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

Phase 1/2a First-in-human Trial Evaluating Autologous Gene-edited Muscle Stem Cells in Limb Girdle Muscular Dystrophies (GenPHSats-bASKet)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: LGMD
• Intervention / Treatment: Biological: GenPHSat injection (Safety); Biological: GenPHSat injection (Efficacy); Other: Muscle Biopsy (Safety)

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

Contacts and Locations

• Study Contact: Name: Simone Spuler, Prof Dr med; Phone Number: 004930450540501; Email: simone.spuler@charite.de
• Study Contact Backup: Name: Christian Witzel, Dr med; Phone Number: +49 30 553016; Email: christian.witzel@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GenPHSat safety injection and GenPHSat efficacy injection; Initial intervention with six injections into the left biceps. A second intervention with 36 injections into the right biceps.

Biological: GenPHSat injection (Safety); Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the left biceps muscle.; Biological: GenPHSat injection (Efficacy); Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the right biceps muscle.; Other: Muscle Biopsy (Safety); Participants undergo muscle biopsy 3 month after safety GenPHSat injection.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of muscle biopsy post-injection structure	The muscle biopsy taken and stained to visualize muscle biopsy structure after 3 month post injection.	3 month post injection

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Muscle force	Muscle force measurement data taken at screening (baseline), visit 1, 2, 3 and 4 (end of trial).	Until 6 month post injection
Rate of Blood CK	CK blood determination at screening (baseline), visit 1, 2, 3 and 4 (end of trial).	Until 6 month post injection

Collaborators and Investigators

• Sponsor: Simone Spuler, MD
• Investigators: Study Chair: Simone Spuler, Prof Dr med, Charite Universitätsmedizin Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: bASKet

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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