Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)

PHASE II, OPEN LABEL, SINGLE DOSE STUDY OF THE SAFETY AND EFFICACY OF MNV-201 FOR THE TREATMENT OF PEARSON SYNDROME

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.

Study Overview

• Status: Recruiting
• Conditions: Mitochondrial Diseases; Pearson Syndrome
• Intervention / Treatment: Biological: MNV-201

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lea Bensoussan, Msc; Phone Number: +972 + 972 586101291; Email: lea@minoviatx.com
• Study Contact Backup: Name: Natalie Yivgi Ohana, PhD; Phone Number: +972 +972 54 5833727; Email: natalie@minoviatx.com

Study Locations

• Israel
  • Ramat Gan, Israel, 5266202
    • Recruiting
    • Sheba Medical Center
    • Contact: Elad Jacoby, MD; Phone Number: +972 526668355; Email: elad.jacoby@sheba.health.gov.il
    • Contact: Moran Levin; Phone Number: +972523923147; Email: moran.levin@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants aged from 1 to 18 years old.
2. Diagnosis of Pearson Syndrome (current or history) as verified by molecular identification of deletion in mtDNA of peripheral blood. Participants are diagnosed with PS Participant can be in either the PS manifestations of the disease or may have transitioned to Kearns Sayre Syndrome (KSS) manifestations but has a history of PS.
3. Participants have failure to thrive (height SDS smaller than -1)
4. Participants should have at least 12 months' history of body weight and height and calculated GFR (from creatinine) before treatment.
5. Body weight ≥ 10 kg.
6. Participants' living parent(s) and/or legal guardian(s) able to understand and provide voluntary written informed consent.
7. Participants' parents or legal guardian have a good understanding of the study and nature of the procedure and are expected to be able to comply with study visit schedules and caregiver assessments without difficulty.
8. Participants' parents or legal guardian provides written informed consent prior to study participation.
9. Participants are medically able to undergo the study interventions as determined by the Investigator.

Exclusion criteria:

1. History of infection with HIV-1, HIV-2, or HTLV I/II.
2. Participants have any active infection.
3. Participants have been diagnosed with Myelodysplastic Syndrome, by FISH and/or karyotype.
4. Participants are unable to undergo apheresis.
5. Participants have known hypersensitivity to murine proteins or iron-dextran.
6. Participants have severe chronic infection.
7. Participants have disease or conditions that may risk the participant or interfere with the ability to interpret the study results.
8. History of malignancy.
9. History of treatment with gene therapy, allogeneic bone marrow or cord blood transplantation.
10. Participants have had a change in growth hormone regimen in less than 2 years prior to treatment.
11. Participants have participated in another clinical trial or received other experimental medications outside a clinical trial within 1 month prior to start of this study.
12. Participants who are pregnant or intend to become pregnant in the next 12 months.
13. In the opinion of the Investigator, the participant is unsuitable for participating in the study for any reason.

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: Autologous CD34+ cells enriched with allogenic placenta-derived mitochondria	Biological: MNV-201; 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.; Other Names: CD34+ cells enriched with allogeneic placenta derived mitochondria

What is the study measuring?

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.
Height SDS	Improvement from baseline to 12 months post treatment in height SDS compared to the calculated change in height SDS in the 12 months prior to treatment.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height SDS	Improvement from baseline to 6 months post treatment in height SDS compared to the calculated change in height SDS in the 6 months prior to treatment.	12 months
Calculated GFR Slope	Improvement in calculated GFR slope 6- and/or 12-months post treatment relative to 6 and/or 12 months prior to treatment (respectively)	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoint: Organ dysfunction	Improvement in any of the measurements below of organ dysfunction at 6- and/or 12-month post-treatment compared to Baseline; Renal glomerulopathy measured by level of cystatin-C or creatinine; Renal tubulopathy measured by urine amino acids; Renal tubulopathy measured by blood bicarbonate; Gastrointestinal activity measured by albumin; Gastrointestinal activity measured by pediatric PedsQL 3.0 Gastrointestinal Symptoms Module; Pancreas activity measured by insulin; Pancreas activity measured by C-peptide; Heart activity measured by ECG; Growth measured by GDF15; Growth measured by IGF1; Growth measured by IGFBP; Change in physician organ involvement score (see appendix C); Renal glomerulopathy measured by slope of change in eGFR calculated from cystatin-C at 6- or 12-month post-treatment compared to that calculated in the 6- or 12- month period prior to baseline.	24 months
Exploratory endpoint: IPMDS	Improvement from baseline in normalized International Pediatric Mitochondrial Disease Scale (IPMDS) scores (total score or each of three separate components) at 6- or 12-month post-treatment compared to Baseline.	12 months
Exploratory endpoint: Frequency of Hospitalizations	Reduction in frequency of hospitalization(s) during the 6- and/or 12-months post treatment relative to the 6 and/or 12 months (respectively) prior to treatment	24 months
Exploratory endpoint: Length of Hospitalizations	Reduction of length of hospitalization(s) during the 6- and/or 12-months post treatment relative to the 6 and/or 12 months (respectively) prior to treatment.	24 months
Exploratory endpoint: exogenous mtDNA	Pharmacokinetic measurements: exogenous mtDNA analysis in PBMCs at 6- and/or 12-month time points	12 months
Exploratory endpoint: Blood based biomarkers	Change in blood-based biomarkers at 6- and/or 12-month post-treatment compared to Baseline; Mitochondrial quantity and activity (full length mtDNA copy number in PBMC and/or whole blood); ATP content of PBMCs;; Anti-mitochondrial antibody level; PBMC subset analysis.	12 months
Exploratory endpoint: Height SDS	Improvement in height SDS at 6 and/or 12 months relative to natural history available (prospective and/or retrospective)	12 months
Exploratory endpoint: weight SDS	Improvement in weight SDS in 6-month and/or 12-month period after treatment relative to 6- and/or 12-month period (respectively) prior to treatment.	24 months

Collaborators and Investigators

• Sponsor: Minovia Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Transplantation; Autologous; Stem cell; Mitochondrial; Pearson
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Disease; Lipid Metabolism Disorders; Syndrome; Muscular Diseases; Mitochondrial Diseases; Lipid Metabolism, Inborn Errors
• Other Study ID Numbers: MNV-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No