Gene Transfer Clinical Trial for LGMD2E (Beta-sarcoglycan Deficiency) Using scAAVrh74.MHCK7.hSGCB

• Status: Recruiting
• Trial end date: 2020-12-31
• Target enrollment: 9
• Participant gender: All

Summary

The proposed clinical trial is the first-in-human, randomized, double-blinded, single dose study of self-complementary AAVrh.74 carrying the human β-sarcoglycan gene under the control of an MHCK7 promoter (scAAVrh74.MHCK7.hSGCB) delivered through a single systemic injection in a peripheral vein of LGMD2E. Nine total subjects (6 treated, 3 placebo) will be enrolled.

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

Details

• Lead Sponsor: Jerry R. Mendell
• Collaborator: Myonexus Therapeutics

Criteria

INCLUSION CRITERIA

• Subjects ages 4 through age 15, inclusive

• Males or females of any ethnic group

• SGCB DNA gene mutations at both alleles.

• Weakness demonstrated based on history of difficulty running, jumping and climbing stairs.

• 100m timed test: ≥40% of predicted for age, height and weight matched healthy controls at the screening visit.

• 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.

EXCLUSION CRITERIA

Individuals who meet the following exclusion criteria will not be eligible to participate in the study:

• Active viral infection based on clinical observations.

• Cardiac MRI determined ejection fraction <40%

• Serological evidence of HIV infection, or Hepatitis 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 binding antibody titers > 1:400 as determined by ELISA immunoassay. If endpoint titer is positive at screening, testing may be repeated in 1 month.

• Has a medical condition or circumstance that could compromise the protocol compliance or compromise safety

• Severe infection (e.g. pneumonia, pyelonephritis, or meningitis) within 4 weeks before gene transfer visit (enrollment may be postponed).

• Family does not want to disclose patient's study participation with primary care physician and other medical providers.