Osteogenesis ImperfectaPhase 3CosmicNCT05768854
Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
A Phase 3 study testing Bisphosphonate and Setrusumab in people with Osteogenesis Imperfecta, run by Ultragenyx Pharmaceutical Inc at 20 sites in 7 countries.
Trial summary
The primary objective of the study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants. Read more about this study
- Who is it for?
- Ages 2 to 6 years
- Conditions the study is for
- Osteogenesis Imperfecta
- What is being tested?
- Bisphosphonate and Setrusumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 14 Jun 2023to Apr 2027
- Phase
- Phase 3
- 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 2 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female 2 to < 7 years of age at time of informed consent
- Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2
- History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months
- Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI
- Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after a minimum of 14 days of vitamin D supplementation as directed by the Investigator
Who cannot join
- Contraindication for the use of IV bisphosphonates based on clinical judgment of the Investigator
- History of skeletal malignancies or bone metastases at any time
- History of neural foraminal stenosis (except if due to scoliosis)
- Clinical manifestations of Chiari malformation or basilar invagination. Presence of any other neurologic disease that has been clinically unstable within past 2 years requires review by the Medical Monitor.
- History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease
- Any skeletal condition (other than OI) leading to bone deformity and/or increased risk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis, or skeletal dysplasia
Show all 15Show fewer
- History of known cardiovascular disease such as coronary artery anomaly, Kawasaki disease, myocarditis, cardiomyopathy, myocardial infarction, stroke, or thromboembolic disease. Individuals with other congenital or acquired cardiovascular disease necessitating echocardiogram require Medical Monitor review. Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with cardiovascular risk factors such as confirmed arterial hypertension.
- Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limit reference ranges after a recommended ≥ 4 hour fast, at Screening
- Estimated glomerular filtration rate <=35 mL/min/1.73 m2 at Screening
- Prior treatment with growth hormone, denosumab, anti-sclerostin antibody, or other anabolic or anti-resorptive medications impacting the bone (other than bisphosphonates) at any time
- History of external radiation therapy
- Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
- Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
- Use of any investigational product or investigational medical device within 4 weeks or 5 half-lives (whichever is longer) of investigational drug prior to Screening, or during the study (per discretion of the Investigator in consultation with the Medical Monitor)
- Concurrent participation in another clinical study without prior approval from the study Medical Monitor
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
United States13 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
University of North Carolina at Chapel Hill (UNC)
Chapel Hill, North Carolina, 27599
Shriners Hospitals for Children Chicago
Chicago, Illinois, 60707
Cook Children's Medical Center
Fort Worth, Texas, 76104
Baylor College of Medicine
Houston, Texas, 77030
Childrens Hospital LA
Los Angeles, California, 90027
Vanderbilt University Medical Center (VUMC)
Nashville, Tennessee, 37212
Yale New Haven Hospital
New Haven, Connecticut, 06510
Phoenix Children's Hospital
Phoenix, Arizona, 85206
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Children's National Hospital DC
Washington D.C., District of Columbia, 20010
Nemours/ Alfred i. duPoint Hospital for Children
Wilmington, Delaware, 19803
Canada2 sites
Children's Hospital at London Health Sciences Centre
London, Ontario, N6A 5W9
Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa
Ottawa, KIH 8L1
Brazil1 site
Hospital de Clinicas de Porto Alegre (HCPA)
Porto Alegre, Rio Grande do Sul, 90035-903
Netherlands1 site
Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis
Utrecht, 3584 EA
Poland1 site
Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych
Lodz, 91-738
About this study
Official title: An Open-label, Randomized, Active-Controlled, Phase 3 Study of Setrusumab Compared With Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta Types I, III or IV
The primary objective of the study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants.
Read the detailed description
Participants will be randomized 1:1 to receive either setrusumab or IV-BP. Following randomization, participants will receive setrusumab or IV-BP for up to 24 months during the Active-controlled Period. At the end of the Active-controlled Period all participants will enter the Extension Period and participants assigned to IV-BP will transition to setrusumab. During the Extension Period, all participants will receive setrusumab for a minimum of 12 months or until setrusumab becomes commercially available in their respective country or the study is discontinued. The use of any bisphosphonate is prohibited throughout the Extension Period.
- Conditions
- Osteogenesis Imperfecta
- Being tested
- Bisphosphonate, Setrusumab
- Medical subject headings
- Osteogenesis Imperfecta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BisphosphonateDrug
Administered per investigator discretion via intravenous (IV) infusion
SetrusumabBiological
Also called BPS804, UX143
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Bisphosphonates (IV-BP) -> Setrusumab | Active comparator | Participants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator.
After the active-controlled period, participants will receive Setrusumab during the extension period Receives: Drug: Bisphosphonate; Biological: Setrusumab |
| Setrusumab | Experimental | Participants will receive Setrusumab during the active-controlled and extension period Receives: Biological: Setrusumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Rate of All Radiographically-Confirmed Fractures, Including Morphometric Vertebral Fractures, at the Primary Analysis
Measured: Up to 24 Months
Secondary outcomes (9)
Annualized Rate of Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, but Including Fractures of the Fingers, Toes, Face and Skull at the Primary Analysis
Measured: Up to 24 Months
Annualized Rate of All Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, and Fractures of the Fingers, Toes, Face and Skull, at the Primary Analysis
Measured: Up to 24 Months
Change from Baseline in Dual-energy X-ray Absorptiometry (DXA) Bone Mineral Density (BMD) Z-score at the Lumbar Spine at the Primary Analysis
Measured: Up to 24 Months
Proportion of Participants Experiencing New Radiographically-Confirmed Fractures, including Morphometric Vertebral Fractures, at the Primary Analysis
Measured: Up to 24 Months
Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning and Pain/Comfort Subscale Scores at the Primary Analysis
Measured: Baseline, Up to 24 Months
Percent Change from Baseline in DXA BMD at the Lumbar Spine at the Primary Analysis
Measured: Up to 24 Months
Serum Setrusumab Concentration
Measured: Up to 24 Months
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Measured: Up to 24 Months
Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
Measured: Up to 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2023
- Study start14 Jun 2023
- Primary completion23 Oct 2025
- Study completionApr 2027 (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 Ultragenyx Pharmaceutical IncThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05768854
- Sponsor's protocol ID
- UX143-CL314
- Other IDs
- 2023-504196-24-00, 2023
- Acronym
- Cosmic
- Status last verified
- Oct 2026
- First submitted
- 3 Mar 2023
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bartosik M, Windels O, von Brackel FN, Amling M, Oheim R. Romosozumab in postmenopausal women with classical Osteogenesis imperfecta. Arch Osteoporos. 2026 Jul 18;21(1):100. doi: 10.1007/s11657-026-01744-3.
