A Phase 3, Open-Label, Multicenter, Randomized Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents with Osteogenesis Imperfecta
Asato Keita
Amgen K.K.
Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo
+81-80-7217-8592
clinicaltrials_japan@amgen.com
Local Contact
Amgen K.K.
Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo
+81-80-7217-8592
clinicaltrials_japan@amgen.com
Not Recruiting
Feb. 22, 2024
April. 22, 2024
106
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1. 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.
2. 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.
3. 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).
- If familial, also must be autosomal dominant.
4. 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.
Disease Related
1. History of an electrophoresis pattern inconsistent with type I, III or IV OI.
2. 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.
3. History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation.
5age old over
17age old under
Both
Osteogenesis Imperfecta
Experimental: Romosozumab
Participants will receive romosozumab once a month (QM) for 12 months.
Intervention: Drug: Romosozumab
Active Comparator: Standard of Care Bisphosphonate
Participants will receive bisphosphonates per local standard of care treatment regimens, as determined by the investigator for 12 months.
Intervention: Drug: Bisphosphonate
1. Number of Clinical Fractures [Time Frame: 12 months]
Clinical fractures include clinical vertebral fractures and nonvertebral fractures.
2. Number of Any Fractures [Time Frame: 12 months]
Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures.
3. Change from Baseline in Lumbar Spine BMD Z-score at 12 Months, as assessed by DXA [Time Frame: Baseline and 12 months]
1. Change from Baseline in lumbar spine BMD Z-score at 6 months and 12 months, as assessed by DXA [Time Frame: Baseline, 6 months, and 12 months]
2. Change from Baseline in Total Hip BMD Z-score at 6 Months and at 12 Months, as assessed by DXA [Time Frame: Baseline, 6 months, and 12 months]
3. Change from Baseline in Femoral Neck BMD Z-score at 6 Months and at 12 Months, as assessed by DXA [Time Frame: Baseline, 6 months, and 12 months]
4. Number of Participants with Any Fractures [Time Frame: 12 months]
5. Number of Participants with Clinical Fractures [Time Frame: 12 months]
6. Number of Participants with New or Worsening Vertebral Fractures [Time Frame: 12 months]
7. Number of Participants with Nonvertebral Fractures [Time Frame: 12 months]
8, Number of Participants with Long Bone Fractures [Time Frame: 12 months]
9. Number of New or Worsening Vertebral Fractures [Time Frame: 12 months]
10. Number of Nonvertebral Fractures [Time Frame: 12 months]
11. Number of Long Bone Fractures [Time Frame: 12 months]
12. Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score [Time Frame: 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.
13. Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Score [Time Frame: 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.
14. Change from Baseline in the Wong-Baker Faces Pain Rating Scale [Time Frame: 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.
15. Serum Concentration of Romosozumab [Time Frame: Day 1 to Month 12]
16. Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months [Time Frame: 12 months]
Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.
17. Number of Participants who Experience TEAEs from Month 12 to Month 15 [Time Frame: 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.
18 Number of Participants with Anti-drug Antibodies (ADA) to Romosozumab [Time Frame: Up to 15 months]
19. Number of Participants who Experience TEAEs at 15 Months [Time Frame: 15 months]
Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.
20. Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull [Time Frame: Baseline and 6 months]
Measured in a subset of participants who receive cranial nerve computerized tomography (CT) scans.
21. Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull [Time Frame: Baseline and 12 months]
Measured in a subset of participants who receive cranial nerve CT scans.
