SETRUSUMAB for Osteogenesis imperfecta

Inclusion criteria

• {"criterion_text":"- Males and females 5 to < 26 years of age at time of informed consent"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- ≥ 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"}
• {"criterion_text":"- 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 be repeated after a minimum of 14 days of vitamin D supplementation as directed by the treating physician"}
• {"criterion_text":"- Willing to not receive bisphosphonate therapy during the study"}
• {"criterion_text":"- From the period following informed consent to 60 days after the last dose of 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"}
• {"criterion_text":"- Willing and able to provide informed consent for subjects ≥ 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"}
• {"criterion_text":"- Willing to provide access to medical records for the collection of radiographic data, fracture data, growth data, and disease history"}
• {"criterion_text":"- 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

• {"criterion_text":"- For Phase 2 subjects only, a history of major bone surgery within the previous 6 months prior to Screening or planned major bone surgery for the first 3 months of the study"}
• {"criterion_text":"- Prior treatment with the following: a. Teriparatide, growth hormone, bone anabolic, or anti-resorptive medications (other than bisphosphonates) within 6 months of the first dose with study drug (Month 0) b. Denosumab within 24 months of the first dose with study drug (Month 0) c. Romosozumab at any time"}
• {"criterion_text":"- Documented alcohol and/or drug abuse within 12 months prior to dosing or evidence of such abuse, as determined by the Investigator"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects"}
• {"criterion_text":"- History of external radiation therapy"}
• {"criterion_text":"- Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Concurrent participation in another clinical study without prior approval from the Investigator in consultation with the Medical Monitor"}
• {"criterion_text":"- History of skeletal malignancies or bone metastases at any time"}
• {"criterion_text":"- History of neural foraminal stenosis (except if due to scoliosis)"}
• {"criterion_text":"- Clinically unstable manifestations of Chiari malformation or basilar invagination within the past 2 years. Presence of any other neurologic disease that has been clinically unstable within the past 2 years requires review by the Medical Monitor."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Rickets or any skeletal condition (other than OI) leading to bone deformities and/or increased risk of fractures"}
• {"criterion_text":"- History of stroke, myocardial infarction, TIA, or angina. Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with other cardiovascular risk factors such as hypertension, hyperlipidemia, familial hyperlipidemia, family history of premature ischemic cardiovascular disease, smoking, diabetes mellitus, and metabolic syndrome."}
• {"criterion_text":"- Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limits after a ≥ 4 hour fast"}
• {"criterion_text":"- Estimated glomerular filtration rate ≤ 29 mL/min/1.73 m2"}

Primary endpoints

• {"endpoint_text":"- Phase II: Percent change in serum P1NP from Baseline at Month 1","definition_or_measurement_approach":"Percent change in serum P1NP from baseline measured at Month 1 (serum biomarker measurement at scheduled time point)"}
• {"endpoint_text":"- Phase III: Annualized rate of all radiographically-confirmed fractures, excluding morphometric vertebral fractures and fractures of the fingers, toes, face, and skull, at the primary analysis","definition_or_measurement_approach":"Annualized rate calculated from radiographically-confirmed fractures at the primary analysis; specified exclusions (morphometric vertebral fractures and fractures of fingers, toes, face, skull) apply"}

