Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-201 in Pediatric Patients With Pearson Syndrome

Study Overview
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Brief Summary
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Primary Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders caused by mutations in genes encoded by nuclear Deoxyribonucleic Acid (DNA) or by mutations and/or deletions in the mitochondrial DNA (mtDNA). While some mitochondrial disorders only affect a single organ (e.g., the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organs. Mitochondrial disorders may present at any age and a frequent feature is the increasing number of organs involved in the course of the disease. Minovia Therapeutics Ltd. (Minovia) is a biotech company developing novel therapeutics based on its mitochondrial augmentation technology (MAT). MNV-201 is a cell therapy produced by MAT that consists of the participant's autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) enriched with allogeneic placental-derived mitochondria, manufactured in Minovia's GMP facility.

Official Title
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A Phase I, Open Label, Single Dose Clinical Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-201 (Autologous CD34+ Cells Enriched With Allogenic Placenta Derived Mitochondria) in Pediatric Patients With Pearson Syndrome

Conditions
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Mitochondrial Diseases, Pearson Syndrome

Intervention / Treatment
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* Biological: MNV-201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants aged from 1 to 18 years old. Diagnosis of Pearson Syndrome, mtDNA deletion verified by NGS. Body weight ≥ 10 kg. Participant has anemia or thrombocytopenia, or leukopenia and/or blood transfusion dependent (receives blood transfusions every 6 weeks or less). Participant is medically able to undergo the study interventions, as determined by the investigator. Participant's living parent(s) and/or legal guardian(s) able to understand and provide voluntary written informed consent. Exclusion Criteria: History of infection with HIV-1, HIV-2, or HTLV I/II. Current active infection with HBV (including HBcore and HBsAg positive), HCV, HTLV I/II, Treponema Pallidum or HIV I-II Participant has been diagnosed with Myelodysplastic Syndrome, by FISH and/or karyotype. Participant is unable to undergo leukapheresis. Total number of CD34+ cells collected is lower than 20x106 cells Participant has known hypersensitivity to murine proteins or iron-dextran. Participant has chronic severe infection. Participant has disease or condition that may risk the participant or interfere with the ability to interpret the study results. History of malignancy History of treatment with gene therapy, bone marrow or allogeneic cord blood transplantation. Currently participating in another clinical trial, or participation in another clinical trial within 1 year prior to study enrollment. In the opinion of the Investigator, the participant is unsuitable for participating in the study for any reason.

Ages Eligible for Study
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Minimum Age: 1 Year
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: Autologous CD34+ cells enriched with allogenic placenta-derived mitochondria<br> | Biological: MNV-201<br>* Autologous CD34+ cells are isolated from the participant's peripheral blood after mobilization by leukapheresis. Allogeneic mitochondria are isolated under aseptic conditions from healthy donor placenta, cryopreserved and qualified before use.<br>* Other names: CD34+ cells enriched with allogeneic placenta derived mitochondria;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment-related adverse events | Occurrence of treatment-related adverse events as assessed by CTCAE v5.0 following MNV-201 infusion. | 12 months post treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stabilization or improvement in Quality of Life (QoL) questionnaire IPMDS (International Pediatric Mitochondrial Disease Scale) scores | The score is expressed as the percentage of items which were feasible to perform. The lower the score, the better is the child performance. | 12 months post treatment | 
| Reduction in frequency and lengths of hospitalization during the 12 months after MAT compared to the 12 months period before MAT |  | 12 months post treatment | 
| Changes in anemia during a follow up period of 12 months post treatment. | Changes since baseline in anemia during a follow up period of 12 months post treatment measured by Complete Blood Count. | 12 months post treatment. | 
| Changes in thrombocytopenia during a follow up period of 12 months post treatment | Changes since baseline in thrombocytopenia during a follow up period of 12 months post treatment measured by Complete Blood Count. | 12 months post treatment | 
| Changes in leukopenia during a follow up period of 12 months post treatment | Changes since baseline in leukopenia during a follow up period of 12 months post treatment measured by Complete Blood Count. | 12 months post treatment | 
| Changes in frequency of blood transfusions during a follow up period of 12 months post treatment. | Changes in frequency of blood transfusion will be assessed based on the number of blood transfusions received by the participant since baseline compared to the number of blood transfusions the participant received during the 6 months period pre screening. | 12 months post treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous, Mitochondrial, Pearson, Transplantation, Stem cell