Clinical trial NCT05972551: Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Osteogenesis Imperfecta
Keywords: Osteogenesis Imperfecta
Romosozumab
EVENITY®
Bisphosphonates
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-08-02
Enrollment: 106
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Clinical Fractures
timeFrame: 12 months
measure: Number of Any Fractures
timeFrame: 12 months
measure: Change from Baseline to 12 Months in Lumbar Spine BMD Z-score
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Change from Baseline in Lumbar Spine BMD Z-score at 6 Months and at 12 Months
timeFrame: Baseline, 6 months, and 12 months
measure: Change from Baseline in Total Hip BMD Z-score at 6 Months and at 12 Months
timeFrame: Baseline, 6 months, and 12 months
measure: Change from Baseline in Femoral Neck BMD Z-score at 6 Months and at 12 Months
timeFrame: Baseline, 6 months, and 12 months
measure: Number of Participants with Any Fractures
timeFrame: 12 months
measure: Number of Participants with Clinical Fractures
timeFrame: 12 months
measure: Number of Participants with New or Worsening Vertebral Fractures
timeFrame: 12 months
measure: Number of Participants with Nonvertebral Fractures
timeFrame: 12 months
measure: Number of Participants with Long Bone Fractures
timeFrame: 12 months
measure: Number of New or Worsening Vertebral Fractures
timeFrame: 12 months
measure: Number of Nonvertebral Fractures
timeFrame: 12 months
measure: Number of Long Bone Fractures
timeFrame: 12 months
measure: Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score
timeFrame: Baseline and 12 months
measure: Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Score
timeFrame: Baseline and 12 months
measure: Change from Baseline in the Wong-Baker Faces Pain Rating Scale
timeFrame: Baseline and 12 months
measure: Serum Concentration of Romosozumab
timeFrame: Day 1 to Month 12
measure: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months
timeFrame: 12 months
measure: Number of Participants who Experience TEAEs from Month 12 to Month 15
timeFrame: Month 12 to Month 15
measure: Number of Participants with Anti-drug Antibodies (ADA) to Romosozumab
timeFrame: Up to 15 months
measure: Number of Participants who Experience TEAEs at 15 Months
timeFrame: 15 months
measure: Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
timeFrame: Baseline and 6 months
measure: Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Childrens Center
state: Minnesota
city: Saint Paul
country: United States
facility: Gillette Childrens Hospital and Clinic Saint Paul
state: Minnesota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Clayton
country: Australia
facility: Monash Childrens Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perth Childrens Hospital
state: Western Australia
city: Linz
country: Austria
facility: Kepler Universitaetsklinikum GmbH
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte Justine
state: Quebec
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin
city: Paris Cedex 15
country: France
facility: Hopital Necker Enfants Malades
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Okayama-shi
country: Japan
facility: Okayama Saiseikai Outpatient Center Hospital
state: Okayama
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Izumi-shi
country: Japan
facility: Osaka Womens and Childrens Hospital
state: Osaka
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and Development
state: Tokyo
city: Lodz
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny UMeds
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Tychy
country: Poland
facility: Szpital Miejski w Tychach Spolka z ograniczona odpowiedzialnoscia
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Esplugues De Llorbregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Cataluña
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
state: Madrid
city: Baracaldo
country: Spain
facility: Hospital de Cruces
state: País Vasco
city: Madrid
country: Spain
facility: Hospital Universitario Infantil Niño Jesus
city: Basel
country: Switzerland
facility: Universitaets-Kinderspital beider Basel
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Ankara
country: Turkey
facility: Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
city: Istanbul
country: Turkey
facility: Marmara Universitesi Tip Fakultesi Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: Trabzon
country: Turkey
facility: Karadeniz Teknik Universitesi Hastanesi
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: