Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta

Phase 3RecruitingNCT05972551

Amgen106 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

106

Conditions

Osteogenesis Imperfecta

Interventions

RomosozumabDRUG

Subcutaneous (SC) injection

BisphosphonateDRUG

Administration determined by investigator according to the local standard of care

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (65)

Outcomes

Primary Outcomes

Number of Clinical Fractures

Clinical fractures include clinical vertebral fractures and nonvertebral fractures.

Time frame: 12 months

Number of Any Fractures

Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures.

Time frame: 12 months

Change from Baseline in Lumbar Spine BMD Z-score at 12 Months, as assessed by DXA

Time frame: Baseline and 12 months

Secondary Outcomes

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

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

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

Number of Participants with Any Fractures

Time frame: 12 months

Number of Participants with Clinical Fractures

Time frame: 12 months

Number of Participants with New or Worsening Vertebral Fractures

Time frame: 12 months

Number of Participants with Nonvertebral Fractures

Central Contacts

Amgen Call Center

CONTACT

866-572-6436 medinfo@amgen.com

Data from ClinicalTrials.gov

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Childrens Hospital of Alabama

Birmingham, Alabama, United States

TERMINATED

Phoenix Childrens Hospital

Phoenix, Arizona, United States

RECRUITING

University of California, Los Angeles Interventional Clinical Trials

Los Angeles, California, United States

RECRUITING

Nemours Hospital for Children

Wilmington, Delaware, United States

RECRUITING

Nemours Childrens Hospital

Orlando, Florida, United States

RECRUITING

University of South Florida - Carol and Frank Morsani Center for Advanced Health Care

Tampa, Florida, United States

RECRUITING

Emory University

Atlanta, Georgia, United States

RECRUITING

Indiana University

Indianapolis, Indiana, United States

RECRUITING

Kennedy Krieger Institute

Baltimore, Maryland, United States

RECRUITING

Boston Childrens Hospital

Boston, Massachusetts, United States

RECRUITING

...and 55 more locations

Time frame: 12 months

Number of Participants with Long Bone Fractures

Time frame: 12 months

Number of New or Worsening Vertebral Fractures

Time frame: 12 months

Number of Nonvertebral Fractures

Time frame: 12 months

Number of Long Bone Fractures

Time frame: 12 months

Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score

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.

Time frame: Baseline and 12 months

Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Score

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.

Time frame: Baseline and 12 months

Change from Baseline in the Wong-Baker Faces Pain Rating Scale

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.

Time frame: Baseline and 12 months

Serum Concentration of Romosozumab

Time frame: Day 1 to Month 12

Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months

Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.

Time frame: 12 months

Number of Participants who Experience TEAEs from 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.

Time frame: Month 12 to Month 15

Number of Participants with Anti-drug Antibodies (ADA) to Romosozumab

Time frame: Up to 15 months

Number of Participants who Experience TEAEs at 15 Months

Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.

Time frame: 15 months

Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull

Measured in a subset of participants who receive cranial nerve computerized tomography (CT) scans.

Time frame: Baseline and 6 months

Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull

Measured in a subset of participants who receive cranial nerve CT scans.

Time frame: Baseline and 12 months