Boost Brittle Bones Before Birth

NCT03706482 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: KIBB012015-003699-60
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteogenesis Imperfecta

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events.

  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

  From baseline to the long-time follow-up (10 years after the first dose).

Secondary Outcomes (8)

• 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).

• 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.

• 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).

• 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).

Other Outcomes (4)

• Impact on the subjects Quality of Life: Infant Toddler Quality of Life Questionnaire™ (ITQOL)

  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).

• Incidence of donor cells engrafted into patient tissue samples assessed by histology.

  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).

• Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects.

  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).

Study Arms (4)

Postnatal

EXPERIMENTAL

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.

Biological: BOOST cells

Prenatal

EXPERIMENTAL

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.

Biological: BOOST cells

Prospective control (untreated)

NO INTERVENTION

1-30 participants. Subjects eligible for the trial but not willing/able to participate in any of the experimental arms.

Historic control

NO INTERVENTION

18-90 participants (1-5 per included and treated subject). Matched historical controls. Subjects will be identified in historical registries and data will be retrieved from national OI registers and the OI Variant Database (Dalgleish 2018).

Interventions

BOOST cells BIOLOGICAL

Four doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells.

Postnatal; Prenatal

Eligibility Criteria

• Age: Up to 18 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent's/legal guardian's signed informed-consent form
• Clinical diagnosis of OI type III or severe type IV AND
• Molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
• Age less than 18 months (calculated from gestational week 40+0, i.e. the corrected age)
• Parent/legal guardian over 18 years of age
• Woman has signed the informed-consent form
• Only women where termination of the pregnancy is no longer possible or where the women are committed to continue the pregnancy may be included in the trial
• Suspicion of OI type III or severe type IV in the fetus on ultrasound findings AND
• Molecular diagnosis of OI in the fetus (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
• Gestation age between 16+0 and 35+6 weeks+days
• Pregnant woman over 18 years of age
• Parent's/legal guardian's signed informed-consent form
• Clinical and molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
• Data on fractures and growth is available
• Parent/legal guardian over 18 years of age

You may not qualify if:

• Existence of other known disorder that might interfere with the treatment, such as, but not limited to organ dysfunction (for example liver or renal failure or bronchopulmonary dysplasia), congenital heart defect, hypoxic encephalopathy l-lll, severe neurological problems, immune deficiencies, muscle diseases, severe malformations or syndromes diagnosed by clinical examination.
• Any contraindication for invasive procedures such as a moderate/severe bleeding tendency
• Known risk factors for clotting, such as, but not limited to previous blood clot, family history of clots, clotting disorder (inherited or acquired), heart failure, inflammatory disorders (for example lupus, rheumatoid arthritis, inflammatory bowel disease)
• Positive Donor Specific Antibody-test
• Known allergy/hypersensitivity to Fungizone and/or Gensumycin
• Abnormal karyotype or other confirmed genetic syndromes
• Oncologic disease (previous or current malignancy)
• Inability to comply with the trial protocol and follow-up schedule
• Inability to understand the information and to provide informed consent
• Multiple pregnancy
• Co-existence of other disorder that might interfere with the treatment, as judged by the Investigator or the patient's obstetrician
• Abnormal fetal karyotype or other confirmed genetic syndrome
• Any contraindication for invasive procedures such as a bleeding tendency or contagious infections, such as, but not limited to HIV, Syphilis, Hepatitis B, Hepatitis C or other known infectious diseases that can harm the fetus
• Known risk factors for clotting, such as, but not limited to previous blood clot, family history of clots, clotting disorder (inherited or acquired), heart failure, inflammatory disorders (for example lupus, rheumatoid arthritis, inflammatory bowel disease)
• Positive Donor Specific Antibody-test

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• University College, London: collaborator
• Universitätsklinikum Köln: collaborator
• UMC Utrecht: collaborator
• Leiden University Medical Center: collaborator
• Lund University: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, Stockholm County, 171 76, Sweden

Location

Related Publications (1)

• Sagar RL, Astrom E, Chitty LS, Crowe B, David AL, DeVile C, Forsmark A, Franzen V, Hermeren G, Hill M, Johansson M, Lindemans C, Lindgren P, Nijhuis W, Oepkes D, Rehberg M, Sahlin NE, Sakkers R, Semler O, Sundin M, Walther-Jallow L, Verweij EJTJ, Westgren M, Gotherstrom C. 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. 2024 Jun 4;14(6):e079767. doi: 10.1136/bmjopen-2023-079767.

  PMID: 38834319 DERIVED

MeSH Terms

Conditions

Osteogenesis Imperfecta

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Eva Åström, MD PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor's representative

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 16, 2018
• Study Start: August 12, 2019
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent ethics review committee can submit proposals up to 36 months following article publication. After 36 months the data will be available in our Institute's data warehouse but without investigator support other than deposited metadata. Since the IPD is coded and a code key exists, study participants can be identified indirectly via the code key and the IPD is classified as personal data according to the GDPR General Data Protection Regulation (Regulation (EU) 2016/679). Data requestors will need to adhere to GDPR and sign a data transfer agreement. Data requestors from non-EU/EES countries will also need to sign the EU commissions Standard Contractual Clauses for data transfer between EU and non-EU countries. Proposals should be directed to boostb4@clintec.ki.se.

Locations

SE (1)