Primary Mitochondrial DiseasesPhase 1NCT04548843
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
A Phase 1 study testing Bone Marrow mobilization, Apheresis and MNV-BM-PLC infusion in people with Primary Mitochondrial Diseases, run by Minovia Therapeutics Ltd. at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Primary Mitochondrial Diseases
- What is being tested?
- Bone Marrow mobilization, Apheresis and MNV-BM-PLC infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Mar 2022to 1 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Primary Mitochondrial Diseases
- Being tested
- Bone Marrow mobilization, Apheresis, MNV-BM-PLC infusion
- Keywords
- Mitochondrial DNA Mutation or Deletion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone Marrow mobilizationProcedure or surgery
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
ApheresisProcedure or surgery
Apheresis will be performed two days prior to MNV-BM-PLC infusion. During this procedure, patient's peripheral blood will be collected by apheresis
MNV-BM-PLC infusionBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 & Cohort 2 | Experimental | 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). Receives: Procedure: Bone Marrow mobilization; Procedure: Apheresis; Biological: MNV-BM-PLC infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 month
Measurement of hemoglobin level
Change from baseline in hematological parameter
Measured: 1 month
Measurement of absolute neutrophil count
Change from baseline in hematological parameter
Measured: 1 month
Measurement of platelet count
Change from baseline in hematological parameter
Measured: 1 month
Secondary outcomes (10)
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
Measured: 2 years
Measurement of hemoglobin level
Change from baseline in hematological parameter
Measured: 2 years
Measurement of absolute neutrophil count
Change from baseline in hematological parameter
Measured: 2 years
Measurement of platelet count
Change from baseline in hematological parameter
Measured: 2 years
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
Measured: 2 years
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
Measured: 2 years
PEDI: Pediatric Evaluation of Disability Inventory
Stabilization or improvement in PEDI score relative to baseline
Measured: 2 years
6-minute walk test
Stabilization or improvement in 6-minute walk test relative to baseline
Measured: 2 years
30 Second chair stand
Stabilization or improvement in 30 Second chair stand relative to baseline
Measured: 2 years
Hospitalization events
Reduction in number, cause and duration of hospitalization events relative to 12 months before IP treatment
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start1 Mar 2022
- Primary completion1 Dec 2024
- Study completion1 Dec 2024
Why it stopped: No recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Mitochondrial DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minovia Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04548843
- Sponsor's protocol ID
- PLC-PMD-01-IL
- Status last verified
- Jun 2025
- First submitted
- 8 Sep 2020
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04548843
- Acronym / sponsor ID
- PLC-PMD-01-IL
- Conditions
- Primary Mitochondrial Diseases
- Keywords
- Mitochondrial DNA Mutation or Deletion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Minovia Therapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 1 Dec 2024 (actual)
- Study completion
- 1 Dec 2024 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 & Cohort 2 | Experimental | Procedure: Bone Marrow mobilization, Procedure: Apheresis, Biological: MNV-BM-PLC infusion3 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). |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bone Marrow mobilizationDuring 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 | Procedure or surgery | Cohort 1 & Cohort 2 |
| ApheresisApheresis will be performed two days prior to MNV-BM-PLC infusion. During this procedure, patient's peripheral blood will be collected by apheresis | Procedure or surgery | Cohort 1 & Cohort 2 |
| MNV-BM-PLC infusionThe 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. | Biological | Cohort 1 & Cohort 2 |
Primary outcome
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Time frame: 1 month
Severity will graded according to CTCAE, Version 5.0
Measurement of hemoglobin level
Time frame: 1 month
Change from baseline in hematological parameter
Measurement of absolute neutrophil count
Time frame: 1 month
Change from baseline in hematological parameter
Measurement of platelet count
Time frame: 1 month
Change from baseline in hematological parameter
10 secondary outcomes
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
Time frame: 2 years
Measurement of hemoglobin level
Time frame: 2 years
Measurement of absolute neutrophil count
Time frame: 2 years
Measurement of platelet count
Time frame: 2 years
IPMDS (International Pediatric Mitochondrial Disease Scale)
Time frame: 2 years
Performance Score
Time frame: 2 years
PEDI: Pediatric Evaluation of Disability Inventory
Time frame: 2 years
6-minute walk test
Time frame: 2 years
30 Second chair stand
Time frame: 2 years
Hospitalization events
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bone Marrow mobilization, Apheresis and MNV-BM-PLC infusion in people with Primary Mitochondrial Diseases, run by Minovia Therapeutics Ltd. at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC (time frame: 1 month). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.