Secondary endpoints

• {"endpoint_text":"- Phase II: Serum setrusumab concentration at scheduled time points","definition_or_measurement_approach":"Serum pharmacokinetic concentration measurements of setrusumab at scheduled time points"}
• {"endpoint_text":"- Phase II - Baseline-corrected AUEC for serum P1NP over a 1- and 2-month timeframe","definition_or_measurement_approach":"Area under the effect curve (AUEC) for serum P1NP corrected for baseline over 1- and 2-month intervals"}
• {"endpoint_text":"- Phase II - Percent change from Baseline in bone turnover markers (P1NP and OCN) over time","definition_or_measurement_approach":"Percent change from baseline in bone turnover biomarkers P1NP and osteocalcin (OCN) measured over time"}
• {"endpoint_text":"- Phase II - Change from Baseline in DXA lumbar spine BMD z-scores over time","definition_or_measurement_approach":"Change from baseline in lumbar spine bone mineral density (BMD) z-scores measured by DXA over time"}
• {"endpoint_text":"- Phase II - Percent change from Baseline in DXA lumbar spine BMD over time","definition_or_measurement_approach":"Percent change from baseline in lumbar spine BMD measured by DXA over time"}
• {"endpoint_text":"- Phase II - Frequency, severity, and relationship to treatment of TEAEs, SAEs, AESIs","definition_or_measurement_approach":"Adverse event monitoring capturing treatment-emergent AEs, serious AEs, and adverse events of special interest with frequency, severity and investigator-assessed relationship to treatment"}
• {"endpoint_text":"- Phase II - Incidence of anti-setrusumab binding and neutralizing antibodies at scheduled time points","definition_or_measurement_approach":"Immunogenicity assessments: incidence of binding and neutralizing anti-setrusumab antibodies at scheduled time points"}
• {"endpoint_text":"- Key Secondary Endpoints: Phase III - Annualized rate of all radiographically-confirmed fractures, excluding morphometric vertebral fractures, but including fractures of the fingers, toes, face and skull, at the primary analysis","definition_or_measurement_approach":"Annualized rate from radiographically-confirmed fractures at primary analysis including specified fracture types"}
• {"endpoint_text":"- Key Secondary Endpoints: Phase III - Annualized rate of all radiographically-confirmed fractures at the primary analysis","definition_or_measurement_approach":"Annualized rate of all radiographically-confirmed fractures at the primary analysis"}
• {"endpoint_text":"- Key Secondary Endpoints: Phase III - Change from Baseline in DXA lumbar spine BMD z-score at the primary analysis","definition_or_measurement_approach":"Change from baseline in lumbar spine DXA BMD z-score measured at the primary analysis"}
• {"endpoint_text":"- Phase III - Change from Baseline at the primary analysis for: • POSNA-PODCI Sports/Physical Functioning and Pain/comfort subscale scores for subjects < 18 years of age at screening • SF-36 PF and BP Domain Scales for subjects ≥ 18 years of age at screening","definition_or_measurement_approach":"Clinical outcome assessments: POSNA-PODCI subscales for <18 and SF-36 Physical Functioning and Bodily Pain domains for ≥18 measured change from baseline at primary analysis"}
• {"endpoint_text":"- Phase III - Frequency, severity, and relationship to treatment of TEAEs, SAEs, and AESIs","definition_or_measurement_approach":"Safety monitoring of TEAEs, SAEs and AESIs with frequency, severity and relationship to treatment"}
• {"endpoint_text":"- Phase III - Incidence of binding and neutralizing anti-setrusumab antibodies at scheduled time points","definition_or_measurement_approach":"Immunogenicity assessments of binding and neutralizing anti-setrusumab antibodies at scheduled time points"}
• {"endpoint_text":"- Key Secondary Endpoints: Phase III - Proportion of subjects experiencing new radiographically confirmed fractures, excluding morphometric vertebral fractures and fractures of the fingers, toes, face, and skull at the primary analysis","definition_or_measurement_approach":"Proportion of subjects with new radiographically-confirmed fractures at the primary analysis applying specified exclusions"}

Poland

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

08-02-2026

Processing Time Days

639

Number Of Sites

1

Number Of Participants

15

Netherlands

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

726

Number Of Sites

1

Number Of Participants

9

Portugal

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

727

Number Of Sites

2

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

728

Number Of Sites

3

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

728

Number Of Sites

3

Number Of Participants

18

France

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

727

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Ultragenyx Pharmaceutical Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Medical Monitoring, Site Feasibility and Identification; additional responsibilities indicated by codes 1,12,15,2,6

Third parties

• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, Primary/ surrogate endpoint test","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Serology/ endocrinology, Primary/ surrogate endpoint test, Manage Bone-specific Alkaline Phosphatase, DKK-1, Sclerostin, Neo-epitopeCTX-1, Osteocalcin, P1NP","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Revvity Omics Sweden AB","duties_or_roles":"genetic testing for screening and eligibility confirmation","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"Primary/ surrogate endpoint test","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Aparito Limited","duties_or_roles":"Patient Reported Outcomes (ePRO)/ Quality of Life","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Medical Monitoring, Site Feasibility and Identification; other responsibilities (codes: 1,12,15,2,6)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"ECG analysis/ review","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Informed Medical Decisions Inc.","duties_or_roles":"Adjudication for genetic reports","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Drug Development Solutions Limited","duties_or_roles":"Serology/ endocrinology","organisation_type":"Pharmaceutical company"}