Clinical trial NCT03118570: A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
Official title: A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab (BPS804)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteogenesis Imperfecta, Type I
Osteogenesis Imperfecta Type III
Osteogenesis Imperfecta Type IV
Keywords: Osteogenesis Imperfecta
Brittle Bone Disease
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
Collaborators: name: Mereo BioPharma
First posted: 2017-04-18
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, Dose-finding Study, incorporating an open-label substudy
Primary purpose: TREATMENT

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.

Detailed description: This study was previously posted by Mereo Biopharma and was transferred to Ultragenyx in February 2021.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12
timeFrame: Baseline, Month 12 (end of treatment [EOT])
measure: Change From Baseline in Radial Bone Strength (Failure Load) at Month 12
timeFrame: Baseline, Month 12 (EOT)
measure: Change From Baseline in Radial Bone Strength (Stiffness) at Month 12
timeFrame: Baseline, Month 12 (EOT)
Secondary outcomes:
measure: Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set
timeFrame: Baseline, Months 6, 12 (EOT), 18, 24
measure: Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set
timeFrame: Baseline, Months 6, 12 (EOT), 18, 24
measure: Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set
timeFrame: Baseline, Months 6, 12 (EOT), 18, 24
measure: Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12
timeFrame: Month 12 (EOT)
measure: Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12
timeFrame: Baseline, Month 12 (EOT)
measure: Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12
timeFrame: Baseline, Month 12 (EOT)
measure: Change From Baseline in Total vBMD (Radial and Tibial) Over Time
timeFrame: Baseline, Months 6, 12 (EOT), 18, and 24
measure: Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time
timeFrame: Baseline, Months 6, 12 (EOT), 18, and 24
measure: Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set
timeFrame: Baseline, Month 6, Month 12 (EOT)
measure: Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12
timeFrame: Baseline, Months 1, 3, 6, 9, 12 (EOT)
measure: Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12
timeFrame: Baseline, Months 1, 3, 6, 9, 12 (EOT)
measure: Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12
timeFrame: Baseline, Months 6 and 12 (EOT)
measure: Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12
timeFrame: Baseline, Months 6, 12 (EOT)
measure: Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14
timeFrame: up to Month 14
measure: Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death
timeFrame: Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Mereo Investigator Site
state: Alabama
city: Jacksonville
country: United States
facility: Mereo Investigator Site
state: Florida
city: Baltimore
country: United States
facility: Mereo Investigator Site
state: Maryland
city: Boston
country: United States
facility: Mereo Investigator Site
state: Massachusetts
city: Saint Paul
country: United States
facility: Mereo Investigator Site
state: Minnesota
city: Saint Louis
country: United States
facility: Mereo Investigator Site
state: Missouri
city: Albuquerque
country: United States
facility: Mereo Investigator Site
state: New Mexico
city: Cincinnati
country: United States
facility: Mereo Investigator Site
state: Ohio
city: Portland
country: United States
facility: Mereo Investigator Site
state: Oregon
city: Pittsburgh
country: United States
facility: Mereo Investigator Site
state: Pennsylvania
city: Nashville
country: United States
facility: Mereo Investigator Site
state: Tennessee
city: Houston
country: United States
facility: Mereo Investigator Site
state: Texas
city: Toronto
country: Canada
facility: Mereo Investigator Site
state: Ontario
city: Montreal
country: Canada
facility: Mereo Investigator Site
state: Quebec
city: Quebec City
country: Canada
facility: Mereo Investigator Site
state: Quebec
city: Aarhus
country: Denmark
facility: Mereo Investigator Site
city: Odense
country: Denmark
facility: Mereo Investigator Site
city: Paris
country: France
facility: Mereo Investigator Site
state: Paris Cedex 14
city: Lyon
country: France
facility: Mereo Investigator Site
city: Paris
country: France
facility: Mereo Investigator Site
city: Cambridge
country: United Kingdom
facility: Mereo Investigator Site
state: Cambridgeshire
city: Newcastle upon Tyne
country: United Kingdom
facility: Mereo Investigator Site
state: Newcastle
city: Oxford
country: United Kingdom
facility: Mereo Investigator Site
state: Oxfordshire
city: Bristol
country: United Kingdom
facility: Mereo Investigator Site
city: London
country: United Kingdom
facility: Mereo Investigator Site
Study officials:
affiliation: Mereo BioPharma
name: Medical Director
role: STUDY_DIRECTOR
References: