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

NCT04548843 | Withdrawn Phase 1 DMC

• 1 other identifier: PLC-PMD-01-IL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Mitochondrial Diseases

Keywords

Mitochondrial DNA Mutation or Deletion

Outcome Measures

Primary Outcomes (4)

• Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC

  Severity will graded according to CTCAE, Version 5.0

  1 month

• Measurement of hemoglobin level

  Change from baseline in hematological parameter

  1 month

• Measurement of absolute neutrophil count

  Change from baseline in hematological parameter

  1 month

• Measurement of platelet count

  Change from baseline in hematological parameter

  1 month

Secondary Outcomes (10)

• Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC

  2 years

• Measurement of hemoglobin level

  2 years

• Measurement of absolute neutrophil count

  2 years

• Measurement of platelet count

  2 years

• IPMDS (International Pediatric Mitochondrial Disease Scale)

  2 years

Study Arms (1)

Cohort 1 & Cohort 2

EXPERIMENTAL

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).

Procedure: Bone Marrow mobilization; Procedure: Apheresis; Biological: MNV-BM-PLC infusion

Interventions

Bone Marrow mobilization PROCEDURE

During four days before the apheresis, Neupogen (G-CSF) at a dose of 10 microgram per kilogram will be administered subcutaneously in the morning (days -6 to -3 of cell therapy). In addition, Mozobil (Plerixafor) at a dose of 0.24 milligram per kilogram will be administered subcutaneously approximately 4 hours before apheresis initiation. A fifth dose of Neupogen (G-CSF) will be administered just prior to the apheresis

Cohort 1 & Cohort 2

Apheresis PROCEDURE

Apheresis will be performed two days prior to MNV-BM-PLC infusion. During this procedure, patient's peripheral blood will be collected by apheresis

Cohort 1 & Cohort 2

MNV-BM-PLC infusion BIOLOGICAL

The MNV-BM-PLC (autologous CD34+ cells enriched with placenta-derived allogeneic mitochondria) infusion will be performed by standard IV procedure. The dosing interval between patients will be at minimum 2 weeks.

Cohort 1 & Cohort 2

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Minovia Therapeutics Ltd.: lead

Study Sites (1)

Sheba Medical Center - Tel Ashomer

Ramat Gan, Israel

Location

MeSH Terms

Interventions

Blood Component Removal

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: March 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

IL (1)