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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Mitochondrial Diseases, Pearson Syndrome

Intervention / Treatment
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* Biological: CD34+ cells enriched with MNV-BLD


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous stem cell transplantation, Mitochondrial Diseases, Pearson Syndrome, Rare Diseases