Osteogenesis ImperfectaPhase 1/2BOOSTB4NCT03706482
Boost Brittle Bones Before Birth
A Phase 1/2 study testing BOOST cells in people with Osteogenesis Imperfecta, run by Karolinska Institutet at 1 site in Sweden.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 18 months
- Conditions the study is for
- Osteogenesis Imperfecta
- What is being tested?
- BOOST cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSweden
- Study dates
- 12 Aug 2019to Apr 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
- Postnatal inclusion: The inclusion criteria for the postnatal group apply.
- Prenatal inclusion: The inclusion criteria for the prenatal group apply, except inclusion criteria 2.
Who cannot join
- 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
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- 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
- Known allergy/hypersensitivity to Fungizone and/or Gensumycin
- Oncologic disease in woman or fetus (previous or current malignancy)
- Unwilling to or cannot undergo delivery by elective Caesarean section
- Inability to comply with the trial protocol and follow-up schedule
- Inability to understand the information and to provide informed consent
- Existence of other disorder that might interfere with the trial. No lung hypoplasia (type II OI).
- Abnormal karyotype
- 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.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Karolinska University Hospital
Stockholm, Stockholm County, 171 76
About this study
Official title: An Exploratory, Open Label, Multiple Dose, Multicentre Phase I/II Trial Evaluating Safety and Efficacy of Postnatal or Prenatal and Postnatal Intravenous 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
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
- Being tested
- BOOST cells
- Medical subject headings
- Osteogenesis Imperfecta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BOOST cellsBiological
Four doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Vital signs in conjunction with the MSC administration
- Transfusion reactions (administration toxicity, allergy, embolism)
- 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
- Prenatal complications (miscarriage/intrauterine fetal death, premature birth, infection in utero or persistent [>1 min] fetal bradycardia) in the prenatal group
- Adverse effects of feto-maternal transmission of donor cells in the prenatal group
- Tumourigenicity
- Mortality/morbidity
Measured: From baseline to the long-time follow-up (10 years after the first dose).
Secondary outcomes (8)
Number of fractures.
Number of fractures.
Measured: 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.
Time (days) to first fracture after each stem cell administration.
Measured: 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.
Numbers of fractures at birth.
Measured: Evaluated at birth.
Change in bone-marrow density (g/cm2).
Change in bone-marrow density (g/cm2).
Measured: 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).
Growth (cm) as assessed by clinician.
Measured: 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 (kg).
Growth (kg) as assessed by clinician.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start12 Aug 2019
- Primary completionApr 2030 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteogenesis ImperfectaStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- 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
- Principal investigator, Cecilia Götherström, Karolinska Institutet
- Investigators
- Eva Åström, MD PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03706482
- Sponsor's protocol ID
- KIBB01
- Other IDs
- 2015-003699-60, 2015
- Acronym
- BOOSTB4
- Status last verified
- Sep 2025
- First submitted
- 5 Oct 2018
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this trial, after deidentification (text, tables, figures, and appendices).
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
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Open Label, Multiple Dose, Multicentre Phase I/II Trial Evaluating Safety and Efficacy of Postnatal or Prenatal and Postnatal Intravenous 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
- ClinicalTrials.gov ID
- NCT03706482
- Acronym / sponsor ID
- BOOSTB4 / KIBB01
- Conditions
- Osteogenesis Imperfecta
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- 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
- Study start
- 12 Aug 2019 (actual)
- Primary completion
- Apr 2030 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 16 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Postnatal | Experimental | Biological: BOOST cells15 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. |
| Prenatal | Experimental | Biological: BOOST cells3 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. |
| 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). |
Who may qualify
- Ages
- Up to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BOOST cellsFour doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells. | Biological | Postnatal, Prenatal |
Primary outcome
Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events.
Time frame: From baseline to the long-time follow-up (10 years after the first dose).
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
8 secondary outcomes
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).
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.
Numbers of fractures at birth.
Time frame: Evaluated at birth.
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).
Growth (cm).
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).
Growth (kg).
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).
Change in clinical status of OI.
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).
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.
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Derived from this study: PubMed 38834319Sagar 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.
- BOOSTB4 consortium web siteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this trial, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Åström, MD PhD principal investigator
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BOOST cells in people with Osteogenesis Imperfecta, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events. (time frame: From baseline to the long-time follow-up (10 years after the first dose).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03706482, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.