A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome

A Phase I/II, Open Label, Single Dose Clinical Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD (Autologous cd34+ Cells Enriched With Blood Derived Mitochondria) in Pediatric Patients With Pearson Syndrome

Mitochondrial diseases are a genetically heterogeneous group of disorders caused by mutations or deletions in mitochondrial DNA (mtDNA) displaying a wide range of severity and phenotypes. These diseases may be inherited from the mother (mitochondrial inheritance) or non-inherited. The latter are ultra-rare pediatric diseases caused by a mutation or deletion of mtDNA, which develop into a systemic multi organ disease and eventually death. MNV-BM-BLD is a therapeutic process for enrichment of patient's peripheral hematopoietic stem cells with normal and healthy mitochondria derived from donor blood cells. The process, called mitochondria augmentation therapy, aims to reduce the symptoms of mitochondrial diseases.

Study Overview

• Status: Completed
• Conditions: Mitochondrial Diseases; Pearson Syndrome
• Intervention / Treatment: Biological: CD34+ cells enriched with MNV-BLD

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center Hospital- Tel Hashomer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Patient diagnosed with Pearson Syndrome, as verified by molecular identification of a defect in the mitochondrial DNA.
2. Normal maternal mitochondria as verified by mtDNA sequencing.
3. Males and females between 3 years or older and up to 18th birthday.
4. Patient is transfusion independent.

5. Patient has at least one of the following systematic involvements:

   1. High baseline lactate levels
   2. Episodes of metabolic crisis in the last year before pre-screening
   3. Renal failure (not dependent on dialysis) or evidence of proximal tubulopathy
   4. Growth retardation or failure to thrive

Exclusion Criteria

1. Absence of detectable mitochondria mutation or deletion.
2. Patient or patient's mother have a positive test for microbiologic
3. Patient is unable to undergo leukapheresis.
4. Patient suffers from chronic severe infection, malignant disease or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results.
5. Patient has been treated previously with any cell or gene therapy.
6. Patient has participated in another clinical treatment trial or received other experimental medications outside of a clinical trial within 1 month prior to start of this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention CD34+ cells enriched with MNV-BLD	Biological: CD34+ cells enriched with MNV-BLD; Transplantation of autologous stem cell enriched with MNV-BLD (blood-derived mitochondria)

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-BLD during a follow up period of 12 months post treatment.	Severity will graded according to CTCAE, Version 5.0	1 year
IPMDS (International Pediatric Mitochondrial Disease Scale)	To compare the change in International Pediatric Mitochondrial Disease Scale (IPMDS) score during a follow up period of 12 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	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	To compare the changes (kilograms) to Baseline	1 year
Quantification of levels of normal mtDNA in blood and urine	To compare the changes to Baseline	1 years
Metabolic crisis events occurrence compared to two years prior to the study.	To compare the changes during 3 years (2 years prior the study entry and 1 year follow up)	3 Years
Change in renal function	Measurement of blood creatinine in a serum sample	1 year
Change in Brain involvement	Lactate peak as assessed by MRS	1 year
Height	To compare the changes (in meters) to Baseline	1 year
Change in cardiac function	Assessment of left ventricular ejection fraction via echocardiography	1 year
Monitoring for liver disease	Measurement of Aspartate Aminotransferase and Alanine aminotransferase level	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization events	To compare the changes from medical history to 1 year follow up	1 year
Change in functional status	Distance traveled during the 6MWT (meters)	1 year
Change in hematological parameter	Measurement of hemoglobin level	1 year
Change in hematological parameter	Measurement of absolute neutrophil count	1 year
Change in hematological parameter	Measurement of platelet count	1 year
Control of blood glucose concentration	Hemoglobin A1c% in whole blood	1 year
ATP content.	To compare the changes to Baseline	1 year

Collaborators and Investigators

• Sponsor: Minovia Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2019
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: December 24, 2017
• First Posted (Actual): December 27, 2017

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Rare Diseases; Autologous stem cell transplantation; Mitochondrial Diseases; Pearson Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Musculoskeletal Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Syndrome; Mitochondrial Diseases; Muscular Diseases; Lipid Metabolism, Inborn Errors
• Other Study ID Numbers: MNV-BM-BLD-001-IL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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