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

Mitochondrial Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03384420
• Other study ID #: MNV-BM-BLD-001-IL
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 13, 2019
• Est. completion date: March 9, 2021

Study information

• Verified date: June 2020
• Source: Minovia Therapeutics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: March 9, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lipid Metabolism, Inborn Errors
• Mitochondrial Diseases
• Muscular Diseases
• Pearson Syndrome
• Syndrome

Intervention

Biological:
• CD34+ cells enriched with MNV-BLD
Transplantation of autologous stem cell enriched with MNV-BLD (blood-derived mitochondria)

Locations

Country	Name	City	State
Israel	Sheba Medical Center Hospital- Tel Hashomer	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Minovia Therapeutics Ltd.

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospitalization events	To compare the changes from medical history to 1 year follow up	1 year
Other	Change in functional status	Distance traveled during the 6MWT (meters)	1 year
Other	Change in hematological parameter	Measurement of hemoglobin level	1 year
Other	Change in hematological parameter	Measurement of absolute neutrophil count	1 year
Other	Change in hematological parameter	Measurement of platelet count	1 year
Other	Control of blood glucose concentration	Hemoglobin A1c% in whole blood	1 year
Other	ATP content.	To compare the changes to Baseline	1 year
Primary	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
Primary	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	Weight	To compare the changes (kilograms) to Baseline	1 year
Secondary	Quantification of levels of normal mtDNA in blood and urine	To compare the changes to Baseline	1 years
Secondary	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
Secondary	Change in renal function	Measurement of blood creatinine in a serum sample	1 year
Secondary	Change in Brain involvement	Lactate peak as assessed by MRS	1 year
Secondary	Height	To compare the changes (in meters) to Baseline	1 year
Secondary	Change in cardiac function	Assessment of left ventricular ejection fraction via echocardiography	1 year
Secondary	Monitoring for liver disease	Measurement of Aspartate Aminotransferase and Alanine aminotransferase level	1 year