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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

Sagar, Rachel L ; Åström, Eva ; Chitty, Lyn S ; Crowe, Belinda ; David, Anna L ; DeVile, Catherine ; Forsmark, Annabelle ; Franzen, Vera ; Hermerén, Göran LU and Hill, Melissa , et al. (2024) In BMJ Open 14(6).
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMJ Open
volume
14
issue
6
article number
e079767
publisher
BMJ Publishing Group
external identifiers
  • pmid:38834319
  • scopus:85195250208
ISSN
2044-6055
DOI
10.1136/bmjopen-2023-079767
language
English
LU publication?
yes
id
d491b132-d3ed-4684-b038-89116f8e2ab9
date added to LUP
2024-06-11 11:28:15
date last changed
2024-06-12 04:00:41
@article{d491b132-d3ed-4684-b038-89116f8e2ab9,
  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.<br/><br/>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&lt;18 months of age (originally&lt;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.<br/><br/>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.<br/><br/>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.<br/><br/>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.<br/><br/>Trial registration numbers EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.}},
  author       = {{Sagar, Rachel L and Åström, Eva and Chitty, Lyn S and Crowe, Belinda and David, Anna L and DeVile, Catherine and Forsmark, Annabelle and Franzen, Vera and Hermerén, Göran and Hill, Melissa and Johansson, Mats and Lindemans, Caroline and Lindgren, Peter and Nijhuis, Wouter and Oepkes, Dick and Rehberg, Mirko and Sahlin, Nils-Eric and Sakkers, Ralph and Semler, O and Sundin, Mikael and Walther-Jallow, Lilian and Verweij, EJT Joanne and Westergren, Magnus and Götherström, Cecilia}},
  issn         = {{2044-6055}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{BMJ Open}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1136/bmjopen-2023-079767}},
  doi          = {{10.1136/bmjopen-2023-079767}},
  volume       = {{14}},
  year         = {{2024}},
}