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
Anna L David,
Mats Johansson,
Magnus Westgren,
Belinda Crowe,
Dick Oepkes,
Melissa Hill,
Lyn S Chitty,
Catherine DeVile,
Peter Lindgren,
Eva Åström,
Cecilia Götherström,
Nils-Eric Sahlin,
Rachel L Sagar,
Annabelle Forsmark,
Vera Franzen,
Göran Hermeren,
Caroline Lindemans,
Wouter Nijhuis,
Mirko Rehberg,
Ralph Sakkers,
O Semler,
Mikael Sundin,
Lilian Walther-Jallow,
E J T Joanne Verweij
Affiliations
Anna L David
2 NIHR University College London Hospitals Biomedical Research Centre, London, UK
Mats Johansson
10 Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
Magnus Westgren
13 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Belinda Crowe
7 Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Dick Oepkes
15 Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
Melissa Hill
5 North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Lyn S Chitty
5 North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Catherine DeVile
7 Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Peter Lindgren
12 Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
Eva Åström
3 Department of Women’s and Children`s Health, Karolinska Institutet, Stockholm, Sweden
Cecilia Götherström
13 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Nils-Eric Sahlin
10 Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
Rachel L Sagar
1 Elizabeth Garrett Anderson Institute for Women`s Health, University College London, London, UK
Annabelle Forsmark
8 PharmaLex, Gothenburg, Sweden
Vera Franzen
9 XNK Therapeutics AB, Huddinge, Sweden
Göran Hermeren
10 Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden
Caroline Lindemans
11 Department of Pediatrics, University Medical Centre Utrecht, Utrecht, The Netherlands
Wouter Nijhuis
14 Department of Orthopedic Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
Mirko Rehberg
16 Department of Pediatrics, University Hospital Cologne, Koln, Nordrhein-Westfalen, Germany
Ralph Sakkers
14 Department of Orthopedic Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
O Semler
16 Department of Pediatrics, University Hospital Cologne, Koln, Nordrhein-Westfalen, Germany
Mikael Sundin
13 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Lilian Walther-Jallow
13 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
E J T Joanne Verweij
15 Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
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 3×106/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.
