Osteogenesis Imperfecta
Conditions
Keywords
Osteogenesis Imperfecta, Romosozumab, EVENITY®, Bisphosphonates
Brief summary
The primary objective of this study is to evaluate the effect of romosozumab treatment for 12-months compared with bisphosphonate(s) on the number of clinical fractures at 12-months; the number of any fractures at 12-months and change in lumbar spine bone mineral density (BMD) Z-score at 6-months.
Interventions
DRUGRomosozumab
Subcutaneous (SC) injection
DRUGBisphosphonate
Administration determined by investigator according to the local standard of care
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures. OR * Participant's legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the participant has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated. * Ambulatory male and female children and adolescents, age 5 to \<18 years, including ambulatory with assistance as defined in the pediatric osteogenesis imperfecta (OI) population. * Clinical diagnosis of OI, defined as clinical history consistent with type I, III, or IV OI as determined by presence of expected phenotype (examples include: facial shape, voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture pattern) and lack of additional features unrelated to type I, III, or IV OI (eg, blindness, mental retardation, neuropathy, and craniosynostosis). o If familial, also must be autosomal dominant. * Meets at least one of the following: * 3 or more fractures within the previous 2 years, or * 1 or more nonvertebral fracture(s) within the previous 2 years and at least 1 prevalent vertebral fracture, or * 2 or more prevalent vertebral fractures.
Exclusion criteria
Disease Related * History of an electrophoresis pattern inconsistent with type I, III or IV OI. * History of known mutation in a gene other than collagen type I alpha 1/collagen type I alpha 2 (COL1A1/COL1A2) causing OI or other metabolic bone disease. * History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinical Fractures | 12 months | Clinical fractures include clinical vertebral fractures and nonvertebral fractures. |
| Number of Any Fractures | 12 months | Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures. |
| Change from Baseline in Lumbar Spine BMD Z-score at 12 Months, as assessed by DXA | Baseline and 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in lumbar spine BMD Z-score at 6 months and 12 months, as assessed by DXA | Baseline, 6 months, and 12 months | — |
| Change from Baseline in Total Hip BMD Z-score at 6 Months and at 12 Months, as assessed by DXA | Baseline, 6 months, and 12 months | — |
| Change from Baseline in Femoral Neck BMD Z-score at 6 Months and at 12 Months, as assessed by DXA | Baseline, 6 months, and 12 months | — |
| Number of Participants with Any Fractures | 12 months | — |
| Number of Participants with Clinical Fractures | 12 months | — |
| Number of Participants with New or Worsening Vertebral Fractures | 12 months | — |
| Number of Participants with Nonvertebral Fractures | 12 months | — |
| Number of Participants with Long Bone Fractures | 12 months | — |
| Number of New or Worsening Vertebral Fractures | 12 months | — |
| Number of Nonvertebral Fractures | 12 months | — |
| Number of Long Bone Fractures | 12 months | — |
| Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score | Baseline and 12 months | The CHQ-PF-50 measures how a child's condition affects their ability to function in daily life. The CHQ-PF-50 measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations - emotional/behavioral, parent impact - time, parent impact - emotion, self-esteem, mental health, behavior, family cohesion, change in health. Each item is rated on a scale from "without any difficulty" to "unable to do". Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states. |
| Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Score | Baseline and 12 months | The CHAQ measures how a child's condition affects their ability to function in daily life. The CHAQ measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations emotional/behavioral, self-esteem, mental health, behavior, family cohesion, change in health. Each item is rated on a scale from "without any difficulty" to "unable to do". Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states. |
| Change from Baseline in the Wong-Baker Faces Pain Rating Scale | Baseline and 12 months | The Wong-Baker Faces Pain Rating Scale is a horizontal pain scale that consists of six hand-drawn faces that range from a smiling "no hurt" face with a score of 0 to a crying "hurts worst" face with a score of 10. Greater change from baseline scores indicate greater pain experienced by the participant. |
| Serum Concentration of Romosozumab | Day 1 to Month 12 | — |
| Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months | 12 months | Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE. |
| Number of Participants who Experience TEAEs from Month 12 to Month 15 | Month 12 to Month 15 | Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE. |
| Number of Participants with Anti-drug Antibodies (ADA) to Romosozumab | Up to 15 months | — |
| Number of Participants who Experience TEAEs at 15 Months | 15 months | Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE. |
| Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull | Baseline and 6 months | Measured in a subset of participants who receive cranial nerve computerized tomography (CT) scans. |
| Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull | Baseline and 12 months | Measured in a subset of participants who receive cranial nerve CT scans. |
Countries
Australia, Austria, Belgium, Canada, China, France, Germany, Hungary, Italy, Japan, Poland, Saudi Arabia, Slovakia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed