An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol
BMJ Open, vol. 14, pp. e079767
Abstract
Introduction Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. Methods and analysis BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1–5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial. Each subject receives four intravenous doses of 3×10 6 /kg BOOST cells at 4 month intervals, with 48 (doses 1–2) or 24 (doses 3–4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally. The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. Ethics and dissemination The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. Trial registration numbers EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482 .
Authors 23
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
Department of Women’s and Children's Health, Karolinska Institutet, Stockholm, Sweden
Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
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Great Ormond Street Hospital · Great Ormond Street Hospital for Children NHS Foundation Trust · University College London
Affiliation as printed
Genetics and Genomics, UCL Great Ormond Street Institute of Child Health, London, UK
North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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Great Ormond Street Hospital · Great Ormond Street Hospital for Children NHS Foundation Trust
Affiliation as printed
Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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UCL Biomedical Research Centre · University College London
Affiliation as printed
Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK
NIHR University College London Hospitals Biomedical Research Centre, London, UK
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Great Ormond Street Hospital · Great Ormond Street Hospital for Children NHS Foundation Trust
Affiliation as printed
Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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Affiliation as printed
PharmaLex, Gothenburg, Sweden
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Affiliation as printed
XNK Therapeutics AB, Huddinge, Sweden
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Affiliation as printed
Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
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Great Ormond Street Hospital · Great Ormond Street Hospital for Children NHS Foundation Trust · University College London
Affiliation as printed
Genetics and Genomics, UCL Great Ormond Street Institute of Child Health, London, UK
North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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Affiliation as printed
Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
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University Medical Center Utrecht
Affiliation as printed
Department of Pediatrics, University Medical Centre Utrecht, Utrecht, The Netherlands
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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University Medical Center Utrecht
Affiliation as printed
Department of Orthopedic Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Pediatrics, University Hospital Cologne, Koln, Nordrhein-Westfalen, Germany
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Affiliation as printed
Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
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University Medical Center Utrecht
Affiliation as printed
Department of Orthopedic Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
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Affiliation as printed
Department of Pediatrics, University Hospital Cologne, Koln, Nordrhein-Westfalen, Germany
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Section of Pediatic Hematology, Immunology and HCT, Karolinska University Hospital, Stockholm, Sweden
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Affiliation as printed
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Leiden University Medical Center
Affiliation as printed
Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Cecilia on the Gotherstrom corresponding
Affiliation as printed
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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