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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05125809




Registration number
NCT05125809
Ethics application status
Date submitted
8/11/2021
Date registered
18/11/2021

Titles & IDs
Public title
Study to Assess Dose, Efficacy and Safety of Setrusumab in Participants With Osteogenesis Imperfecta
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
Secondary ID [1] 0 0
2021-006597-23
Secondary ID [2] 0 0
UX143-CL301
Universal Trial Number (UTN)
Trial acronym
Orbit
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteogenesis Imperfecta 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 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


Treatment: Other: 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
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 2: Percent Change in Serum Amino-terminal Propeptide of Type 1 Procollagen (P1NP) from Baseline at Month 1
Timepoint [1] 0 0
Baseline, Month 1
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to Month 24
Secondary outcome [1] 0 0
Phase 2: Serum Setrusumab Concentration
Timepoint [1] 0 0
From Predose up to Month 24
Secondary outcome [2] 0 0
Phase 2: Baseline-Corrected Area Under the Effect Curve (AUEC) for Serum P1NP Over a 1 and 2-Month Period
Timepoint [2] 0 0
Baseline, Up to Month 2
Secondary outcome [3] 0 0
Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: P1NP
Timepoint [3] 0 0
Baseline, Up to Month 24
Secondary outcome [4] 0 0
Phase 2: Percent Change from Baseline Over Time in Bone Turnover Marker: Osteocalcin (OCN)
Timepoint [4] 0 0
Baseline, Up to Month 24
Secondary outcome [5] 0 0
Phase 2: Change from Baseline in Dual Energy X-ray (DXA) Lumbar Spine Bone Mineral Density (BMD) Z-score Over Time
Timepoint [5] 0 0
Baseline, Up to Month 24
Secondary outcome [6] 0 0
Phase 2: Percent Change from Baseline in DXA Lumbar Spine BMD Over Time
Timepoint [6] 0 0
Baseline, Up to Month 24
Secondary outcome [7] 0 0
Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Timepoint [7] 0 0
Up to Month 24
Secondary outcome [8] 0 0
Phase 2: Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
Timepoint [8] 0 0
Up to Month 24
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Up to Month 24
Secondary outcome [10] 0 0
Phase 3: Annualized Rate of All Radiographically-Confirmed Fractures During the Double-Blind Treatment Period
Timepoint [10] 0 0
Up to Month 24
Secondary outcome [11] 0 0
Phase 3: Change from Baseline in DXA Lumbar Spine BMD Z-score at 12 Months
Timepoint [11] 0 0
Baseline, Month 12
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Baseline, Month 12
Secondary outcome [13] 0 0
Phase 3: Change from Baseline in POSNA-PODCI Pain/Comfort Subscale Score for Pediatric Participants at 12 Months
Timepoint [13] 0 0
Baseline, Month 12
Secondary outcome [14] 0 0
Phase 3: Change from Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain Scale for Adult Participants at 12 Months
Timepoint [14] 0 0
Baseline, Month 12
Secondary outcome [15] 0 0
Phase 3: Change from Baseline in SF-36 Bodily Pain (BP) Domain Scale for Adult Participants at 12 Months
Timepoint [15] 0 0
Baseline, Month 12
Secondary outcome [16] 0 0
Phase 3: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Timepoint [16] 0 0
Up to Month 24
Secondary outcome [17] 0 0
Phase 3: Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies
Timepoint [17] 0 0
Up to Month 24

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
Minimum age
5 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2026
Actual
Sample size
Target
Accrual to date
Final
182
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Paediatric Endocrinology - South Brisbane
Recruitment hospital [2] 0 0
Royal Children's Hospital - Melbourne
Recruitment hospital [3] 0 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 0 0
QLD 4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Argentina
State/province [21] 0 0
Buenos Aires
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Calgary
Country [24] 0 0
Canada
State/province [24] 0 0
Montréal
Country [25] 0 0
Canada
State/province [25] 0 0
Toronto
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
Germany
State/province [27] 0 0
Cologne
Country [28] 0 0
Germany
State/province [28] 0 0
Magdeburg
Country [29] 0 0
Germany
State/province [29] 0 0
Würzburg
Country [30] 0 0
Italy
State/province [30] 0 0
Bologna
Country [31] 0 0
Italy
State/province [31] 0 0
Rome
Country [32] 0 0
Italy
State/province [32] 0 0
Verona
Country [33] 0 0
Netherlands
State/province [33] 0 0
Utrecht
Country [34] 0 0
Poland
State/province [34] 0 0
Lódz
Country [35] 0 0
Portugal
State/province [35] 0 0
Lisbon
Country [36] 0 0
Portugal
State/province [36] 0 0
Porto
Country [37] 0 0
Turkey
State/province [37] 0 0
Ankara
Country [38] 0 0
Turkey
State/province [38] 0 0
Istanbul
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Manchester
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ultragenyx Pharmaceutical Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Mereo BioPharma
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ultragenyx Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05125809