PubMed 42470570
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Active-Controlled, Phase 3 Study of Setrusumab Compared With Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta Types I, III or IV
- ClinicalTrials.gov ID
- NCT05768854
- Acronym / sponsor ID
- Cosmic / UX143-CL314
- Conditions
- Osteogenesis Imperfecta
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2023 (actual)
- Primary completion
- 23 Oct 2025 (actual)
- Study completion
- Apr 2027 (estimated)
- First posted
- 14 Mar 2023 (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.
The primary objective of the study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants.
Detailed description
Participants will be randomized 1:1 to receive either setrusumab or IV-BP. Following randomization, participants will receive setrusumab or IV-BP for up to 24 months during the Active-controlled Period. At the end of the Active-controlled Period all participants will enter the Extension Period and participants assigned to IV-BP will transition to setrusumab. During the Extension Period, all participants will receive setrusumab for a minimum of 12 months or until setrusumab becomes commercially available in their respective country or the study is discontinued. The use of any bisphosphonate is prohibited throughout the Extension Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Bisphosphonates (IV-BP) -> Setrusumab | Active comparator | Drug: Bisphosphonate, Biological: SetrusumabParticipants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator. After the active-controlled period, participants will receive Setrusumab during the extension period |
| Setrusumab | Experimental | Biological: SetrusumabParticipants will receive Setrusumab during the active-controlled and extension period |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Male or female 2 to < 7 years of age at time of informed consent
- Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2
- History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months
- Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI
- Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after a minimum of 14 days of vitamin D supplementation as directed by the Investigator
Key exclusion criteria (15 listed)
- Contraindication for the use of IV bisphosphonates based on clinical judgment of the Investigator
- History of skeletal malignancies or bone metastases at any time
- History of neural foraminal stenosis (except if due to scoliosis)
- Clinical manifestations of Chiari malformation or basilar invagination. Presence of any other neurologic disease that has been clinically unstable within past 2 years requires review by the Medical Monitor.
- History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease
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 |
|---|---|---|
| BisphosphonateAdministered per investigator discretion via intravenous (IV) infusion | Drug | Intravenous Bisphosphonates (IV-BP) -> Setrusumab |
| SetrusumabAlso: BPS804, UX143A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion | Biological | Intravenous Bisphosphonates (IV-BP) -> Setrusumab, Setrusumab |
Primary outcome
Annualized Rate of All Radiographically-Confirmed Fractures, Including Morphometric Vertebral Fractures, at the Primary Analysis
Time frame: Up to 24 Months
9 secondary outcomes
Annualized Rate of Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, but Including Fractures of the Fingers, Toes, Face and Skull at the Primary Analysis
Time frame: Up to 24 Months
Annualized Rate of All Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, and Fractures of the Fingers, Toes, Face and Skull, at the Primary Analysis
Time frame: Up to 24 Months
Change from Baseline in Dual-energy X-ray Absorptiometry (DXA) Bone Mineral Density (BMD) Z-score at the Lumbar Spine at the Primary Analysis
Time frame: Up to 24 Months
Proportion of Participants Experiencing New Radiographically-Confirmed Fractures, including Morphometric Vertebral Fractures, at the Primary Analysis
Time frame: Up to 24 Months
Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning and Pain/Comfort Subscale Scores at the Primary Analysis
Time frame: Baseline, Up to 24 Months
Percent Change from Baseline in DXA BMD at the Lumbar Spine at the Primary Analysis
Time frame: Up to 24 Months
Serum Setrusumab Concentration
Time frame: Up to 24 Months
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Time frame: Up to 24 Months
Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
Time frame: Up to 24 Months
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 20 Oct 2026.
- Derived from this study: PubMed 42470570Bartosik M, Windels O, von Brackel FN, Amling M, Oheim R. Romosozumab in postmenopausal women with classical Osteogenesis imperfecta. Arch Osteoporos. 2026 Jul 18;21(1):100. doi: 10.1007/s11657-026-01744-3.
- Ultragenyx Osteogenesis Imperfecta (OI) Research StudyLink provided by the sponsor.
- Ultragenyx Transparency CommitmentLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Medical Director study director
Ultragenyx Pharmaceutical Inc
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bisphosphonate and Setrusumab in people with Osteogenesis Imperfecta, run by Ultragenyx Pharmaceutical Inc at 20 sites in 7 countries.
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 5 inclusion and 15 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 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, Brazil, France, Italy and 2 more countries. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Annualized Rate of All Radiographically-Confirmed Fractures, Including Morphometric Vertebral Fractures, at the Primary Analysis (time frame: Up to 24 Months). 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 NCT05768854, 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 20 Oct 2026.