Setrusumab for Osteogenesis Imperfecta

(Orbit Trial)

Not currently recruiting at 78 trial locations

Overseen By HCP Contact: Medical Information

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ultragenyx Pharmaceutical Inc

Must not be taking: Teriparatide, Denosumab, Romosozumab

Disqualifiers: Skeletal malignancies, Stroke, Hypocalcemia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dosing strategy for setrusumab, a treatment for osteogenesis imperfecta (OI), and to assess its ability to reduce fracture rates compared to a placebo. Participants will receive either setrusumab at varying doses or a placebo, followed by setrusumab, to evaluate its effectiveness. Suitable candidates have OI Type I, III, or IV and have experienced at least one fracture in the past year. Participants must be willing to discontinue any bisphosphonate therapy during the study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering an opportunity to contribute to significant advancements in OI treatment.

Will I have to stop taking my current medications?

The trial requires that you do not receive bisphosphonate therapy during the study. Additionally, you must not have taken certain medications like teriparatide, growth hormone, or denosumab within specific time frames before starting the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that setrusumab is generally safe for people with osteogenesis imperfecta (OI). In one study, patients who used setrusumab for 14 months experienced no serious safety problems. Another study found that setrusumab improved bone health without major side effects. Researchers are conducting more studies with larger groups to confirm these findings. Overall, setrusumab appears well-tolerated, but ongoing research will provide more information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about setrusumab for osteogenesis imperfecta because it targets the condition in a unique way. Unlike standard treatments that often focus on managing symptoms or improving bone density through supplements or bisphosphonates, setrusumab is an anti-sclerostin antibody. This means it works by inhibiting a protein that normally slows down bone formation, potentially leading to stronger bones. Additionally, setrusumab offers a more direct approach to improving bone strength, which could translate to fewer fractures and enhanced quality of life for patients.

What evidence suggests that setrusumab might be an effective treatment for osteogenesis imperfecta?

Research has shown that setrusumab holds promise for treating osteogenesis imperfecta (OI), a condition where bones break easily. One study found that setrusumab reduced the number of fractures by 67% over a year and strengthened bones by improving bone mineral density. Importantly, these benefits occurred without any serious safety concerns. In this trial, participants may receive different doses of setrusumab or a placebo, followed by an open-label phase with setrusumab. These findings suggest that setrusumab could help people with OI have stronger bones and fewer fractures. ^{3 5 6 7 8}

Who Is on the Research Team?

Ultragenyx Medical Director

Principal Investigator

Ultragenyx Pharmaceutical Inc

Are You a Good Fit for This Trial?

This trial is for people with Osteogenesis Imperfecta (OI) Types I, III, or IV who've had fractures in the past year. They must not be on bisphosphonate therapy and agree to use effective contraception. Excluded are those with certain skeletal conditions, unstable neurologic diseases, severe kidney issues, recent drug abuse, hypersensitivity to setrusumab or its components.

Inclusion Criteria

I have Osteogenesis Imperfecta Type I, III, or IV confirmed by a genetic test.

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

I agree not to take bisphosphonate therapy during the study.

Exclusion Criteria

Concurrent participation in another clinical study without prior approval from the Investigator in consultation with the Medical Monitor

I have received specific prior treatments.

I have symptoms of Chiari malformation or basilar invagination, and no unstable neurological conditions in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants receive either low dose or high dose setrusumab in a single-blind manner until the Month 6 study visit

6 months

Phase 2 Open-label Treatment Extension

Participants receive open-label setrusumab treatment following the selected dosing strategy

At least 12 months

Phase 3 Treatment

Participants receive setrusumab or placebo in a double-blind manner

Duration not specified

Phase 3 Open-label Treatment Extension

Participants transition to open-label setrusumab treatment after the double-blind period

At least 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Setrusumab

Trial Overview The study tests Setrusumab against a placebo to find the best dose and see if it lowers fracture rates in OI patients. Participants will either receive Setrusumab or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Setrusumab Selected Dose -> OL Setrusumab Selected Dose Experimental Treatment 1 Intervention

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

Group II: Low Dose Setrusumab -> Open-Label (OL) Setrusumab Selected Dose Experimental Treatment 1 Intervention

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

Group III: High Dose Setrusumab -> OL Setrusumab Selected Dose Experimental Treatment 1 Intervention

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

Group IV: Placebo -> OL Setrusumab Selected Dose Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Ultragenyx Pharmaceutical Inc

Lead Sponsor

Trials

94

Recruited

104,000+

Dr. Emil D. Kakkis

Ultragenyx Pharmaceutical Inc

Chief Executive Officer since 2010

MD/PhD in Biological Chemistry from UCLA

Dr. Eric Crombez

Ultragenyx Pharmaceutical Inc

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Mereo BioPharma

Industry Sponsor

Trials

23

Recruited

1,700+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39012717/

Setrusumab for the treatment of osteogenesis imperfecta Overall, setrusumab improved the bones of patients with OI with no serious safety concerns. More studies will include even more patients to see ...

2. ir.ultragenyx.com ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-and-mereo-biopharma-announce-interim-phase-2-data

Ultragenyx and Mereo BioPharma Announce Interim ... Treatment with setrusumab resulted in 67% reduction in annualized fracture rate associated with continuous and meaningful improvements in bone mineral density ...

3. academic.oup.com academic.oup.com/jbmr/article/39/9/1215/7714798

12-month results from the phase 2b asteroid study | Journal of ... Overall, setrusumab improved the bones of patients with OI with no serious safety concerns. More studies will include even more patients to see ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03118570

NCT03118570 | A Study in Adult Patients With Type I, III or ... The purpose of this study is to select a suitable dose of BPS804 by measuring the strength/quality of bone using a special type of CT scanner.

5. yalemedicine.org yalemedicine.org/clinical-trials/efficacy-and-safety-of-setrusumab-in-subjects-with-osteogenesis-imperfecta-1

Study to Assess the Efficacy and Safety of Setrusumab in ... The primary objectives of the study are to identify a dose(s) of setrusumab based on safety and pharmacodynamic (PD) effects in participants with OI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11454541/

Updated Phase 2 Data From The Phase 2/3 Orbit Study In the ongoing Phase 2/3 Orbit study (NCT05125809), Phase 2 evaluated the efficacy and safety of setrusumab in pediatric and young-adult cohorts with OI based ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01417091

Study Details | NCT01417091 | Safety, Pharmacokinetics ... This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2949774425009355

P052: Durable fracture rate reduction in patients with OI ... The present study examines key safety and efficacy outcomes in pediatric and young-adult participants with OI following 14 months of setrusumab treatment.