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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05125809
Registration number
NCT05125809
Ethics application status
Date submitted
8/11/2021
Date registered
18/11/2021
Date last updated
3/05/2024
Titles & IDs
Public title
Study to Assess Dose, Efficacy and Safety of Setrusumab in Participants With Osteogenesis Imperfecta
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Scientific title
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
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Secondary ID [1]
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2021-006597-23
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Secondary ID [2]
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UX143-CL301
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Universal Trial Number (UTN)
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Trial acronym
Orbit
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Osteogenesis Imperfecta
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Condition category
Condition code
Musculoskeletal
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Other muscular and skeletal disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Injuries and Accidents
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Fractures
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Setrusumab
Other interventions - Placebo
Experimental: 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
Experimental: 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
Experimental: 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
Placebo Comparator: 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
Other interventions: Setrusumab
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Other interventions: Placebo
A 5% dextrose/glucose solution administered QM via IV infusion
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Phase 2: Percent Change in Serum Amino-terminal Propeptide of Type 1 Procollagen (P1NP) from Baseline at Month 1
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Assessment method [1]
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Timepoint [1]
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Baseline, Month 1
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Primary outcome [2]
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Phase 3: Annualized Rate of all Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures and Fractures of the Fingers, Toes, Face, and Skull During the Double-Blind Treatment Period
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Assessment method [2]
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Timepoint [2]
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Up to Month 24
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Secondary outcome [1]
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Phase 2: Serum Setrusumab Concentration
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Assessment method [1]
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Timepoint [1]
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From Predose up to Month 24
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Secondary outcome [2]
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Phase 2: Baseline-Corrected Area Under the Effect Curve (AUEC) for Serum P1NP Over a 1 and 2-Month Period
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Assessment method [2]
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Timepoint [2]
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Baseline, Up to Month 2
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Secondary outcome [3]
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Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: P1NP
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Assessment method [3]
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Timepoint [3]
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Baseline, Up to Month 24
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Secondary outcome [4]
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Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Osteocalcin (OCN)
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Assessment method [4]
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Timepoint [4]
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Baseline, Up to Month 24
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Secondary outcome [5]
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Phase 2: Change from Baseline in Dual Energy X-ray (DXA) Lumbar Spine Bone Mineral Density (BMD) Z-score Over Time
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Assessment method [5]
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Timepoint [5]
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Baseline, Up to Month 24
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Secondary outcome [6]
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Phase 2: Percent Change from Baseline in DXA Lumbar Spine BMD Over Time
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Assessment method [6]
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Timepoint [6]
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Baseline, Up to Month 24
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Secondary outcome [7]
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Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
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Assessment method [7]
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Timepoint [7]
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Up to Month 24
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Secondary outcome [8]
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Phase 2: Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
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Assessment method [8]
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Timepoint [8]
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Up to Month 24
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Secondary outcome [9]
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Phase 3: Annualized Rate of all Radiographically-confirmed Fractures, Excluding Morphometric Vertebral Fractures, but Including Fractures of the Fingers, Toes, Face and Skull During the Double-Blind Treatment Period
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Assessment method [9]
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Timepoint [9]
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Up to Month 24
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Secondary outcome [10]
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Phase 3: Annualized Rate of All Radiographically-Confirmed Fractures During the Double-Blind Treatment Period
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Assessment method [10]
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Timepoint [10]
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Up to Month 24
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Secondary outcome [11]
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Phase 3: Change from Baseline in DXA Lumbar Spine BMD Z-score at 12 Months
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Assessment method [11]
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Timepoint [11]
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Baseline, Month 12
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Secondary outcome [12]
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Phase 3: Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning Subscale Score for Pediatric Participants at 12 Months
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Assessment method [12]
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Timepoint [12]
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Baseline, Month 12
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Secondary outcome [13]
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Phase 3: Change from Baseline in POSNA-PODCI Pain/Comfort Subscale Score for Pediatric Participants at 12 Months
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Assessment method [13]
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Timepoint [13]
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Baseline, Month 12
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Secondary outcome [14]
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Phase 3: Change from Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain Scale for Adult Participants at 12 Months
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Assessment method [14]
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Timepoint [14]
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Baseline, Month 12
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Secondary outcome [15]
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Phase 3: Change from Baseline in SF-36 Bodily Pain (BP) Domain Scale for Adult Participants at 12 Months
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Assessment method [15]
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Timepoint [15]
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Baseline, Month 12
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Secondary outcome [16]
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Phase 3: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
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Assessment method [16]
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Timepoint [16]
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Up to Month 24
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Secondary outcome [17]
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Phase 3: Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
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Assessment method [17]
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Timepoint [17]
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Up to Month 24
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Eligibility
Key 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
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Minimum age
5
Years
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Maximum age
25
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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, or other bone anabolic or anti-resorptive
medications within 6 months of Screening
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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Other
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Other design features
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Phase
Phase 2/Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
21/02/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/03/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
182
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Queensland Paediatric Endocrinology - South Brisbane
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Recruitment hospital [2]
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Royal Children's Hospital - Melbourne
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Recruitment hospital [3]
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Sydney Children's Hospital - Randwick
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Recruitment postcode(s) [1]
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QLD 4101 - South Brisbane
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Recruitment postcode(s) [2]
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- Melbourne
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Recruitment postcode(s) [3]
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- Randwick
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arkansas
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United States of America
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State/province [2]
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California
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United States of America
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State/province [3]
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Colorado
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Country [4]
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United States of America
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State/province [4]
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Connecticut
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Country [5]
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United States of America
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State/province [5]
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Delaware
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Country [6]
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United States of America
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State/province [6]
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District of Columbia
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Country [7]
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United States of America
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State/province [7]
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Florida
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Country [8]
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United States of America
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Illinois
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Country [9]
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United States of America
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Indiana
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Country [10]
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United States of America
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State/province [10]
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Maryland
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Country [11]
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United States of America
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State/province [11]
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Massachusetts
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Country [12]
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United States of America
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State/province [12]
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Missouri
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Country [13]
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United States of America
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State/province [13]
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Nebraska
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Country [14]
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United States of America
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State/province [14]
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New Mexico
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Country [15]
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United States of America
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State/province [15]
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North Carolina
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Country [16]
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United States of America
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Ohio
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Country [17]
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United States of America
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Pennsylvania
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Country [18]
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Wisconsin
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Argentina
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Buenos Aires
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Canada
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Ontario
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Canada
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Calgary
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Country [24]
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Canada
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Montréal
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Canada
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Toronto
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France
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Paris
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Germany
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Cologne
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Germany
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Magdeburg
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Germany
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Würzburg
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Italy
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State/province [30]
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Bologna
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Italy
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Rome
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Italy
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Verona
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Netherlands
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Utrecht
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Country [34]
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Poland
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State/province [34]
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Lódz
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Portugal
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Lisbon
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Portugal
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Porto
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Turkey
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Ankara
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Turkey
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Istanbul
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Country [39]
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United Kingdom
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State/province [39]
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Manchester
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Country [40]
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United Kingdom
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State/province [40]
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Sheffield
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Ultragenyx Pharmaceutical Inc
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Mereo BioPharma
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Address [1]
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05125809
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Ultragenyx Medical Director
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Address
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Ultragenyx Pharmaceutical Inc
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Phone
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Fax
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Contact person for public queries
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05125809
Download to PDF