rAAVrh74.MHCK7.DYSF.DV for Treatment of Dysferlinopathies

• Status: Completed
• Trial end date: 2019-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The proposed clinical trial is a double-blind, randomized controlled study with direct intramuscular injection of rAAVrh.74.MHCK7.DYSF.DV gene vector to the extensor digitorum brevis muscle (EDB). Two cohorts of subjects with dysferlin deficiency, each with proven mutations will undergo gene transfer. A minimum of three subjects will be enrolled into each cohort.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nationwide Children's Hospital; Sarepta Therapeutics, Inc.

Criteria

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