Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis

NCT03164928 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 201404442016-003083-39
• Study Type: interventional
• Target: 24
• Locations: 13 countries
• Sites: 38

Brief Summary

To evaluate the effect of denosumab on lumbar spine bone mineral density (BMD) Z-score as assessed by dual-energy X-ray absorptiometry (DXA) at 12 months in children 5 to 17 year of age with Glucocorticoid (GC)-induced osteoporosis (GiOP).

Conditions

Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With; Glucocorticoid-induced Osteoporosis

Keywords

Denosumab; Pediatric GIOP; Glucocorticoid-induced; Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months

  Lumbar spine BMD was assessed by DXA and analyzed by analysis of covariance (ANCOVA) including treatment (denosumab vs placebo), baseline age, and baseline BMD z-score. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify lumbar spine BMD improvement.

  Baseline and 12 Months

Secondary Outcomes (13)

• Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months

  Baseline and 6, 18, 24, and 36 Months

• Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months

  Baseline and 6, 12, 18, 24, and 36 Months

• Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months

  Month 12, 24, and 36

• Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months

  Month 12, 24, and 36

• Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months

  Month 12, 24, and 36

Study Arms (2)

Placebo

OTHER

SC Q6M placebo

Other: Placebo

Denosumab

EXPERIMENTAL

1 mg/kg BW (up to a maximum of 60 mg) SC Q6M

Drug: Denosumab

Interventions

Denosumab DRUG

1mg/kg BW (up to a maximum of 60 mg) SC Q6M

Denosumab

Placebo OTHER

SC Q6M placebo

Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female subjects, age 5 to 17 years, inclusive, at the time of informed consent.
• Clinical diagnosis of GiOP as defined by the following (and consistent with the International Society for Clinical Densitometry definition of osteoporosis in children and adolescents \[Bishop et al, 2014\])
• A confirmed diagnosis of non-malignant condition(s) requiring treatment with systemic GC (including, but not limited to, chronic rheumatologic, gastrointestinal, neurologic, respiratory, and/or nephrological conditions)
• Subjects who are on systemic GC only as replacement therapy for adrenal insufficiency are not eligible for the study - Treatment with systemic GC (intravenous or oral) of any duration for the underlying non-malignant condition(s) within the 12 months prior to screening
• Evidence of at least 1 vertebral compression fracture of Genant grade 1 or higher, as assessed by the central imaging vendor on lateral spine X-rays performed at screening or within 2 months prior to screening; OR, in the absence of vertebral compression fractures, presence of both clinically significant fracture history (ie, ≥ 2 long-bone fractures by age 10 years or ≥ 3 long-bone fractures at any age up to 17 years) and lumbar spine BMD Z-score ≤ -2.0, as assessed by the central imaging vendor.
• Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated
• A confirmed diagnosis of non-malignant condition(s) requiring treatment with systemic GC (including, but not limited to, chronic rheumatologic, gastrointestinal, neurologic, respiratory, and/or nephrological conditions)
• Subjects who are on systemic GC only as replacement therapy for adrenal insufficiency are not eligible for the study
• Treatment with systemic GC (intravenous or oral) of any duration for the underlying non malignant condition(s) within the 12 months prior to screening
• Prepubertal children should be expected to require significant GC use during the study, per investigator opinion

You may not qualify if:

• Current hyperthyroidism (unless well controlled on stable antithyroid therapy)
• Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy)
• History of hyperparathyroidism
• Current hypoparathyroidism
• Duchenne muscular dystrophy with symptomatic cardiac abnormality
• Current malabsorption
• Active infection or history of infections
• History of malignancy
• Any causes of primary or secondary osteoporosis (other than GC use), or previous exposure to non-GC medications, which the investigator considers to have been a major factor contributing to the patient's fracture(s)
• Current adrenal insufficiency as the sole indication for GC therapy
• Duchenne muscular dystrophy with symptomatic cardiac abnormality
• Current malabsorption (in children with serum albumin -lower limit of normal \[LLN\], malabsorption should be clinically ruled out by the investigator to confirm eligibility)
• Known intolerance to calcium or vitamin D supplements
• Active infection or history of infections, defined as follows:
• Any active infection for which systemic anti-infectives were used within 4 weeks prior to screening

