ATA-200 Dose-escalation Gene Therapy Trial in Patients With LGMDR5

Study Overview
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Brief Summary
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The purpose of ATA-003-GSAR study is to evaluate the safety and tolerability of a single intravenous infusion of ATA-200 in pediatric patients with limb girdle muscular dystrophy type 2c/R5 (LGMD R5). Patients will be treated sequentially in 2 dose-cohorts.

Detailed Description
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This is a multicenter Phase 1b assessing the safety and tolerability of 2 doses of ATA-200 for the treatment of LGMDR5. The dose escalation phase will enroll ambulant patients with LGMDR5. Two dose cohorts (C1) and (C2) will be enrolled sequentially and enrollment will be staggered with at least 4-week interval between 2 patient treatments. An initial cohort C1 of three (3) patients will receive a potentially effective dose corresponding to the minimum effective dose (MED) in preclinical studies. Enrollment of three (3) patients in the 2nd higher dose cohort C2 (with a 7-fold safety margin relative to the highest safe dose in the GLP toxicology study) will be initiated following review of the one-month safety data post-administration in cohort C1 by an independent Data Safety Monitoring Board (DSMB). Time point of primary interest for safety evaluation and dose selection for future studies is at 6 months. All subjects will be followed up for an additional 4.5 years after completion of the evaluation period.

Official Title
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A Phase 1-2, Open-label, Dose Escalation Study to Evaluate the Safety of 2 Doses of Intravenous ATA-200, an Adeno-associated Viral Vector Carrying the Human Gamma-sarcoglycan Gene, in Patients With Gamma-sarcoglycanopathy (Limb-girdle Muscular Dystrophy LGMDR5)

Conditions
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LGMD2C

Intervention / Treatment
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* Biological: ATA-200


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of LGMDR5 before age of 10, based on clinical presentation and genotyping Ambulant male or female patients aged 6 to less than 12 years of age at screening Able to perform the 10-meter walk test (10MWT) in less than 15 sec and to rise from chair with or without arm support Exclusion Criteria: Detectable neutralizing antibodies against AAV8 Cardiomyopathy with left ventricular ejection fraction (LVEF) < 50% Respiratory assistance Concomitant medical condition that might interfere with LGMDR5 evolution Acute illness within 4 weeks of anticipated IMP administration Current participation in another clinical trial with investigational medicinal product Previous participation in gene and cell therapy trials Any condition that would contraindicate immunosuppressant treatment Presence of any permanent items (e.g., metal braces) precluding undergoing MRI Any vaccination 1 month prior to planned IMP administration Serology consistent with HIV exposure or active hepatitis B or C infection Grade 2 or higher lab abnormalities for liver function tests, creatinine, hemogram and coagulation

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>ATA-200 Dose level 1: 1.0E+14 vg/Kg, solution for injection, single IV infusion over 2h | Biological: ATA-200<br>* single intravenous infusion<br>|
| Experimental: Cohort 2<br>ATA-200 Dose level 2: 3.0E+14 vg/Kg, solution for injection, single IV infusion over 2h | Biological: ATA-200<br>* single intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Collection of adverse events at each visit | 0-6 months | 
| Incidence of treatment-emergent adverse events, | Collection of adverse events at each visit | 0-6 months | 
| Incidence of serious adverse events | Collection of adverse events at each visits | 0-6 months |