An Exploratory, Open Label, Multiple Dose, Multicentre Phase I/II Trial Evaluating Safety and Efficacy of Postnatal or Prenatal and Postnatal Intravenous Administration of Allogeneic Expanded Fetal Mesenchymal Stem Cells for the Treatment of Severe Osteogenesis Imperfecta Compared With a Combination of Historical and Untreated Prospective Controls
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events.
研究概览
简要总结
An exploratory, open label, multiple dose, multicentre phase I/II trial evaluating safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe Osteogenesis Imperfecta compared with a combination of historical and untreated prospective controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Postnatal
15 participants.
Administration of four postnatal doses of BOOST cells with the first dose as soon as possible after birth and the three additional doses at +4, +8 and +12 months after the first dose. Each dose is 3x10^6 MSC/kg body weight.
干预措施: BOOST cells (Biological)
Prenatal
3 participants.
Administration of one prenatal dose of BOOST cells followed by three postnatal doses at +4, +8 and +12 months after the first dose. Each dose is 3x10^6 MSC/kg body weight.
干预措施: BOOST cells (Biological)
结局指标
主要结局
Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events.
时间窗: From baseline to the long-time follow-up (10 years after the first dose).
The primary endpoint is safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs), with specific focus on the following: 1. Vital signs in conjunction with the MSC administration 2. Transfusion reactions (administration toxicity, allergy, embolism) 3. Immune reaction with or without symptoms of inflammation, potentially resulting in rejection of the cells or development of donor-specific antibodies: * Allergy or Hypersensitivity responses to antibiotics or antimycotics * Development of Fetal Bovine Serum-specific antibodies * Hypersensitivity responses to Human Serum Albumin * Hypersensitivity to impurities in the IMP 4. Prenatal complications (miscarriage/intrauterine fetal death, premature birth, infection in utero or persistent \[\>1 min\] fetal bradycardia) in the prenatal group 5. Adverse effects of feto-maternal transmission of donor cells in the prenatal group 6. Tumourigenicity 7. Mortality/morbidity
次要结局
- Number of fractures.(From baseline to the primary follow-up (6 and 12 months after the last dose) and therafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
- Change in bone-marrow density (g/cm2).(From baseline to the primary follow-up (6 and 12 months after the last dose) and thereafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
- Time (days) to first fracture after each stem cell administration.(From each dose of stem cells to the time point of the first fracture. Assessed up to 10 years after the first stem cell dose.)
- Numbers of fractures at birth.(Evaluated at birth.)
- Growth (kg).(From baseline to the primary follow-up (6 and 12 months after the last dose) and thereafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
- Growth (cm).(From baseline to the primary follow-up (6 and 12 months after the last dose) and thereafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
- Change in clinical status of OI.(From baseline to the primary follow-up (6 and 12 months after the last dose) and thereafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
- Assessment of biochemical bone turnover by analysis of the markers P-Calcium, P-Phosphate, P-Albumin, S-ALP, fP-PTH, S-25-OH Vitamin D, Bone specific S-ALP, S-CTx, S-Osteocalcin and U-DPD/Krea and U-NTx/Krea in blood and urine samples.(From baseline to the primary follow-up (6 and 12 months after the last dose) and thereafter assessed annually to the end of the long-time follow-up (10 years after the first dose).)
研究者
Cecilia Götherström
Sponsor's representative
Karolinska Institutet