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Also known as setrusumab, UX143
BPS804 · 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 ...
BPS804 is an investigational monoclonal antibody developed by Ultragenyx Pharmaceutical Inc. (ticker RARE) for rare bone disorders. It has been studied in Phase 2 clinical trials in hypophosphatasia, osteogenesis imperfecta, and osteopenia. It is not an approved therapy and remains in clinical development.
BPS804 has been studied in hypophosphatasia as an investigational treatment for adults with the condition. A Phase 2 dose escalation study evaluated the safety and tolerability of multiple infusions of BPS804 in adults with hypophosphatasia. The drug has also been studied in osteogenesis imperfecta and osteopenia, but it is not approved for any indication.
BPS804 is developed by Ultragenyx Pharmaceutical Inc., which trades on the Nasdaq under the ticker RARE. Ultragenyx is a biopharmaceutical company focused on rare and ultra-rare genetic diseases, and BPS804 is part of its clinical-stage pipeline.
BPS804 is in Phase 2 clinical development. All of its reported trials were Phase 2 studies, and those trials have been completed. The drug is investigational and has not been approved by the FDA for hypophosphatasia, osteogenesis imperfecta, osteopenia, or any other indication.
BPS804 has been evaluated in three completed Phase 2 trials: NCT01417091 in osteogenesis imperfecta, NCT01406977 in hypophosphatasia, and NCT01406548 in postmenopausal women with low bone mineral density. These studies enrolled a combined total of 44 participants across sites in the United States, Belgium, Canada, and Germany.