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

Sponsor

Minovia Therapeutics Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT03384420

Collaborator

(none)

Enrollment

Location

Arm

24.8

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mitochondrial Diseases Pearson Syndrome	Biological: CD34+ cells enriched with MNV-BLD	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 13, 2019

Actual Primary Completion Date :

Mar 9, 2021

Actual Study Completion Date :

Mar 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention CD34+ cells enriched with MNV-BLD 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)

Arm

Intervention/Treatment

Experimental: Intervention CD34+ cells enriched with MNV-BLD

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)

Outcome Measures

Primary Outcome Measures

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. [1 year]
Severity will graded according to CTCAE, Version 5.0
IPMDS (International Pediatric Mitochondrial Disease Scale) [1 year]
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

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Patient diagnosed with Pearson Syndrome, as verified by molecular identification of a defect in the mitochondrial DNA.
Normal maternal mitochondria as verified by mtDNA sequencing.
Males and females between 3 years or older and up to 18th birthday.
Patient is transfusion independent.
Patient has at least one of the following systematic involvements:
High baseline lactate levels
Episodes of metabolic crisis in the last year before pre-screening
Renal failure (not dependent on dialysis) or evidence of proximal tubulopathy
Growth retardation or failure to thrive

Exclusion Criteria

Absence of detectable mitochondria mutation or deletion.
Patient or patient's mother have a positive test for microbiologic
Patient is unable to undergo leukapheresis.
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.
Patient has been treated previously with any cell or gene therapy.
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.