Back to resultsA First in Human Study to Evaluate the Safety of Infusion of MNV-BM-PLC (Autologous CD34+ Cells Enriched With Placenta Derived Allogeneic Mitochondria) in Patients With Primary Mitochondrial Diseases Associated With Mitochondrial DNA Mutation or Deletion
Primary Purpose
Primary Mitochondrial Diseases
Status
Not yet recruiting
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
Bone Marrow mobilization
Apheresis
MNV-BM-PLC infusion
Sponsored by
About this trial
This is an interventional treatment trial for Primary Mitochondrial Diseases focused on measuring Mitochondrial DNA Mutation or Deletion
Eligibility Criteria
Inclusion Criteria:
- Molecular diagnosis of primary mitochondrial disease
- Age between 4 years and up to 18 years, with a minimum body weight of 20 (+/-1) kilogram on the day of screening visit.
- Performance score: Karnofsky ≥40 (or equivalent in children younger than 16 years old.
- Patients or Patient's parents or legal guardian (where applicable) has a good understanding of the study and nature of the procedure and is willing and able to provide written informed consent prior to participation in any study-related procedures.
- Medical ability to undergo the study procedures safely, as determined by the investigator.
Exclusion Criteria
- Positive test for pathogenic agents .
- Inability to undergo leukapheresis, as determined by the investigator.
- Chronic severe infection or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results.
- Known history of malignancy.
- Patient has been treated within the last one year prior to IP treatment with a different cell therapy.
- Patient has participated in another interventional clinical study and/or received other experimental medication outside of a clinical study within 1 month prior the day of Investigation product (IP) treatment visit.
- A pregnant or lactating woman or a woman who plans to become pregnant during the study. In addition, any woman of childbearing potential (not sterile or postmenopausal), who is unwilling to adhere to the use highly effective contraception method for the duration of the study
- In the opinion of the Investigator, the patient is unsuitable for participating in the study due to safety concerns.
Sites / Locations
- Sheba Medical Center - Tel Ashomer
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cohort 1 & Cohort 2
Arm Description
3 patients will be administrated with Dose 1 (0.88 mitochondria unit (mU) citrate synthase (CS) activity per million cells). 3 patients will be administrated with Dose 2 (4.4mU mitochondria unit (mU) citrate synthase (CS) activity per million cells).
Outcomes
Primary Outcome Measures
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Severity will graded according to CTCAE, Version 5.0
Measurement of hemoglobin level
Change from baseline in hematological parameter
Measurement of absolute neutrophil count
Change from baseline in hematological parameter
Measurement of platelet count
Change from baseline in hematological parameter
Secondary Outcome Measures
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Severity will graded according to CTCAE, Version 5.0
Measurement of hemoglobin level
Change from baseline in hematological parameter
Measurement of absolute neutrophil count
Change from baseline in hematological parameter
Measurement of platelet count
Change from baseline in hematological parameter
IPMDS (International Pediatric Mitochondrial Disease Scale)
To compare the change in International Pediatric Mitochondrial Disease Scale (IPMDS) score during a follow up period of 3, 6 12 and 24 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
Performance Score
Stabilization or improvement in performance score (Lansky score (for patients younger than 15 years) or Karnofsky (for patients older than 15) score relative to baseline
PEDI: Pediatric Evaluation of Disability Inventory
Stabilization or improvement in PEDI score relative to baseline
6-minute walk test
Stabilization or improvement in 6-minute walk test relative to baseline
30 Second chair stand
Stabilization or improvement in 30 Second chair stand relative to baseline
Hospitalization events
Reduction in number, cause and duration of hospitalization events relative to 12 months before IP treatment
Full Information
NCT ID
NCT04548843
First Posted
September 8, 2020
Last Updated
August 30, 2021
Sponsor
Minovia Therapeutics Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04548843
Brief Title
A First in Human Study to Evaluate the Safety of Infusion of MNV-BM-PLC (Autologous CD34+ Cells Enriched With Placenta Derived Allogeneic Mitochondria) in Patients With Primary Mitochondrial Diseases Associated With Mitochondrial DNA Mutation or Deletion
Official Title
A First in Human Phase I, Open Label Dose-escalation Study to Evaluate the Safety of Infusion of MNV-BM-PLC (Autologous CD34+ Cells Enriched With Placenta Derived Allogeneic Mitochondria) in Patients With Primary Mitochondrial Diseases Associated With Mitochondrial DNA Mutation or Deletion
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2022 (Anticipated)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Minovia Therapeutics Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study objectives are to evaluate the safety of a single intravenous (IV) infusion of autologous CD34+ cells enriched with placenta-derived allogeneic mitochondria in participant with primary mitochondrial disease associated with mitochondrial DNA mutations or deletions.
6 participants aged from 4 to 18 years old on the day of screening visit with primary mitochondrial disease associated with mitochondrial DNA mutations or deletions will be enrolled.
Detailed Description
MNV-BM-PLC is a personalized cell therapy based on autologous patient-derived Hematopoietic stem/progenitor cells (HSPCs) enriched with mitochondria isolated from healthy placenta obtained from donors during C-section. Healthy mitochondria are employed, ex-vivo, to enrich the patient's CD34+ peripheral blood cells, followed by infusion of the mitochondrial enriched cells back to the patient. This therapeutic process of mitochondrial augmentation provides the patient with healthy mitochondria carrying non-mutated/deleted mtDNA that can supplement mitochondrial functionality in the patient's cells.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mitochondrial Diseases
Keywords
Mitochondrial DNA Mutation or Deletion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
The study will involve two sequential cohorts:
Cohort 1: 3 patients will be administrated with Dose 1 The dosing interval between patients will be at minimum 2 weeks. Two (2) weeks after the 3rd patient has received MNV-BM-PLC, the Data safety monitoring board (DSMB) will convene to review accumulated safety data. The DSMB will make a recommendation whether to proceed with the 4th patient administration.
