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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Osteogenesis Imperfecta
• Intervention / Treatment: Drug: Romosozumab; Drug: Bisphosphonate

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Childrens Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6909
      • Perth Childrens Hospital
• Austria
  • Linz, Austria, 4020
    • Kepler Universitaetsklinikum GmbH
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Childrens Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte Justine
• China
  • Shanghai, China, 200233
    • Shanghai Sixth Peoples Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
  • Guangdong
    • Shenzhen, Guangdong, China, 518053
      • The University of Hong Kong-Shenzhen Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital , Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Childrens Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • West China Hospital Sichuan University
• France
  • Bordeaux, France, 33076
    • Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin
  • Lille, France, 59037
    • Centre Hospitalier Régional Universitaire de Lille
  • Paris, France, 75743
    • Hopital Necker Enfants Malades
• Germany
  • Cologne, Germany, 50937
    • Universitaetsklinikum Koeln
  • Würzburg, Germany, 97074
    • Universitaetsklinikum Wuerzburg
• Hungary
  • Budapest, Hungary, 1094
    • Semmelweis Egyetem
• Italy
  • Genova, Italy, 16147
    • IRCCS Istituto Giannina Gaslini
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
• Japan
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 700-8558
      • Okayama University Hospital
    • Okayama, Okayama-ken, Japan, 700-0013
      • Okayama Saiseikai Outpatient Center Hospital
  • Osaka
    • Izumi-shi, Osaka, Japan, 594-1101
      • Osaka Womens and Childrens Hospital
  • Tokyo
    • Fuchu-shi, Tokyo, Japan, 183-8561
      • Tokyo Metropolitan Children's Medical Center
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development
  • Tottori
    • Yonago-shi, Tottori, Japan, 683-8504
      • Tottori University Hospital
• Poland
  • Krakow, Poland, 31-530
    • Centermed Krakow Sp zoo
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
  • Lodz, Poland, 91-738
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny UMeds
  • Rzeszów, Poland, 35-326
    • Centrum Medyczne Medyk Spolka z Ograniczona Odpowiedzialnoscia Spolka Komandytowa
  • Tychy, Poland, 43-100
    • Szpital Miejski w Tychach Spolka z ograniczona odpowiedzialnoscia
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11564
    • King Faisal Specialist Hospital and Research Centre
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Narodny ustav detskych chorob
• Spain
  • Madrid, Spain, 28009
    • Hospital Universitario Infantil Nino Jesus
  • Basque Country
    • Barakaldo, Basque Country, Spain, 48903
      • Hospital de Cruces
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall D Hebron
    • Esplugues de Llobregat, Catalonia, Spain, 08950
      • Hospital Sant Joan de Déu
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Hospital Universitario de Getafe
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Hospital Universitari i Politecnic La Fe
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaets-Kinderspital beider Basel
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06500
    • Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
  • Istanbul, Turkey (Türkiye), 34890
    • Marmara Universitesi Tip Fakultesi Hastanesi
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Tip Fakultesi Hastanesi
  • Trabzon, Turkey (Türkiye), 61080
    • Karadeniz Teknik Universitesi Tip Fakultesi
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Childrens Hospital
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Childrens Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Childrens Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles Interventional Clinical Trials
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Hospital for Children
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Childrens Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Kennedy Krieger Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Childrens Center
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Childrens Hospital and Clinic Saint Paul
  • Tennessee
    • Nashville, Tennessee, United States, 37212-3157
      • Vanderbilt University Medical Center
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romosozumab; Participants will receive romosozumab once a month (QM) for 12 months.	Drug: Romosozumab; Subcutaneous (SC) injection; Other Names: EVENITY®
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.	Drug: Bisphosphonate; Administration determined by investigator according to the local standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Clinical Fractures	Clinical fractures include clinical vertebral fractures and nonvertebral fractures.	12 months
Number of Any Fractures	Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures.	12 months
Change from Baseline in Lumbar Spine BMD Z-score at 12 Months, as assessed by DXA		Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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	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.	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.	Baseline and 12 months
Serum Concentration of Romosozumab		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.	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.	Month 12 to Month 15
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.	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.	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.	Baseline and 12 months
Number of Participants with Long Bone Fractures		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.	Baseline and 12 months
Number of Participants with Anti-drug Antibodies (ADA) to Romosozumab		Up to 15 months
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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): May 4, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Bisphosphonates; Osteogenesis Imperfecta; Romosozumab; EVENITY®
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Osteogenesis Imperfecta; Organic Chemicals; Organophosphorus Compounds; Organophosphonates; Diphosphonates; romosozumab
• Other Study ID Numbers: 20200105; 2023-503294-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No