Setrusumab vs Placebo for Osteogenesis Imperfecta

NCT ID: NCT05125809

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-21
• Study Completion Date: 2027-04-30

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.

Detailed Description

Participants in Phase 2 will be randomized 1:1 to receive low dose or high dose setrusumab. Phase 2 participants will continue receiving their assigned dose of setrusumab until all Phase 2 participants have completed the Month 6 study visit. After this point, Phase 2 participants will begin receiving the selected dosing strategy in the Phase 2 open-label Treatment Extension Period. Phase 3 participants will be randomized 2:1 to receive setrusumab or placebo during the double-blind treatment period. Phase 3 participants will transition to the open-label Treatment Extension Period after the end of the double-blind period. Participants in the Phase 2 and Phase 3 treatment extension periods will receive open-label setrusumab treatment for at least 12 months, and have the option to remain in the open-label treatment period until setrusumab is commercially available in their region. An optional substudy will be conducted in approximately 10 participants (≥ 8 years) consisting of a bone biopsy to investigate the impact of setrusumab on bone histomorphology.

Conditions

Osteogenesis Imperfecta

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low Dose Setrusumab -> Open-Label (OL) Setrusumab Selected Dose

Single-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

Group Type: EXPERIMENTAL

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

High Dose Setrusumab -> OL Setrusumab Selected Dose

Single-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

Group Type: EXPERIMENTAL

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Setrusumab Selected Dose -> OL Setrusumab Selected Dose

Double-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

Group Type: EXPERIMENTAL

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Placebo -> OL Setrusumab Selected Dose

Double-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

Group Type: PLACEBO_COMPARATOR

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Placebo

Intervention Type: OTHER

A 5% dextrose/glucose solution administered QM via IV infusion

Interventions

Setrusumab

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Intervention Type: BIOLOGICAL

Placebo

A 5% dextrose/glucose solution administered QM via IV infusion

Intervention Type: OTHER

Other Intervention Names

BPS804; UX143

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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:

1. Teriparatide, growth hormone, bone anabolic, or anti-resorptive medications (other than bisphosphonates) within 6 months of the first dose with study drug (Month 0)

2. Denosumab within 24 months of Screening

3. 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
• History of external radiation therapy
• Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study
• Use of any investigational product or investigational medical device within 4 weeks or 5 half-lives of investigational drug (whichever is longer) 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 Investigator in consultation with the Medical Monitor
• For Phase 2 Only: A history of bone surgery within the previous 6 months prior to Screening or planned bone surgery for the first 3 months of the study

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mereo BioPharma

INDUSTRY

Sponsor Role: collaborator

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ultragenyx Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Shriners Hospital for Children - Northern California

Sacramento, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Nemours/ Alfred i. duPoint Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

University of South Florida

Tampa, Florida, United States

Shriners Hospitals for Children - Chicago

Chicago, Illinois, United States

Indiana University Hospital

Indianapolis, Indiana, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Children's Hospital and Medical Center

Omaha, Nebraska, United States

New Mexico Clinical Research & Osteoporosis Center, Inc.

Albuquerque, New Mexico, United States

Atrium Health Levine Children's Hospital

Charlotte, North Carolina, United States

Nationwide Children's Hospital- Ohio State University College of Medicine

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

UW Health University Hospital

Madison, Wisconsin, United States

Queensland Paediatric Endocrinology

South Brisbane, Queensland, Australia

Royal Children's Hospital

Melbourne, , Australia

London Health Sciences Center

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

McGill University Health Centre

Montreal, , 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, , Germany

Musculoskeletal Center Würzburg

Würzburg, , Germany

Istituto Ortopedico Rizzoli

Bologna, , Italy

Azienda Ospedaliera Universitaria Policlinico Umberto I

Rome, , 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, , Portugal

Centro Hospitalar do Porto

Porto, , 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, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Italy; Netherlands; Poland; Portugal; Turkey (Türkiye); United Kingdom

Related Links

https://www.ultraclinicaltrials.com/OI

Ultragenyx Osteogenesis Imperfecta (OI) Research Study

https://www.ultragenyx.com/our-research/our-clinical-trial-transparency-commitment/

Ultragenyx Transparency Commitment

Other Identifiers

2021-006597-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-510919-29-00

Identifier Type: CTIS

Identifier Source: secondary_id

UX143-CL301

Identifier Type: -

Identifier Source: org_study_id