, at 540 days posttreatment.
The study is open to boys in the aforementioned age range who have a clinical diagnosis of DMD and a documented dystrophin gene mutation predictive of the DMD phenotype, as confirmed by genetic testing. Participants must be able to walk without the use of an assistive device, test negative for AAV antibodies, and be on a stable regimen of oral daily prednisone (0.5 mg/kg/day or greater) or deflazacort (0.75 mg/kg/day or greater) for at least 12 weeks before enrollment. In addition, patients are required to have a body weight of 50 kg or less and to meet criteria for 10-meter walk/run time and time to rise from supine.
Patients who were treated with dystrophin modifying drugs in the 3 months before screening will not be eligible to participate. In addition, patients who have any history of treatment with any gene transfer drug will be excluded from participation, as will patients who have been exposed to certain other approved and investigational drugs in the 3 months prior to screening or in 5 half-lives since their last dose of such a drug (based on which of these is longer). Furthermore, patients who have a DMD diagnosis associated with a deletion mutation in exons 1 through 11 or exons 42 through 45 in the DMD gene will be ineligible for the trial.
Solid Biosciences announced early findings from INSPIRE DUCHENNE in November 2024.2 At the time, 3 patients had been dosed and no serious adverse events had been reported.
“We are highly encouraged by the progress we have made with the INSPIRE DUCHENNE clinical trial over the past quarter, including the activation of University of California, Davis as a clinical site in October,” Cumbo said in a November 2024 statement.2 “SGT-003 continues to be well tolerated in the first 3 patients dosed. As a result of encouraging early results observed in these patients, we have implemented an updated study protocol amending the clinical trial across key parameters, including enrollment size, age range, and clinical end point timelines. With these changes, along with other planned studies, we believe our clinical development program provides significant flexibility in pursuing potential regulatory pathways, with the goal of accelerating a new treatment option to this underserved patient community. We are currently enrolling patients under the expanded INSPIRE DUCHENNE protocol and will continue dosing throughout the rest of 2024 and into 2025.”
Notably, a month prior to the IND clearance for INSPIRE DUCHENNE, in October 2023, Solid announced that it was deprioritizing its earlier-generation lead candidate gene therapy SGT-001, which was also being developed for the treatment of DMD, in favor of advancing SGT-003.3 SGT-001, which utilizes an AAV9 vector that contains a muscle-specific promoter and microdystrophin, is being evaluated in the phase 1/2 IGNITE-DMD clinical trial (NCT03368742). Although IGNITE-DMD passed its primary completion date on October 17, 2022, and is no longer recruiting new patients, it remains active for tracking long-term data on the patients who were treated in the study. It has an estimated completion date of October 15, 2026.
