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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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LGMD

Intervention / Treatment
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* Biological: GenPHSat injection (Safety)
* Biological: GenPHSat injection (Efficacy)
* Other: Muscle Biopsy (Safety)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 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: Other
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GenPHSat safety injection and GenPHSat efficacy injection<br>Initial intervention with six injections into the left biceps. A second intervention with 36 injections into the right biceps. | Biological: GenPHSat injection (Safety)<br>* Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the left biceps muscle.<br>Biological: GenPHSat injection (Efficacy)<br>* Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the right biceps muscle.<br>Other: Muscle Biopsy (Safety)<br>* Participants undergo muscle biopsy 3 month after safety GenPHSat injection.<br>|

What is the study measuring?
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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 |