Evaluating Safety and Efficacy of Autologous Gene-edited Muscle Stem Cells (GenPHSats-bASKet)

Phase 1

Not yet recruiting

• Conditions: LGMD
• Interventions: Biological: GenPHSat injection (Safety); Biological: GenPHSat injection (Efficacy); Other: Muscle Biopsy (Safety)

• Registration Number: NCT05588401
• Lead Sponsor: Simone Spuler, MD

Brief Summary

This study is an investigator initiated first-in-human interventional open label phase 1/2a clinical trial investigating an ATMP in the orphan disease LGMD to evaluate safety and efficacy.

Detailed Description

This trial is directed towards a first-in-human application of GenPHSats; gene edited primary human satellite cell derived muscle stem cells as a new Advanced Therapy Medicinal Product (ATMP) in a phase 1/2a clinical trial with Gene edited PHSats (GenPHSats) initiating healthy muscle development in patients with LGDM. The trial is set up to verify if GenPHSats can provide an therapy option for LGDM patients as there is currently no therapy available. The GenPHSats are an autologous product comprised of primary human satellite cell derived muscle stem cells obtained from the patient's own muscle tissue and gene edited in vitro prior to transplantation.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-18
• Study First Posted: 2022-10-20
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-02
• Last Update Posted: 2023-08-03
• Study Start: 2024-07-01
• Primary Completion: 2025-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• LGDM diagnosed,
• Identified gene defect location and gene editing proved feasible,
• Age ≥14 years,
• Patient in treatment in the department at Charité, Universitätsmedizin Berlin, Muscle Research Unit and Outpatient Clinic for Muscle Disorders,
• Signed informed consent

Exclusion Criteria

• Acute or chronic inflammatory local or systemic disease
• Coagulation disorder
• Known complications due to local anesthesia,
• Congenital heart defect, cardiac arrhythmia,
• Pathology of the airways such as micrognathia
• Pierre Robin Sequence
• Central hypoventilation syndrome/Ondine syndrome
• Significant other medical or psychiatric illness
• Positive serology for HIV and/or hepatitis A, B, C
• Pregnant or lactating women
• Known allergic reaction to constituents of the cryopreservation medium

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
GenPHSat safety injection and GenPHSat efficacy injection	GenPHSat injection (Efficacy)	Initial intervention with six injections into the left biceps. A second intervention with 36 injections into the right biceps.
GenPHSat safety injection and GenPHSat efficacy injection	Muscle Biopsy (Safety)	Initial intervention with six injections into the left biceps. A second intervention with 36 injections into the right biceps.
GenPHSat safety injection and GenPHSat efficacy injection	GenPHSat injection (Safety)	Initial intervention with six injections into the left biceps. A second intervention with 36 injections into the right biceps.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Through study completion, an average of 1 year	Characterization of type, incidence, severity, duration, reversibility, treatability of adverse events recorded at least at visit 1, 2, 3 and 4 (end of trial).

Secondary Outcome Measures

Name	Time	Method
Rate of muscle biopsy post-injection structure	3 month post injection	The muscle biopsy taken and stained to visualize muscle biopsy structure after 3 month post injection.