Setrusumab for Osteogenesis Imperfecta

(Orbit Trial)

Recruiting at 69 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

182 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objectives of the study are to identify a setrusumab dosing strategy in participants with OI and to evaluate the effect of setrusumab vs placebo on reduction in fracture rate.

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.

What data supports the effectiveness of the drug Setrusumab for treating osteogenesis imperfecta?

Research on similar drugs like Denosumab, which is used for osteoporosis and has shown promise in treating children with osteogenesis imperfecta, suggests that targeting bone health can be effective. Additionally, bisphosphonates, another class of drugs, have been shown to increase bone density and reduce fractures in osteogenesis imperfecta patients. ^{1 2 3 4 5}

Research Team

Ultragenyx Medical Director

Principal Investigator

Ultragenyx Pharmaceutical Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Individualized treatment with denosumab in children with osteogenesis imperfecta - follow up of a trial cohort. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Oral Bisphosphonate Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta-Analysis of Six Randomized Placebo-Controlled Trials. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Skeletal outcomes of patients with osteogenesis imperfecta during drug holiday of bisphosphonates: a real-world study. [2022]