Setrusumab vs Placebo for Osteogenesis Imperfecta
Orbit
An Operationally Seamless, Randomized Phase 2/3 Study Consisting of a Phase 2 Single-Blind, Dose-Evaluation Phase and a Phase 3 Double-Blind, Placebo-Controlled Phase to Assess the Efficacy and Safety of Setrusumab in Subjects With Osteogenesis Imperfecta
3 other identifiers
interventional
183
11 countries
44
Brief Summary
The primary objectives of the study are to identify a setrusumab dosing strategy in participants with OI and to evaluate the effect of setrusumab vs placebo on reduction in fracture rate.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2022
Longer than P75 for phase_2
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 8, 2021
CompletedFirst Posted
Study publicly available on registry
November 18, 2021
CompletedStudy Start
First participant enrolled
February 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 20, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2027
ExpectedFebruary 25, 2026
February 1, 2026
3.7 years
November 8, 2021
February 24, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Phase 2: Percent Change in Serum Amino-terminal Propeptide of Type 1 Procollagen (P1NP) from Baseline at Month 1
Baseline, Month 1
Phase 3: Annualized Rate of All Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures and Fractures of the Fingers, Toes, Face, and Skull at the Primary Analysis
Up to Month 24
Secondary Outcomes (18)
Phase 2: Serum Setrusumab Concentration
From Predose up to Month 24
Phase 2: Baseline-Corrected Area Under the Effect Curve (AUEC) for Serum P1NP Over a 1 and 2-Month Period
Baseline, Up to Month 2
Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: P1NP
Baseline, Up to Month 24
Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Osteocalcin (OCN)
Baseline, Up to Month 24
Phase 2: Change from Baseline in Dual Energy X-ray (DXA) Lumbar Spine Bone Mineral Density (BMD) Z-score Over Time
Baseline, Up to Month 24
- +13 more secondary outcomes
Study Arms (4)
Low Dose Setrusumab -> Open-Label (OL) Setrusumab Selected Dose
EXPERIMENTALSingle-blind setrusumab low dose during Phase 2 followed by open-label setrusumab selected dose During treatment and treatment extension periods, participants may receive supplementation with calcium and vitamin D to maintain normal values as directed by the treating physician
High Dose Setrusumab -> OL Setrusumab Selected Dose
EXPERIMENTALSingle-blind setrusumab high dose during Phase 2 followed by open-label setrusumab During treatment and treatment extension periods, participants may receive supplementation with calcium and vitamin D to maintain normal values as directed by the treating physician
Setrusumab Selected Dose -> OL Setrusumab Selected Dose
EXPERIMENTALDouble-blind setrusumab selected dose during Phase 3 followed by open-label setrusumab During treatment and treatment extension periods, participants may receive supplementation with calcium and vitamin D to maintain normal values as directed by the treating physician
Placebo -> OL Setrusumab Selected Dose
PLACEBO COMPARATORDouble-blind placebo during Phase 3 followed by open-label setrusumab During treatment and treatment extension periods, participants may receive supplementation with calcium and vitamin D to maintain normal values as directed by the treating physician
Interventions
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
A 5% dextrose/glucose solution administered QM via IV infusion
Eligibility Criteria
You may qualify if:
- Diagnosis of OI Type I, III, or IV as confirmed by identification of pathogenic or likely pathogenic genetic variants in COL1A1 or COL1A2. If a variant of uncertain significance is identified, then clinical presence of the expected phenotype can be used to confirm the diagnosis
- ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months or ≥ 1 tibia, femur or humerus fracture in the past 24 months
- Serum 25-hydroxyvitamin D ≥ 20 ng/mL at the Screening Visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, 25-hydroxyvitamin D testing can repeated after a minimum of 14 days of vitamin D supplementation as directed by the treating physician
- Willing to not receive bisphosphonate therapy during the study
- From the period following informed consent to 60 days after the last dose of the study drug, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not to father a child or donate sperm
- Willing and able to provide informed consent for subjects greater than or equal to 18 years of age, or provide assent (if possible) and have a legally authorized representative provide informed consent, after the nature of the study has been explained and prior to any research-related procedures
- Willing to provide access to medical records for the collection of radiographic data, fracture data, growth data, and disease history
- Must, in the opinion of the Investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with the assessments
You may not qualify if:
- 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 unstable within past 2 years requires review by the Medical Monitor
- History of or uncontrolled concomitant diseases such as hypo/hyperparathyroidism, Paget's disease, abnormal thyroid function, thyroid disease or other endocrine disorders or conditions that could affect bone metabolism such as Stage IV/V renal disease
- Rickets or any skeletal condition (other than OI) leading to long-bone deformities and/or increased risk of fractures
- History of stroke, myocardial infarction, transient ischemic attack or angina.
- Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limits after a ≥ 4 hour fast
- Estimated glomerular filtration rate ≤ 29 mL/min/1.73 m2
- Prior treatment with the following:
- Teriparatide, growth hormone, bone anabolic, or anti-resorptive medications (other than bisphosphonates) within 6 months of the first dose with study drug (Month 0)
- Denosumab within 24 months of Screening
- Romosozumab at any time
- Documented alcohol and/or drug abuse within 12 months prior to dosing or evidence of such abuse as indicated by the laboratory results during the Screening assessments
- 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
- Known hypersensitivity to setrusumab or excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ultragenyx Pharmaceutical Inclead
- Mereo BioPharmacollaborator
Study Sites (44)
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Shriners Hospital for Children - Northern California
Sacramento, California, 95817, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
Nemours/ Alfred i. duPoint Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of South Florida
Tampa, Florida, 33612, United States
Shriners Hospitals for Children - Chicago
Chicago, Illinois, 60707, United States
Indiana University Hospital
Indianapolis, Indiana, 46202, United States
Kennedy Krieger Institute
Baltimore, Maryland, 21205, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Children's Hospital and Medical Center
Omaha, Nebraska, 68114, United States
New Mexico Clinical Research & Osteoporosis Center, Inc.
Albuquerque, New Mexico, 87106, United States
Atrium Health Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Nationwide Children's Hospital- Ohio State University College of Medicine
Columbus, Ohio, 43205, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
UW Health University Hospital
Madison, Wisconsin, 53792, United States
Queensland Paediatric Endocrinology
South Brisbane, Queensland, QLD 4101, Australia
Royal Children's Hospital
Melbourne, Australia
London Health Sciences Center
London, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
McGill University Health Centre
Montreal, H4A 3J1, Canada
University of Toronto- The Hospital for Sick Children (SickKids)
Toronto, Canada
Institut Imagine
Paris, France
University of Cologne
Cologne, Germany
Otto von Guericke University Magdeburg
Magdeburg, 39106, Germany
Musculoskeletal Center Würzburg
Würzburg, 97074, Germany
Istituto Ortopedico Rizzoli
Bologna, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I
Rome, 00161, Italy
Universita Degli Studi Di Verona
Verona, Italy
Wilhelmina Children's Hospital
Utrecht, Netherlands
Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych
Lodz, Poland
Hospital de Santa Maria
Lisbon, 1649-028, Portugal
Centro Hospitalar do Porto
Porto, 4099-001, Portugal
Gazi University
Ankara, Turkey (Türkiye)
Marmara University
Istanbul, Turkey (Türkiye)
Royal Manchester Childrens Hospital
Manchester, United Kingdom
Sheffield Children's NHS Foundation Trust
Sheffield, S10 2TH, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Ultragenyx Medical Director
Ultragenyx Pharmaceutical Inc
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 8, 2021
First Posted
November 18, 2021
Study Start
February 21, 2022
Primary Completion
October 20, 2025
Study Completion (Estimated)
April 1, 2027
Last Updated
February 25, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share