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

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

Sponsors

Lead Sponsor: Minovia Therapeutics Ltd.

Source 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.

Overall Status Not yet recruiting
Start Date January 2021
Completion Date January 2024
Primary Completion Date January 2022
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC 1 month
Measurement of hemoglobin level 1 month
Measurement of absolute neutrophil count 1 month
Measurement of platelet count 1 month
Secondary Outcome
Measure Time Frame
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
Performance Score 2 years
PEDI: Pediatric Evaluation of Disability Inventory 2 years
6-minute walk test 2 years
30 Second chair stand 2 years
Hospitalization events 1 year
Enrollment 6
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Bone Marrow mobilization

Description: 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

Arm Group Label: Cohort 1 & Cohort 2

Intervention Type: Procedure

Intervention Name: Apheresis

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

Arm Group Label: Cohort 1 & Cohort 2

Intervention Type: Biological

Intervention Name: MNV-BM-PLC infusion

Description: 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.

Arm Group Label: Cohort 1 & Cohort 2

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.

Gender: All

Minimum Age: 4 Years

Maximum Age: 18 Years

Healthy Volunteers: No

Overall Contact

Last Name: Eyal Shoshani

Phone: 972544758318

Email: [email protected]

Location
Facility: Contact: Contact Backup: Sheba Medical Center - Tel Ashomer Elad Jacobi, MD 972-3-5303037 [email protected]
Location Countries

Israel

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Cohort 1 & Cohort 2

Type: Experimental

Description: 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).

Study Design Info

Intervention Model: Sequential Assignment

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

Masking: None (Open Label)

Source: ClinicalTrials.gov