LGMD
Conditions
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.
Interventions
BIOLOGICALGenPHSat injection (Safety)
Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the left biceps muscle.
BIOLOGICALGenPHSat injection (Efficacy)
Participants receive gene edited primary human muscle stem cells (GenPHsat) injection in the right biceps muscle.
OTHERMuscle Biopsy (Safety)
Participants undergo muscle biopsy 3 month after safety GenPHSat injection.
Sponsors
Simone Spuler, MD
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of Muscle force | Until 6 month post injection | Muscle force measurement data taken at screening (baseline), visit 1, 2, 3 and 4 (end of trial). |
| Rate of Blood CK | Until 6 month post injection | CK blood determination at screening (baseline), visit 1, 2, 3 and 4 (end of trial). |
Contacts
Primary ContactSimone Spuler, Prof Dr med
Backup ContactChristian Witzel, Dr med
Outcome results
None listed