Cohort 2: 3 patients will be administrated with Dose 2 The dosing interval between patients will be at minimum 2 weeks.
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 & Cohort 2
Arm Type
Experimental
Arm Description
3 patients will be administrated with Dose 1 (0.88 mitochondria unit (mU) citrate synthase (CS) activity per million cells).
3 patients will be administrated with Dose 2 (4.4mU mitochondria unit (mU) citrate synthase (CS) activity per million cells).
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow mobilization
Intervention Description
During four days before the apheresis, Neupogen (G-CSF) at a dose of 10 microgram per kilogram will be administered subcutaneously in the morning (days -6 to -3 of cell therapy). In addition, Mozobil (Plerixafor) at a dose of 0.24 milligram per kilogram will be administered subcutaneously approximately 4 hours before apheresis initiation.
A fifth dose of Neupogen (G-CSF) will be administered just prior to the apheresis
Intervention Type
Procedure
Intervention Name(s)
Apheresis
Intervention Description
Apheresis will be performed two days prior to MNV-BM-PLC infusion. During this procedure, patient's peripheral blood will be collected by apheresis
Intervention Type
Biological
Intervention Name(s)
MNV-BM-PLC infusion
Intervention Description
The MNV-BM-PLC (autologous CD34+ cells enriched with placenta-derived allogeneic mitochondria) infusion will be performed by standard IV procedure.
The dosing interval between patients will be at minimum 2 weeks.
Primary Outcome Measure Information:
Title
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Description
Severity will graded according to CTCAE, Version 5.0
Time Frame
1 month
Title
Measurement of hemoglobin level
Description
Change from baseline in hematological parameter
Time Frame
1 month
Title
Measurement of absolute neutrophil count
Description
Change from baseline in hematological parameter
Time Frame
1 month
Title
Measurement of platelet count
Description
Change from baseline in hematological parameter
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Description
Severity will graded according to CTCAE, Version 5.0
Time Frame
2 years
Title
Measurement of hemoglobin level
Description
Change from baseline in hematological parameter
Time Frame
2 years
Title
Measurement of absolute neutrophil count
Description
Change from baseline in hematological parameter
Time Frame
2 years
Title
Measurement of platelet count
Description
Change from baseline in hematological parameter
Time Frame
2 years
Title
IPMDS (International Pediatric Mitochondrial Disease Scale)
Description
To compare the change in International Pediatric Mitochondrial Disease Scale (IPMDS) score during a follow up period of 3, 6 12 and 24 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
Time Frame
2 years
Title
Performance Score
Description
Stabilization or improvement in performance score (Lansky score (for patients younger than 15 years) or Karnofsky (for patients older than 15) score relative to baseline
Time Frame
2 years
Title
PEDI: Pediatric Evaluation of Disability Inventory
Description
Stabilization or improvement in PEDI score relative to baseline
Time Frame
2 years
Title
6-minute walk test
Description
Stabilization or improvement in 6-minute walk test relative to baseline
Time Frame
2 years
Title
30 Second chair stand
Description
Stabilization or improvement in 30 Second chair stand relative to baseline
Time Frame
2 years
Title
Hospitalization events
Description
Reduction in number, cause and duration of hospitalization events relative to 12 months before IP treatment
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Molecular diagnosis of primary mitochondrial disease
Age between 4 years and up to 18 years, with a minimum body weight of 20 (+/-1) kilogram on the day of screening visit.
Performance score: Karnofsky ≥40 (or equivalent in children younger than 16 years old.
Patients or Patient's parents or legal guardian (where applicable) has a good understanding of the study and nature of the procedure and is willing and able to provide written informed consent prior to participation in any study-related procedures.
Medical ability to undergo the study procedures safely, as determined by the investigator.
Exclusion Criteria
Positive test for pathogenic agents .
Inability to undergo leukapheresis, as determined by the investigator.
Chronic severe infection or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results.
Known history of malignancy.
Patient has been treated within the last one year prior to IP treatment with a different cell therapy.
Patient has participated in another interventional clinical study and/or received other experimental medication outside of a clinical study within 1 month prior the day of Investigation product (IP) treatment visit.
A pregnant or lactating woman or a woman who plans to become pregnant during the study. In addition, any woman of childbearing potential (not sterile or postmenopausal), who is unwilling to adhere to the use highly effective contraception method for the duration of the study
In the opinion of the Investigator, the patient is unsuitable for participating in the study due to safety concerns.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eyal Shoshani
Phone
972544758318
Email
eyal@minoviatx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lea Bensoussan
Phone
972-58-610-1291
Email
lea@minoviatx.com
Facility Information:
Facility Name
Sheba Medical Center - Tel Ashomer
City
Ramat Gan
Country
Israel
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elad Jacobi, MD
Phone
972-3-5303037
Email
elad.jacoby@sheba.gov.il
First Name & Middle Initial & Last Name & Degree
Diana Chigalayev
Phone
972-3-5307145
Email
diana.chigalayev@sheba.gov.il
12. IPD Sharing Statement
Learn more about this trial
A First in Human Study to Evaluate the Safety of Infusion of MNV-BM-PLC (Autologous CD34+ Cells Enriched With Placenta Derived Allogeneic Mitochondria) in Patients With Primary Mitochondrial Diseases Associated With Mitochondrial DNA Mutation or Deletion
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