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Active, not recruitingNCT03706482BOOSTB4Updated Sep 12, 2025

Boost Brittle Bones Before Birth

A Phase 1/2 interventional study of BOOST cells in Osteogenesis Imperfecta, sponsored by Karolinska Institutet. Active, not recruiting at 1 site in Sweden. Open to participants aged Up to 18 Months. Per ClinicalTrials.gov, last updated 2025-09-12.

Sponsored by Karolinska Institutet · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
18
Allocation
Non-randomized
Ages
Up to 18 Months
Sex
All
01

Study 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.

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Conditions studied

  • Osteogenesis Imperfecta
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Who can participate

Ages eligible
Up to 18 Months
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria Postnatal Group:

  1. Parent's/legal guardian's signed informed-consent form
  2. Clinical diagnosis of OI type III or severe type IV AND
  3. Molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
  4. Age less than 18 months (calculated from gestational week 40+0, i.e. the corrected age)
  5. Parent/legal guardian over 18 years of age

Inclusion Criteria Prenatal Group:

  1. Woman has signed the informed-consent form
  2. 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
  3. Suspicion of OI type III or severe type IV in the fetus on ultrasound findings AND
  4. Molecular diagnosis of OI in the fetus (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
  5. Gestation age between 16+0 and 35+6 weeks+days
  6. Pregnant woman over 18 years of age

Inclusion Criteria Historical Control Group:

  1. Parent's/legal guardian's signed informed-consent form
  2. Clinical and molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
  3. Data on fractures and growth is available
  4. Parent/legal guardian over 18 years of age

Inclusion Criteria Prospective Untreated Control Group:

  • Postnatal inclusion: The inclusion criteria for the postnatal group apply.
  • Prenatal inclusion: The inclusion criteria for the prenatal group apply, except inclusion criteria 2.

Exclusion Criteria Postnatal Group:

  1. 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.
  2. Any contraindication for invasive procedures such as a moderate/severe bleeding tendency
  3. 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)
  4. Positive Donor Specific Antibody-test
  5. Known allergy/hypersensitivity to Fungizone and/or Gensumycin
  6. Abnormal karyotype or other confirmed genetic syndromes
  7. Oncologic disease (previous or current malignancy)
  8. Inability to comply with the trial protocol and follow-up schedule
  9. Inability to understand the information and to provide informed consent

Exclusion Criteria Prenatal Group:

  1. Multiple pregnancy
  2. Co-existence of other disorder that might interfere with the treatment, as judged by the Investigator or the patient's obstetrician
  3. Abnormal fetal karyotype or other confirmed genetic syndrome
  4. 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
  5. 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)
  6. Positive Donor Specific Antibody-test
  7. Known allergy/hypersensitivity to Fungizone and/or Gensumycin
  8. Oncologic disease in woman or fetus (previous or current malignancy)
  9. Unwilling to or cannot undergo delivery by elective Caesarean section
  10. Inability to comply with the trial protocol and follow-up schedule
  11. Inability to understand the information and to provide informed consent

Exclusion Criteria Historical Control Group:

  1. Existence of other disorder that might interfere with the trial. No lung hypoplasia (type II OI).
  2. Abnormal karyotype

Exclusion Criteria Prospective Untreated Control Group:

  • Postnatal inclusion: The exclusion criteria, except exclusion criterium 2, 3, 4 and 5 (Contraindication for invasive procedure, Known risk factor for clotting, Positive Donor Specific Antibody-test and Known allergy/hypersensitivity to Fungizone and/or Gensumycin) for the postnatal group apply.
  • Prenatal inclusion: The exclusion criteria, except exclusion criterium 1, 4, 5, 6 and 7 (Multiple pregnancy, Contraindication for invasive procedure, Known risk factor for clotting, Positive Donor Specific Antibody-test and Known allergy/hypersensitivity to Fungizone and/or Gensumycin) for the prenatal group apply.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Postnatal

    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

  • Experimental
    Prenatal

    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

  • No intervention
    Prospective control (untreated)

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

  • No intervention
    Historic control

    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

  • BiologicalBOOST cells

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

05

What researchers measure

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

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

Secondary outcomes

  1. Number of fractures.

    Number of fractures.

    Time frame: 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).

  2. Time (days) to first fracture after each stem cell administration.

    Time (days) to first fracture after each stem cell administration.

    Time frame: 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.

  3. Numbers of fractures at birth.

    Numbers of fractures at birth.

    Time frame: Evaluated at birth.

  4. Change in bone-marrow density (g/cm2).

    Change in bone-marrow density (g/cm2).

    Time frame: 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).

  5. Growth (cm).

    Growth (cm) as assessed by clinician.

    Time frame: 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).

  6. Growth (kg).

    Growth (kg) as assessed by clinician.

    Time frame: 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).

  7. Change in clinical status of OI.

    Change in clinical status of OI based on parameters defined under efficacy assessments described in protocol, as assessed by OI clinician.

    Time frame: 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).

  8. 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.

    Assessment of biochemical bone turnover.

    Time frame: 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

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

    Quality of life assessed using the Infant Toddler Quality of Life Questionnaire™ (ITQOL).

    Time frame: 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).

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

    Donor cell engraftment.

    Time frame: 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).

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

    Paracrine effects will be analysed from plasma isolated from peripheral blood.

    Time frame: 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).

  4. Assess the potential of non-invasive methods of prenatal diagnosis for OI by genetic analysis of parent DNA.

    Non-invasive prenatal diagnosis will be studied during the trial.

    Time frame: From baseline to birth for prenatal group.

06

Study locations

1 site
  • Karolinska University Hospital
    Stockholm, Stockholm County 171 76, Sweden
07

References and documents

Publications

  • 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. PubMed 38834319 ↗

Individual participant data

Plan to share: Yes — Individual participant data that underlie the results reported in this trial, after deidentification (text, tables, figures, and appendices).

Supporting information: Study protocol, Icf, Csr

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Registry details

Key details

Study ID
NCT03706482
Lead sponsor
Karolinska Institutet
Collaborators
Karolinska University Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, University College, London, Universitätsklinikum Köln, UMC Utrecht, Leiden University Medical Center, Lund University
Responsible party
Cecilia Götherström (Sponsor's representative, Karolinska Institutet) — Principal investigator
First posted
Oct 16, 2018
Start date
Aug 12, 2019
Primary completion
Apr 2030 (estimated)
Completion
Apr 2030 (estimated)
Last update
Sep 12, 2025

Study contacts

Eva Åström, MD PhD
principal investigator · Karolinska University Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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