A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804

NCT03118570 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MBPS2052016-005096-27
• Study Type: interventional
• Target: 112
• Locations: 5 countries
• Sites: 25

Brief Summary

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. Participants will be treated for 12 months and followed up for a further 12 months.

Conditions

Osteogenesis Imperfecta, Type I; Osteogenesis Imperfecta Type III; Osteogenesis Imperfecta Type IV

Keywords

Osteogenesis Imperfecta; Brittle Bone Disease

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12

  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).

  Baseline, Month 12 (end of treatment [EOT])

• Change From Baseline in Radial Bone Strength (Failure Load) at Month 12

  Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.

  Baseline, Month 12 (EOT)

• Change From Baseline in Radial Bone Strength (Stiffness) at Month 12

  Assessed by FEA of models generated from HRpQCT images of the distal radius.

  Baseline, Month 12 (EOT)

Secondary Outcomes (25)

• Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set

  Baseline, Months 6, 12 (EOT), 18, 24

• Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm

  Baseline, Months 6, 12 (EOT)

• Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set

  Baseline, Months 6, 12 (EOT), 18, 24

• Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm

  Baseline, Months 6, 12 (EOT)

• Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set

  Baseline, Months 6, 12 (EOT), 18, 24

Study Arms (5)

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.

Drug: setrusumab; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D; Drug: zoledronic acid (optional)

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.

Drug: setrusumab; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D; Drug: zoledronic acid (optional)

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.

Drug: setrusumab; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D; Drug: zoledronic acid (optional)

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.

Drug: setrusumab; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D; Drug: zoledronic acid (optional)

Placebo

PLACEBO COMPARATOR

Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

Dietary Supplement: Calcium; Dietary Supplement: Vitamin D

Interventions

setrusumab DRUG

Intravenous infusion

Also known as: BPS804

Setrusumab 2 mg/kg (Blinded); Setrusumab 20 mg/kg (Blinded); Setrusumab 20 mg/kg (Open-Label); Setrusumab 8 mg/kg (Blinded)

Calcium DIETARY_SUPPLEMENT

tablets

Placebo; Setrusumab 2 mg/kg (Blinded); Setrusumab 20 mg/kg (Blinded); Setrusumab 20 mg/kg (Open-Label); Setrusumab 8 mg/kg (Blinded)

Vitamin D DIETARY_SUPPLEMENT

capsules

Placebo; Setrusumab 2 mg/kg (Blinded); Setrusumab 20 mg/kg (Blinded); Setrusumab 20 mg/kg (Open-Label); Setrusumab 8 mg/kg (Blinded)

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.

Setrusumab 2 mg/kg (Blinded); Setrusumab 20 mg/kg (Blinded); Setrusumab 20 mg/kg (Open-Label); Setrusumab 8 mg/kg (Blinded)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a clinical diagnosis of OI Type I, III or IV with a confirmed defect in the COL1A1/COL1A2 genes, as confirmed by genetic testing
• One or more fractures in the past 5 years
• Capable of giving signed consent

You may not qualify if:

• History of skeletal malignancies or other bone diseases (other than OI)
• History of neural foraminal stenosis (except if due to scoliosis)
• History of myocardial infarction, angina pectoris, ischaemic stroke or transient ischaemic attack
• History of endocrine or thyroid/parathyroid conditions that could affect bone metabolism
• Treatment with bisphosphonates within 3 months of randomisation
• Treatment with teraparatide, denosumab or other anabolic/anti-reabsorptive medications within 6 months of randomisation

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead
• Mereo BioPharma: collaborator

Study Sites (25)

Mereo Investigator Site

Birmingham, Alabama, 35294, United States

Location

Mereo Investigator Site

Jacksonville, Florida, 32207, United States

Location

Mereo Investigator Site

Baltimore, Maryland, 21287, United States

Location

Mereo Investigator Site

Boston, Massachusetts, 012115, United States

Location

Mereo Investigator Site

Saint Paul, Minnesota, 55101, United States

Location

Mereo Investigator Site

St Louis, Missouri, 63110, United States

Location

Mereo Investigator Site

Albuquerque, New Mexico, 87106, United States

Location

Mereo Investigator Site

Cincinnati, Ohio, 45229, United States

Location

Mereo Investigator Site

Portland, Oregon, 97239, United States

Location

Mereo Investigator Site

Pittsburgh, Pennsylvania, 15225, United States

Location

Mereo Investigator Site

Nashville, Tennessee, 37232, United States

Location

Mereo Investigator Site

Houston, Texas, 77030, United States

Location

Mereo Investigator Site

Toronto, Ontario, Canada

Location

Mereo Investigator Site

Montreal, Quebec, Canada

Location

Mereo Investigator Site

Québec, Quebec, Canada

Location

Mereo Investigator Site

Aarhus, Denmark

Location

Mereo Investigator Site

Odense, Denmark

Location

Mereo Investigator Site

Paris, Paris Cedex 14, France

Location

Mereo Investigator Site

Lyon, France

Location

Mereo Investigator Site

Paris, France

Location

Mereo Investigator Site

Cambridge, Cambridgeshire, United Kingdom

Location

Mereo Investigator Site

Newcastle upon Tyne, Newcastle, United Kingdom

Location

Mereo Investigator Site

Oxford, Oxfordshire, United Kingdom

Location

Mereo Investigator Site

Bristol, United Kingdom

Location

Mereo Investigator Site

London, United Kingdom

Location

MeSH Terms

Conditions

Osteogenesis Imperfecta; Osteogenesis imperfecta, type 3

Interventions

setrusumab; Calcium; Vitamin D; Zoledronic Acid

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Study Officials

• Medical Director

  Mereo BioPharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor will be masked until the primary analysis of the study except for open-label substudy treatment arm. The study site pharmacist will be unmasked to treatment allocation throughout. Study treatment will be monitored by a separate unmasked monitoring team.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, Dose-finding Study, incorporating an open-label substudy

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 18, 2017
• Study Start: September 11, 2017
• Primary Completion: October 1, 2019
• Study Completion: November 12, 2020
• Last Updated: July 5, 2023
• Results First Posted: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); CA (3); US (12); FR (3); DK (2)