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
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
Cohort 1 & Cohort 2
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).
干预措施: Bone Marrow mobilization (Procedure)
Cohort 1 & Cohort 2
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).
干预措施: Apheresis (Procedure)
Cohort 1 & Cohort 2
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).
干预措施: MNV-BM-PLC infusion (Biological)
结局指标
主要结局
Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC
时间窗: 1 month
Severity will graded according to CTCAE, Version 5.0
Measurement of platelet count
时间窗: 1 month
Change from baseline in hematological parameter
Measurement of hemoglobin level
时间窗: 1 month
Change from baseline in hematological parameter
Measurement of absolute neutrophil count
时间窗: 1 month
Change from baseline in hematological parameter
次要结局
- Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-PLC(2 years)
- Measurement of hemoglobin level(2 years)
- Measurement of absolute neutrophil count(2 years)
- Measurement of platelet count(2 years)
- IPMDS (International Pediatric Mitochondrial Disease Scale)(2 years)
- Performance Score(2 years)
- PEDI: Pediatric Evaluation of Disability Inventory(2 years)
- 6-minute walk test(2 years)
- 30 Second chair stand(2 years)
- Hospitalization events(1 year)