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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Mitochondrial Diseases
• Intervention / Treatment: Procedure: Bone Marrow mobilization; Procedure: Apheresis; Biological: MNV-BM-PLC infusion

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.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Eyal Shoshani; Phone Number: 972544758318; Email: eyal@minoviatx.com
• Study Contact Backup: Name: Lea Bensoussan; Phone Number: 972-58-610-1291; Email: lea@minoviatx.com

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center - Tel Ashomer
    • Contact: Elad Jacobi, MD; Phone Number: 972-3-5303037; Email: elad.jacoby@sheba.gov.il
    • Contact: Diana Chigalayev; Phone Number: 972-3-5307145; Email: diana.chigalayev@sheba.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cohort 1 & Cohort 2; 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; 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; Procedure: Apheresis; Apheresis will be performed two days prior to MNV-BM-PLC infusion. During this procedure, patient's peripheral blood will be collected by apheresis; Biological: MNV-BM-PLC infusion; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 years
Measurement of hemoglobin level	Change from baseline in hematological parameter	2 years
Measurement of absolute neutrophil count	Change from baseline in hematological parameter	2 years
Measurement of platelet count	Change from baseline in hematological parameter	2 years
IPMDS (International Pediatric Mitochondrial Disease Scale)	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	2 years
Performance Score	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	2 years
PEDI: Pediatric Evaluation of Disability Inventory	Stabilization or improvement in PEDI score relative to baseline	2 years
6-minute walk test	Stabilization or improvement in 6-minute walk test relative to baseline	2 years
30 Second chair stand	Stabilization or improvement in 30 Second chair stand relative to baseline	2 years
Hospitalization events	Reduction in number, cause and duration of hospitalization events relative to 12 months before IP treatment	1 year

Collaborators and Investigators

• Sponsor: Minovia Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Mitochondrial DNA Mutation or Deletion
• Additional Relevant MeSH Terms: Metabolic Diseases; Mitochondrial Diseases
• Other Study ID Numbers: PLC-PMD-01-IL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No