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

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 SGCG Gene, in Patients With Gamma-sarcoglycanopathy (LGMDR5)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: LGMD2C
• Intervention / Treatment: Biological: ATA-200

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sophie Olivier; Email: s.olivier@atamyo.com
• Study Contact Backup: Name: Damien Bouvier; Phone Number: +33972662469; Email: d.bouvier@atamyo.com

Study Locations

• France
  • Paris, France
    • Hopital Trousseau
    • Contact: Marina Colella, MD, PhD; Phone Number: + 33 (0)1 71 73 80 42; Email: m.colella@institut-myologie.org
• Italy
  • Milano, Italy
    • Ospedale Maggiore Policlinico
    • Contact: Giacomo Pietro Comi, MD; Phone Number: +39 0255033802; Email: giacomo.comi@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Atamyo Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ATA-003-GSAR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No