A First in Human Study to Evaluate the Safety of Infusion of MNV-BM-PLC (Autologous CD34+ Cells Enriched With Placenta Derived Allogeneic Mitochondria) in Patients With Primary Mitochondrial Diseases Associated With Mitochondrial DNA Mutation or Deletion
- Conditions
- Primary Mitochondrial Diseases
- Interventions
- Procedure: Bone Marrow mobilizationProcedure: ApheresisBiological: MNV-BM-PLC infusion
- Registration Number
- NCT04548843
- Lead Sponsor
- Minovia Therapeutics Ltd.
- Brief Summary
The study objectives are to evaluate the safety of a single intravenous (IV) infusion of autologous CD34+ cells enriched with placenta-derived allogeneic mitochondria in participant with primary mitochondrial disease associated with mitochondrial DNA mutations or deletions.
6 participants aged from 4 to 18 years old on the day of screening visit with primary mitochondrial disease associated with mitochondrial DNA mutations or deletions will be enrolled.
- Detailed Description
MNV-BM-PLC is a personalized cell therapy based on autologous patient-derived Hematopoietic stem/progenitor cells (HSPCs) enriched with mitochondria isolated from healthy placenta obtained from donors during C-section. Healthy mitochondria are employed, ex-vivo, to enrich the patient's CD34+ peripheral blood cells, followed by infusion of the mitochondrial enriched cells back to the patient. This therapeutic process of mitochondrial augmentation provides the patient with healthy mitochondria carrying non-mutated/deleted mtDNA that can supplement mitochondrial functionality in the patient's cells.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 6
- Molecular diagnosis of primary mitochondrial disease
- Age between 4 years and up to 18 years, with a minimum body weight of 20 (+/-1) kilogram on the day of screening visit.
- Performance score: Karnofsky ≥40 (or equivalent in children younger than 16 years old.
- Patients or Patient's parents or legal guardian (where applicable) has a good understanding of the study and nature of the procedure and is willing and able to provide written informed consent prior to participation in any study-related procedures.
- Medical ability to undergo the study procedures safely, as determined by the investigator.
Exclusion Criteria
- Positive test for pathogenic agents .
- Inability to undergo leukapheresis, as determined by the investigator.
- Chronic severe infection or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results.
- Known history of malignancy.
- Patient has been treated within the last one year prior to IP treatment with a different cell therapy.
- Patient has participated in another interventional clinical study and/or received other experimental medication outside of a clinical study within 1 month prior the day of Investigation product (IP) treatment visit.
- A pregnant or lactating woman or a woman who plans to become pregnant during the study. In addition, any woman of childbearing potential (not sterile or postmenopausal), who is unwilling to adhere to the use highly effective contraception method for the duration of the study
- In the opinion of the Investigator, the patient is unsuitable for participating in the study due to safety concerns.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 & Cohort 2 Bone Marrow mobilization 3 patients will be administrated with Dose 1 (0.88 mitochondria unit (mU) citrate synthase (CS) activity per million cells). 3 patients will be administrated with Dose 2 (4.4mU mitochondria unit (mU) citrate synthase (CS) activity per million cells). Cohort 1 & Cohort 2 Apheresis 3 patients will be administrated with Dose 1 (0.88 mitochondria unit (mU) citrate synthase (CS) activity per million cells). 3 patients will be administrated with Dose 2 (4.4mU mitochondria unit (mU) citrate synthase (CS) activity per million cells). Cohort 1 & Cohort 2 MNV-BM-PLC infusion 3 patients will be administrated with Dose 1 (0.88 mitochondria unit (mU) citrate synthase (CS) activity per million cells). 3 patients will be administrated with Dose 2 (4.4mU mitochondria unit (mU) citrate synthase (CS) activity per million cells).
- Primary Outcome Measures
Name Time Method Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC 1 month Severity will graded according to CTCAE, Version 5.0
Measurement of platelet count 1 month Change from baseline in hematological parameter
Measurement of hemoglobin level 1 month Change from baseline in hematological parameter
Measurement of absolute neutrophil count 1 month Change from baseline in hematological parameter
- Secondary Outcome Measures
Name Time Method 30 Second chair stand 2 years Stabilization or improvement in 30 Second chair stand relative to baseline
Hospitalization events 1 year Reduction in number, cause and duration of hospitalization events relative to 12 months before IP treatment
Measurement of platelet count 2 years Change from baseline in hematological parameter
Measurement of hemoglobin level 2 years Change from baseline in hematological parameter
Measurement of absolute neutrophil count 2 years Change from baseline in hematological parameter
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC 2 years Severity will graded according to CTCAE, Version 5.0
IPMDS (International Pediatric Mitochondrial Disease Scale) 2 years To compare the change in International Pediatric Mitochondrial Disease Scale (IPMDS) score during a follow up period of 3, 6 12 and 24 months post treatment. IPMDS total score ranges from 0 to 243. The score is expressed as the percentage of items which were feasible to perform. The lower the score is, the higher the child's function
Performance Score 2 years Stabilization or improvement in performance score (Lansky score (for patients younger than 15 years) or Karnofsky (for patients older than 15) score relative to baseline
PEDI: Pediatric Evaluation of Disability Inventory 2 years Stabilization or improvement in PEDI score relative to baseline
6-minute walk test 2 years Stabilization or improvement in 6-minute walk test relative to baseline
Trial Locations
- Locations (1)
Sheba Medical Center - Tel Ashomer
🇮🇱Ramat Gan, Israel