Boost Brittle Bones Before Birth
- Conditions
- Osteogenesis Imperfecta
- Interventions
- Biological: BOOST cells
- Registration Number
- NCT03706482
- Lead Sponsor
- Karolinska Institutet
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Postnatal BOOST cells 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. Prenatal BOOST cells 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.
- Primary Outcome Measures
Name Time Method Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events. 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
- Secondary Outcome Measures
Name Time Method 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). Number of fractures.
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). Change in bone-marrow density (g/cm2).
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. Time (days) to first fracture after each stem cell administration.
Numbers of fractures at birth. Evaluated at birth. Numbers of fractures 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 (kg) as assessed by clinician.
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). Growth (cm) as assessed by clinician.
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). Change in clinical status of OI based on parameters defined under efficacy assessments described in protocol, as assessed by OI clinician.
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). Assessment of biochemical bone turnover.
Trial Locations
- Locations (1)
Karolinska University Hospital
đŸ‡¸đŸ‡ªStockholm, Sweden