Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruitment ended
Participants planned
138
Countries
2
Sites
3
Osteogenesis Imperfecta (OI) type III and severe type IV. Severe type of congenital Brittle bone disease.
The primary objective is to assess safety and tolerability in the child, fetus and woman after postnatal or prenatal and postnatal intravenous administration of four doses of BOOST cells in individuals with OI type III or severe type IV.
Key facts
- Sponsor
- Karolinska Institutet
- Participant type
- Pediatric, Patients
- Age range
- In Utero, 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 12 Aug 2019 → ongoing
- Decision date (initial)
- 2024-09-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- European Commission · Swedish Research Council
External identifiers
- EU CT number
- 2023-504593-38-00
- EudraCT number
- 2015-003699-60
- ClinicalTrials.gov
- NCT03706482
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The primary objective is to assess safety and tolerability in the child, fetus and woman after postnatal or prenatal and postnatal intravenous administration of four doses of BOOST cells in individuals with OI type III or severe type IV.
Secondary objectives 7
- Fracture frequency
- Time (days) to first fracture after last dose
- Number of fractures at birth (prenatal treatment group only)
- Bone mineral density
- Growth (cm and kg)
- Clinical status of OI
- Biochemical bone turnover
Conditions and MedDRA coding
Osteogenesis Imperfecta (OI) type III and severe type IV. Severe type of congenital Brittle bone disease.
Regulatory references
- Scientific advice from competent authorities
- Swedish Medical Products Agency, Swedish Medical Products Agency, European Medical Contract Manufacturing (E.M.C.M.) B.V.
- Plan to share IPD
- No
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Parent's/legal guardian's signed informed-consent form.
- Clinical diagnosis of OI type III or IV AND
- Molecular diagnosis of OI (Glycine substitution in the collagen triplehelix 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
Exclusion criteria 9
- Existence of other known disorder that might interfere with the treatment, such as, but not limited to organ dysfunction (for e.g. 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 e.g. 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoints are seriousness, severity and frequency of treatment-related AEs.)
Secondary endpoints 7
- Number of fractures from baseline to primary and long-time follow-up (key secondary endpoint)
- Time (days) to first fracture after last dose
- Number of fractures at birth (prenatal treatment group, and postnatal treatment group when available)
- Change in Bone mineral density (g/cm2) (supportive for the endpoint fracture frequency)
- Growth (cm and kg)
- Change in clinical status of OI based on parameters defined under efficacy assessments
- Change in biochemical bone turnover
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD11325601 · Product
- Active substance
- Allogeneic Fetal Mesenchymal Stem Cells
- Other product name
- BOOST cells (cryopreserved expanded human first-trimester fetal liver-derived mesenchymal stem cells)
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Not Authorised
- MA holder
- KAROLINSKA INSTITUTET
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/0000061939
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska Institutet
- Sponsor organisation
- Karolinska Institutet
- Address
- Nobels Vag 6
- City
- Solna
- Postcode
- 171 65
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska Institutet
- Contact name
- Cecilia Götherström
Public contact point
- Organisation
- Karolinska Institutet
- Contact name
- Cecilia Götherström
Locations
2 EU/EEA countries · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 8 | 2 |
| Sweden | Ongoing, recruitment ended | 130 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2021-02-26 | 2021-03-29 | 2023-12-31 | ||
| Sweden | 2019-08-12 | 2020-03-17 | 2023-12-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 20 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol 2023-504593-38-00 | 3.8 |
| Recruitment arrangements (for publication) | Recruitment Arrangements | 1 |
| Recruitment arrangements (for publication) | Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | BOOSTB4 Barndagbok_Swedish_v1_1_19-09-2018 | 1 |
| Subject information and informed consent form (for publication) | SIS and ICF donation | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF historical controls | 2.4 |
| Subject information and informed consent form (for publication) | SIS and ICF historisk kontroll | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF intervju | 1.2 |
| Subject information and informed consent form (for publication) | SIS and ICF intervju avbojt | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF postnatal | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF postnatal prospektiv kontroll | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF postnatal screening | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal bekraftelse | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal missfall avbruten | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal prospektiv kontroll | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal screening | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prenatal screening pappa | 1.1 |
| Subject information and informed consent form (for publication) | SIS and ICF prospective controls | 2.4 |
| Summary of Product Characteristics (SmPC) (for publication) | Summary of product characteristics_SmPC | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-31 | Sweden | Acceptable with conditions 2024-08-29
|
2024-08-29 |