Gene Transfer Clinical Trial for LGMD2D (Alpha-sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA

• Status: Completed
• Trial end date: 2019-03-14
• Target enrollment: 0
• Participant gender: All

Summary

Dose escalation study of self-complementary (sc) AAVrh74.tMCK.hSGCA delivered to single leg (low dose n=2) and bilaterally (n=6) via a major lower limb artery to the whole lower limb of limb girdle muscular dystrophy type 2D (LGMD2D; alpha-sarcoglycan deficient) patients.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jerry R. Mendell

Criteria

Inclusion Criteria

• Subjects age 7 or older; cohort 1A must be adult and wheelchair-dependent

• Proven alpha-sarcoglycan deficiency by muscle biopsy or DNA testing.

• Onset of weakness by 5 years age based on history of difficulty running, jumping and climbing stairs.

• Subject enrolled in Cohort 1A must be adult and wheelchair dependent

• Subjects enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (i.e. a Gowers' sign, use a handrail for climbing stairs) and walk ≤ 80% of predicted distance on the 6MWT based on normative data.

• Males and females of any ethnic group will be eligible

• Ability to cooperate with muscle testing.

• Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate), during the first six months after gene therapy (females) or until two negative sperm samples are obtained post gene transfer (males).

Exclusion Criteria

• Active viral infection based on clinical observations.

• The presence of SGCA 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%

• Serological evidence of HIV infection, or Hepatitis A, B or C infection

• Diagnosis of (or ongoing treatment for) an autoimmune disease

• Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm)

• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer

• Pregnancy

• Subjects with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by ELISA immunoassay