Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BPS804, UX143
Setrusumab · 7 trials · 7 indications
Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).
Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.
Assessed by FEA of models generated from HRpQCT images of the distal radius.
The assessment of safety will be based on primarily on the frequency of adverse events, laboratory abnormalities, and serious adverse events suspected by the investigators to be related to study treatments. The AE collection period extends from the time of first study drug administration drug until study completion. The intensity of each AE will be characterized and classified into 1 of the 3 generic categories (mild, moderate, or severe). The number and percentage of patients with adverse events will be tabulated by treatment group, body system and preferred term. The periods for adverse event tabulation will be from dose administration up to next dose administration if a further dose is given, and from dose administration to EOS for the last dose administration of a patient.
Biomarker data from serum bone formation biomarkers: procollagen type I N-terminal propeptide, procollagen type I C-terminal propeptide, osteocalcin, and bone-specific alkaline phosphatase, and from serum bone resporption mbiomarkers: C-telopeptides of type I collagen cross-links, and N-telopeptides of type I collagen cross-links will be reported as concentration results, measured using a specific assay with a working range defined by the Lower limit of quantification and Upper limit of quantification. It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 43.
Bone mineral density will be assessed by dual-energy X-ray absorptiometry of the lumbar spine. Analysis will include four vertebral levels from L1 to L4. Individual vertebral levels may be excluded due to artifact. Bone mineral density Z-scores will be used as these are a comparison of a patient's BMD to that of a patient of the same age, sex, and ethnicity. The comparison of change from baseline with the matching change in the reference group will be done by 2-sample t-tests (1-sided). It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05) increase versus baseline in the BPS804 group on day 141.
| Arm | Type | Description |
|---|---|---|
| Setrusumab | EXPERIMENTAL | - |
| Intravenous Bisphosphonates (IV-BP) -> Setrusumab | ACTIVE_COMPARATOR | Participants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator. After the active-controlled period, participants will receive Setrusumab during the extension period |
| Low Dose Setrusumab -> Open-Label (OL) Setrusumab Selected Dose | EXPERIMENTAL | 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 |
| High Dose Setrusumab -> OL Setrusumab Selected Dose | EXPERIMENTAL | 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 |
| Setrusumab Selected Dose -> OL Setrusumab Selected Dose | EXPERIMENTAL | 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 -> OL Setrusumab Selected Dose | PLACEBO_COMPARATOR | 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 |
| Setrusumab 20 mg/kg (Blinded) | EXPERIMENTAL | Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Setrusumab 8 mg/kg (Blinded) | EXPERIMENTAL | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Setrusumab 2 mg/kg (Blinded) | EXPERIMENTAL | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Setrusumab 20 mg/kg (Open-Label) | EXPERIMENTAL | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Placebo | PLACEBO_COMPARATOR | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| BPS804 dosing frequency 1 | EXPERIMENTAL | Subjects dosed 20mg/Kg BPS804 monthly |
| placebo dosing frequency 1 | PLACEBO_COMPARATOR | Subjects dosed with matching placebo to 20mg/Kg BPS804 monthly |
| BPS804 dosing frequency 2 | EXPERIMENTAL | Subjects dosed with 20mg/Kg BPS804 quarterly |
| placebo dosing frequency 2 | PLACEBO_COMPARATOR | Subjects dosed with matching placebo to 20mg/Kg BPS804 every 3 months |
| BPS804 dosing frequency 3 | EXPERIMENTAL | Subjects dosed with 20mg/Kg BPS804 weekly |
| Placebo dosing frequency 3 | PLACEBO_COMPARATOR | Subjects dosed with matching placebo to 20mg/Kg BPS804 weekly |
| BPS804 dose escalation | EXPERIMENTAL | BPS804 IV Setrusumab given in escalating doses from 5mg/Kg to 20mg/Kg |
| Treatment group | EXPERIMENTAL | - |
| Untreated reference group | NO_INTERVENTION | - |
| Name | Type | Description |
|---|---|---|
| setrusumab | BIOLOGICAL | A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion |
| Bisphosphonate | DRUG | Administered per investigator discretion via intravenous (IV) infusion |
| Placebo | OTHER | A 5% dextrose/glucose solution administered QM via IV infusion |
| Calcium | DIETARY_SUPPLEMENT | tablets |
| Vitamin D | DIETARY_SUPPLEMENT | capsules |
| zoledronic acid (optional) | DRUG | Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician. |
| BPS804 20mg/Kg | DRUG | - |
| Placebo to 20mg/Kg BPS804 | DRUG | - |
| BPS804 | DRUG | - |
Key Inclusion Criteria: * Clinical diagnosis of OI Type I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2 * History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months * Any prior ...
Setrusumab is an investigational monoclonal antibody being developed for osteogenesis imperfecta, a rare genetic bone disorder. It is being studied in pediatric and adult patients, including type I osteogenesis imperfecta. Ultragenyx Pharmaceutical Inc. holds a Breakthrough Therapy designation from the FDA for this program.
Setrusumab targets SOST, also known as sclerostin. It is an inhibitor of this target, which is a protein that normally suppresses bone formation. By inhibiting sclerostin, setrusumab is designed to increase bone formation and bone mass in patients with osteogenesis imperfecta.
Setrusumab is being developed by Ultragenyx Pharmaceutical Inc., which trades on the Nasdaq under the ticker RARE. The company is running the clinical development program for the drug in osteogenesis imperfecta, including Phase 3 studies in pediatric patients.
Setrusumab is in Phase 3 clinical development. It is an investigational therapy and has not been approved by the FDA. The program includes Phase 3 trials in pediatric patients with osteogenesis imperfecta, along with earlier Phase 2 studies in pediatric and adult patients.
Setrusumab is being studied in several trials, including NCT06636071 in pediatric Japanese subjects, NCT05768854 comparing setrusumab with bisphosphonates in pediatric patients, and NCT05125809 comparing setrusumab with placebo. A completed Phase 2 study, NCT03118570, evaluated the drug in adults with type I, III, or IV osteogenesis imperfecta.
Yes, setrusumab was previously known as BPS804. The completed Phase 2 study NCT03118570 in adults with type I, III, or IV osteogenesis imperfecta was conducted under the BPS804 name. Both names refer to the same monoclonal antibody targeting SOST.