Clinical trial NCT03384420: A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mitochondrial Diseases
Pearson Syndrome
Keywords: Autologous stem cell transplantation
Mitochondrial Diseases
Pearson Syndrome
Rare Diseases
Lead sponsor: Minovia Therapeutics Ltd.
Sponsor class: INDUSTRY
First posted: 2017-12-27
Enrollment: 7
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

1. Patient diagnosed with Pearson Syndrome, as verified by molecular identification of a defect in the mitochondrial DNA.
2. Normal maternal mitochondria as verified by mtDNA sequencing.
3. Males and females between 3 years or older and up to 18th birthday.
4. Patient is transfusion independent.
5. Patient has at least one of the following systematic involvements:

   1. High baseline lactate levels
   2. Episodes of metabolic crisis in the last year before pre-screening
   3. Renal failure (not dependent on dialysis) or evidence of proximal tubulopathy
   4. Growth retardation or failure to thrive

Exclusion Criteria

1. Absence of detectable mitochondria mutation or deletion.
2. Patient or patient's mother have a positive test for microbiologic
3. Patient is unable to undergo leukapheresis.
4. 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.
5. Patient has been treated previously with any cell or gene therapy.
6. 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.

Primary outcomes:
measure: 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.
timeFrame: 1 year
measure: IPMDS (International Pediatric Mitochondrial Disease Scale)
timeFrame: 1 year
Secondary outcomes:
measure: Weight
timeFrame: 1 year
measure: Quantification of levels of normal mtDNA in blood and urine
timeFrame: 1 years
measure: Metabolic crisis events occurrence compared to two years prior to the study.
timeFrame: 3 Years
measure: Change in renal function
timeFrame: 1 year
measure: Change in Brain involvement
timeFrame: 1 year
measure: Height
timeFrame: 1 year
measure: Change in cardiac function
timeFrame: 1 year
measure: Monitoring for liver disease
timeFrame: 1 year
Other outcomes:
measure: Hospitalization events
timeFrame: 1 year
measure: Change in functional status
timeFrame: 1 year
measure: Change in hematological parameter
timeFrame: 1 year
measure: Change in hematological parameter
timeFrame: 1 year
measure: Change in hematological parameter
timeFrame: 1 year
measure: Control of blood glucose concentration
timeFrame: 1 year
measure: ATP content.
timeFrame: 1 year
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Hospital- Tel Hashomer
Study officials:
References: