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

Phase 3
Recruiting
Conditions
Interventions
Registration Number
NCT05972551
Lead Sponsor
Amgen
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
106
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.
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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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard of Care BisphosphonateBisphosphonateParticipants will receive bisphosphonates per local standard of care treatment regimens, as determined by the investigator for 12 months.
RomosozumabRomosozumabParticipants will receive romosozumab once a month (QM) for 12 months.
Primary Outcome Measures
NameTimeMethod
Number of Clinical Fractures12 months

Clinical fractures include clinical vertebral fractures and nonvertebral fractures.

Number of Any Fractures12 months

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

Change from Baseline to 12 Months in Lumbar Spine BMD Z-scoreBaseline and 12 months
Secondary Outcome Measures
NameTimeMethod
Change from Baseline in Lumbar Spine BMD Z-score at 6 Months and at 12 MonthsBaseline, 6 months, and 12 months
Change from Baseline in Total Hip BMD Z-score at 6 Months and at 12 MonthsBaseline, 6 months, and 12 months
Change from Baseline in Femoral Neck BMD Z-score at 6 Months and at 12 MonthsBaseline, 6 months, and 12 months
Number of Participants with Any Fractures12 months
Number of Participants with Clinical Fractures12 months
Number of Participants with New or Worsening Vertebral Fractures12 months
Number of Participants with Nonvertebral Fractures12 months
Number of Participants with Long Bone Fractures12 months
Number of New or Worsening Vertebral Fractures12 months
Number of Nonvertebral Fractures12 months
Number of Long Bone Fractures12 months
Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary ScoreBaseline 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 ...

Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability ScoreBaseline 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, fam...

Change from Baseline in the Wong-Baker Faces Pain Rating ScaleBaseline 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 RomosozumabDay 1 to Month 12
Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months12 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 15Month 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 RomosozumabUp to 15 months
Number of Participants who Experience TEAEs at 15 Months15 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 SkullBaseline 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 SkullBaseline and 12 months

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

Trial Locations

Locations (35)

Okayama University Hospital

🇯🇵

Okayama-shi, Okayama, Japan

Osaka Womens and Childrens Hospital

🇯🇵

Izumi-shi, Osaka, Japan

National Center for Child Health and Development

🇯🇵

Setagaya-ku, Tokyo, Japan

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny UMeds

🇵🇱

Lodz, Poland

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

Szpital Miejski w Tychach Spolka z ograniczona odpowiedzialnoscia

🇵🇱

Tychy, Poland

Narodny ustav detskych chorob

🇸🇰

Bratislava, Slovakia

Hospital Sant Joan de Deu

🇪🇸

Esplugues De Llorbregat, Cataluña, Spain

Hospital Universitario de Getafe

🇪🇸

Getafe, Madrid, Spain

Hospital de Cruces

🇪🇸

Baracaldo, País Vasco, Spain

Hospital Universitario Infantil Niño Jesus

🇪🇸

Madrid, Spain

Universitaets-Kinderspital beider Basel

🇨🇭

Basel, Switzerland

Centre Hospitalier Universitaire Vaudois

🇨🇭

Lausanne, Switzerland

Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi

🇹🇷

Ankara, Turkey

Marmara Universitesi Tip Fakultesi Hastanesi

🇹🇷

Istanbul, Turkey

Ege Universitesi Tip Fakultesi Hastanesi

🇹🇷

Izmir, Turkey

Karadeniz Teknik Universitesi Hastanesi

🇹🇷

Trabzon, Turkey

Queen Elizabeth University Hospital

🇬🇧

Glasgow, United Kingdom

Emory University

🇺🇸

Atlanta, Georgia, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Kennedy Krieger Institute

🇺🇸

Baltimore, Maryland, United States

Boston Childrens Hospital

🇺🇸

Boston, Massachusetts, United States

Mayo Clinic Childrens Center

🇺🇸

Rochester, Minnesota, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Monash Childrens Hospital

🇦🇺

Clayton, Victoria, Australia

Perth Childrens Hospital

🇦🇺

Nedlands, Western Australia, Australia

Kepler Universitaetsklinikum GmbH

🇦🇹

Linz, Austria

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

🇧🇪

Leuven, Belgium

Childrens Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

Centre Hospitalier Universitaire Sainte Justine

🇨🇦

Montreal, Quebec, Canada

Hopital Necker Enfants Malades

🇫🇷

Paris Cedex 15, France

Universitaetsklinikum Koeln

🇩🇪

Koeln, Germany

Universitaetsklinikum Wuerzburg

🇩🇪

Wuerzburg, Germany

Semmelweis Egyetem

🇭🇺

Budapest, Hungary

Okayama Saiseikai Outpatient Center Hospital

🇯🇵

Okayama-shi, Okayama, Japan

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