Sponsors & Collaborators

• Amgen: lead

Study Sites (38)

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

AI Dupont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Minnesota Masonic Childrens Hospital Discovery Clinic

Minneapolis, Minnesota, 55454, United States

Location

Metrohealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

Perth Childrens Hospital

Nedlands, Western Australia, 6909, Australia

Location

Cliniques Universtaire Saint Luc Universite Catholique de Louvain

Brussels, 1200, Belgium

Location

Medical Centre Synexus Sofia EOOD

Sofia, 1784, Bulgaria

Location

Childrens Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Centre Hospitalier Universitaire Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Center for Clinical and Basic Research Colombia

Medellín, Antioquia, 050021, Colombia

Location

Solano y Terront Servicios Medicos Ltda - Unidad Integral de Endocrinologia Uniendo

Bogota, Cundinamarca, 110221, Colombia

Location

Foscal Internacional-Fundacion Oftalmologica de Santander

Floridablanca, Santander Department, 681004, Colombia

Location

Gandhi Medical College

Hyderabad, Andhra Pradesh, 500 025, India

Location

KLES Dr Prabhakar Kore Hospital and Medical Research Centre

Belagavi, Karnataka, 590010, India

Location

Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, 110 022, India

Location

Christian Medical College

Vellore, Tamil Nadu, 632 004, India

Location

Azienda Ospedaliera Universitaria Meyer

Florence, 50139, Italy

Location

Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico

Milan, 20145, Italy

Location

Azienda Ospedaliera Policlinico Umberto I

Roma, 00161, Italy

Location

RM Pharma Specialists SA de CV

Mexico City, 03100, Mexico

Location

Instituto Nacional de Salud del Nino

Breña, Lima region, Lima 5, Peru

Location

Centro Especializado de Enfermedades Neoplasicas

Arequipa, 040001, Peru

Location

Hospital Nacional Alberto Sabogal Sologuren

Callao, Callao 2, Peru

Location

Clinica Angloamericana

Lima, Lima 27, Peru

Location

Centro de Investigacion Ricardo Palma

Lima, Lima27, Peru

Location

FSAI Scientific Center of Childrens Health of MoH of the RF

Moscow, 119991, Russia

Location

SBEI of HPE First Moscow state medical university na I M Sechenov of MoH of Russian Federation

Moscow, 119991, Russia

Location

SBHI of Novosibirsk region City Pediatric Clinical Hospital of Emergency Care

Novosibirsk, 630007, Russia

Location

LLC Medical Technologies

Saint Petersburg, 191025, Russia

Location

Ankara Universitesi Tip Fakultesi

Ankara, 06590, Turkey (Türkiye)

Location

Ataturk Universitesi Tip Fakultesi

Erzurum, 25240, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Egitim Arastirma Hastanesi

Istanbul, 34890, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35100, Turkey (Türkiye)

Location

CI Dnipropetrovsk Regional Children Clinical Hospital of Dnipropetrovsk Regional Council

Dnipro, 49100, Ukraine

Location

Communal Institution of Healthcare Kharkiv City Clinical Children Hospital 16

Kharkiv, 61075, Ukraine

Location

National Childrens Specialized Hospital OHMATDYT

Kyiv, 01025, Ukraine

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 24, 2017
• Study Start: May 7, 2018
• Primary Completion: December 13, 2021
• Study Completion: December 20, 2023
• Last Updated: July 19, 2024
• Results First Posted: July 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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 link below.

Locations

TU (4); UA (3); US (6); BU (1); IN (4); CO (3); AU (1); IT (3); BE (1); CA (2); PE (5); RU (4); ME (1)