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Study to Assess the Efficacy and Safety of Setrusumab in Participants With Osteogenesis Imperfecta

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05125809
Recruitment Status : Recruiting
First Posted : November 18, 2021
Last Update Posted : August 2, 2022
Sponsor:
Collaborator:
Mereo BioPharma
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

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.

Condition or disease Intervention/treatment Phase
Osteogenesis Imperfecta Biological: Setrusumab Other: Placebo Phase 2 Phase 3

Detailed Description:
Participants in Phase 2 will be randomized 1:1:1 to receive setrusumab (low or high dose) or placebo. Participants will continue receiving their assigned dose until the selected dosing strategy is determined. Once selected, Phase 2 participants will remain double-blind and those assigned to setrusumab will begin receiving setrusumab at the selected dosing strategy, and participants in the placebo group will continue receiving placebo. Phase 3 participants will be randomized 2:1 to receive setrusumab (at the dose[s] selected in the primary analysis of Phase 2 period) or placebo. Treatment assignments will remain blinded throughout the study. Participants will transition to an open-label Treatment Extension Period after the Phase 3 primary analysis is complete, or once a participant has completed 24 months of treatment in the double-blind period, whichever is sooner. Participants in the Treatment Extension period will receive open-label setrusumab treatment for at least 12 months or until commercial availability in their respective regions (whichever occurs first).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 231 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study to Assess the Efficacy and Safety of Setrusumab in Subjects With Osteogenesis Imperfecta
Actual Study Start Date : February 21, 2022
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2026


Arm Intervention/treatment
Placebo Comparator: Placebo -> Placebo -> Open Label (OL) Setrusumab

Double-blind placebo during phase 2 followed by double-blind placebo followed by open-label setrusumab

During treatment and treatment extension periods, participants will receive daily supplementation with calcium and vitamin D as directed by the treating physician

Biological: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other Names:
  • BPS804
  • UX143

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

Experimental: Low Dose Setrusumab -> Setrusumab Selected Dose -> OL Setrusumab

Double-blind setrusumab low dose during phase 2 followed by double-blind setrusumab selected dose followed by open-label setrusumab

During treatment and treatment extension periods, participants will receive daily supplementation with calcium and vitamin D as directed by the treating physician

Biological: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other Names:
  • BPS804
  • UX143

Experimental: High Dose Setrusumab -> Setrusumab Selected Dose -> OL Setrusumab

Double-blind setrusumab high dose during phase 2 followed by double-blind setrusumab selected dose followed by open-label setrusumab

During treatment and treatment extension periods, participants will receive daily supplementation with calcium and vitamin D as directed by the treating physician

Biological: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other Names:
  • BPS804
  • UX143

Experimental: Setrusumab Selected Dose -> OL Setrusumab

Double-blind setrusumab selected dose during phase 3 followed by open-label setrusumab

During treatment and treatment extension periods, participants will receive daily supplementation with calcium and vitamin D as directed by the treating physician

Biological: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other Names:
  • BPS804
  • UX143

Placebo Comparator: Placebo -> OL Setrusumab

Double-blind placebo during phase 3 followed by open-label setrusumab

During treatment and treatment extension periods, participants will receive daily supplementation with calcium and vitamin D as directed by the treating physician

Biological: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other Names:
  • BPS804
  • UX143

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




Primary Outcome Measures :
  1. Phase 2: Percent Change in Serum Amino-terminal Propeptide of Type 1 Procollagen (P1NP) from Baseline at Month 1 [ Time Frame: Baseline, Month 1 ]
  2. Phase 3: Annualized Rate of all Radiographically-confirmed Fractures, Excluding Morphometric Vertebral Fractures, During the Double-blind Treatment Period [ Time Frame: Up to Month 24 ]

Secondary Outcome Measures :
  1. Phase 2: Serum Setrusumab Concentration [ Time Frame: From Predose up to Month 24 ]
  2. Phase 2: Baseline-Corrected Area Under the Effect Curve (AUEC) for Serum P1NP Over a 2-Month Period [ Time Frame: Baseline, Up to Month 2 ]
  3. Phase 2: Percent Change from Baseline for Serum P1NP Over a 2-Month Period [ Time Frame: Baseline, Up to Month 2 ]
  4. Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Cross-linked C-telopeptide of Type I Collagen (CTx) [ Time Frame: Baseline, Up to Month 24 ]
  5. Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Bone-specific Alkaline Phosphatase (BSAP) [ Time Frame: Baseline, Up to Month 24 ]
  6. Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Osteocalcin (OCN) [ Time Frame: Baseline, Up to Month 24 ]
  7. Phase 2: Change from Baseline in Dual Energy X-ray (DXA) Lumbar Spine Bone Mineral Density (BMD) Z-score [ Time Frame: Baseline, Up to Month 24 ]
  8. Phase 2: Percent Change from Baseline in DXA Lumbar Spine BMD [ Time Frame: Baseline, Up to Month 24 ]
  9. Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Month 24 ]
  10. Phase 2: Number of Participants With Anti-setrusumab Binding and Neutralizing Antibodies at scheduled Timepoints [ Time Frame: Up to Month 24 ]
  11. Phase 3: Annualized Rate of all Radiographically-confirmed Fractures, Including Morphometric Vertebral Fractures, During the Double-blind Treatment Period [ Time Frame: Up to Month 24 ]
  12. Phase 3: Change from Baseline in DXA Lumbar Spine BMD Z-score at 18 Months [ Time Frame: Baseline, Month 18 ]
  13. Phase 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Physical Functioning Scale for Pediatric Participants at 18 Months [ Time Frame: Baseline, Month 18 ]
  14. Phase 3: Change from Baseline in PedsQL Physical Health Summary Score for Pediatric Participants at 18 Months [ Time Frame: Baseline, Month 18 ]
  15. Phase 3: Change from Baseline in 36-item Short Form Health Survey (SF-36) for Adult Participants at 18 Months [ Time Frame: Baseline, Month 18 ]
  16. Phase 3: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Month 24 ]
  17. Phase 3: Number of Participants With Anti-setrusumab Binding and Neutralizing Antibodies at Scheduled Timepoints [ Time Frame: Up to Month 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of OI Types I, III, or IV as confirmed by identification of genetic mutation in collagen, type I, alpha 1 (COL1A1) or collagen, type I, alpha 2 (COLA2)
  • ≥ 1 fracture in the past 12 months or ≥ 2 fractures in the past 24 months
  • Serum 25 hydroxyvitamin D ≥ 20 ng/mL at the Screening Visit. If levels are below the normal range, assuming a subject meets all other eligibility requirements, the subject may be rescreened after a minimum of 14 days of supplementation as directed by their 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 prior medical records for the collection of historical 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:

  • For Phase 2 Only: A history of bone surgery within the previous 6 months prior to Screening or planned bone surgery for new hardware placement for next 18 months
  • History of skeletal malignancies or bone metastases at any time
  • History of neural foraminal stenosis (except if due to scoliosis)
  • 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. Bisphosphonate use prior to Screening within a period that is at least the length of the dosing interval of bisphosphonate use (eg, ≥ 3 months off bisphosphonates if bisphosphonate dosing was every 3 months). The required time for being off bisphosphonates should not exceed 6 months (eg, patients who were dosed with bisphosphonates every 12 months can enroll if they have not received bisphosphonates within 6 months prior to Screening).
    2. Teriparatide, growth hormone, or other anabolic or anti-resorptive medications within 6 months of Screening
    3. Denosumab within 24 months of Screening
  • 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 their excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
  • History of external radiation
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05125809


Contacts
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Contact: Patient Contact: Trial Recruitment 1-888-756-8657 trialrecruitment@ultragenyx.com
Contact: HCP Contact: Medical Information 1-888-756-8657 medinfo@ultragenyx.com

Locations
Show Show 38 study locations
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Mereo BioPharma
Investigators
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Study Director: Ultragenyx Medical Director Ultragenyx Pharmaceutical Inc
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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT05125809    
Other Study ID Numbers: UX143-CL301
2021-006597-23 ( EudraCT Number )
First Posted: November 18, 2021    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases