Boost Brittle Bones Before Birth

NCT ID: NCT03706482

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-12
• Study Completion Date: 2030-04-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

BOOST cells

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

BOOST cells

Intervention Type: BIOLOGICAL

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

Prospective control (untreated)

1-30 participants.

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

BOOST cells

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

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

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

Exclusion Criteria

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

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

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

2. Abnormal karyotype

• Maximum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

Universitätsklinikum Köln

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Lund University

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Cecilia Götherström

Sponsor's representative

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eva Åström, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Karolinska University Hospital

Stockholm, Stockholm County, Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 38834319 (View on PubMed)

Other Identifiers

2015-003699-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KIBB01

Identifier Type: -

Identifier Source: org_study_id