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This Phase 1 study is a double-blind, randomized controlled trial of direct intramuscular injection of the rAAVrh74.MHCK7.DYSF.DV gene vector into the extensor digitorum brevis muscle in people with dysferlin deficiency. Two cohorts of subjects with proven mutations undergo gene transfer, with a minimum of three subjects per cohort. Eligibility requires being aged 18 or older, being non-ambulant (unable to walk 10 meters in 30 seconds or less), established mutations on both alleles of the dysferlin gene, and sufficient muscle preservation on magnetic resonance imaging.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria: * Must be Non-ambulant (cannot walk 10 meters in ≤ 30 sec) and age 18 years or older * Established mutations of the dysferlin gene on both alleles * Impaired muscle function but with sufficient muscle preservation to ensure muscle transfection based on magnetic resonance image of the EDB showing sufficient muscle preservation to permit transfection * Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate), during the first six months after gene transfer (females) or until two negative sperm samples are obtained post gene transfer (males). Exclusion Criteria: * Active viral infection based on clinical observations or serological evidence of HIV, or Hepatitis A, B or C infection * The presence of a Dysferlin mutations without weakness or loss of function * Symptoms or signs of cardiomyopathy, including: * Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs * Echocardiogram with ejection fraction below 40% * Diagnosis of (or ongoing treatment for) an autoimmune disease * Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥ 20.0 K/µL) or an absolute neutrophil count \< 1.5K/µL * Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer * Pregnancy * AAVrh74 or AAV8 binding antibody titers \> 1:50 as determined by ELISA immunoassay * Abnormal laboratory values in the clinically significant range in the table below, based upon normal values in the Nationwide Children's Hospital Laboratory: GGT, Total Bilirubin, Cystatine, Hemoglobin, White Blood Cells