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

• ClinicalTrials.gov Identifier: NCT05588401
• Recruitment Status: Not yet recruiting
• First Posted: October 20, 2022
• Last Update Posted: August 3, 2023
• Sponsor: Simone Spuler, MD
• Information provided by (Responsible Party): Simone Spuler, MD, Charite University, Berlin, Germany

Study Description

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.

Condition or disease	Intervention/treatment	Phase
LGMD	Biological: GenPHSat injection (Safety); Biological: GenPHSat injection (Efficacy); Other: Muscle Biopsy (Safety)	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase 1/2a First-in-human Trial Evaluating Autologous Gene-edited Muscle Stem Cells in Limb Girdle Muscular Dystrophies (GenPHSats-bASKet)
• Estimated Study Start Date: July 1, 2024
• Estimated Primary Completion Date: July 1, 2025
• Estimated Study Completion Date: July 1, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 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 :

1. Rate of muscle biopsy post-injection structure [ Time Frame: 3 month post injection ]
   The muscle biopsy taken and stained to visualize muscle biopsy structure after 3 month post injection.

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 14 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Simone Spuler, Prof Dr med; 004930450540501; simone.spuler@charite.de

Contact: Christian Witzel, Dr med; +49 30 553016; christian.witzel@charite.de

Sponsors and Collaborators

Simone Spuler, MD

Investigators

• Study Chair: Simone Spuler, Prof Dr med; Charite Universitätsmedizin Berlin, Germany

More Information

• Responsible Party: Simone Spuler, MD, Clinical Professor, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT05588401
• Other Study ID Numbers: bASKet
• First Posted: October 20, 2022
• Last Update Posted: August 3, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No