Clinical trial NCT04548843: 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
Official title: A First in Human Phase I, Open Label Dose-escalation 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Primary Mitochondrial Diseases
Keywords: Mitochondrial DNA Mutation or Deletion
Lead sponsor: Minovia Therapeutics Ltd.
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 6
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The study will involve two sequential cohorts:

Cohort 1: 3 patients will be administrated with Dose 1 The dosing interval between patients will be at minimum 2 weeks. Two (2) weeks after the 3rd patient has received MNV-BM-PLC, the Data safety monitoring board (DSMB) will convene to review accumulated safety data. The DSMB will make a recommendation whether to proceed with the 4th patient administration.

Cohort 2: 3 patients will be administrated with Dose 2 The dosing interval between patients will be at minimum 2 weeks.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Primary outcomes:
measure: Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
timeFrame: 1 month
measure: Measurement of hemoglobin level
timeFrame: 1 month
measure: Measurement of absolute neutrophil count
timeFrame: 1 month
measure: Measurement of platelet count
timeFrame: 1 month
Secondary outcomes:
measure: Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
timeFrame: 2 years
measure: Measurement of hemoglobin level
timeFrame: 2 years
measure: Measurement of absolute neutrophil count
timeFrame: 2 years
measure: Measurement of platelet count
timeFrame: 2 years
measure: IPMDS (International Pediatric Mitochondrial Disease Scale)
timeFrame: 2 years
measure: Performance Score
timeFrame: 2 years
measure: PEDI: Pediatric Evaluation of Disability Inventory
timeFrame: 2 years
measure: 6-minute walk test
timeFrame: 2 years
measure: 30 Second chair stand
timeFrame: 2 years
measure: Hospitalization events
timeFrame: 1 year
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - Tel Ashomer
Study officials:
References: