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.
Male or female participants aged from 1 to 18 years old.
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.
Participants have failure to thrive (height SDS smaller than -1)
Participants should have at least 12 months' history of body weight and height and calculated GFR (from creatinine) before treatment.
History of infection with HIV-1, HIV-2, or HTLV I/II.
Participants have any active infection.
Participants have been diagnosed with Myelodysplastic Syndrome, by FISH and/or karyotype.
Participants are unable to undergo apheresis.
Single group
MNV-201
Biological/VaccineAutologous 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.
Occurrence of treatment-related adverse events
Occurrence of treatment-related adverse events as assessed by CTCAE v5.0 following MNV-201 infusion
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.
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.
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)
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.
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.
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
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.
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