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

Glucocorticoid-induced Osteoporosis Clinical Trial

Official title:

A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03164928
• Other study ID #: 20140444
• Secondary ID: 2016-003083-39
• Status: Completed
• Phase: Phase 3
• Start date: May 7, 2018
• Est. completion date: December 20, 2023

Study information

• Verified date: January 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 20, 2023
• Est. primary completion date: December 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion criteria will include the following:

• 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

• Serious infection, defined as requiring hospitalization or intravenous anti infectives within 8 weeks prior to screening

• Recurrent or chronic infection or other active infection that, in the opinion of the investigator, might compromise the safety of the subject

Related Conditions & MeSH terms

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

Intervention

Drug:
• Denosumab
1mg/kg BW (up to a maximum of 60 mg) SC Q6M

Other:
• Placebo
SC Q6M placebo

Locations

Country	Name	City	State
Australia	Perth Childrens Hospital	Nedlands	Western Australia
Belgium	Cliniques Universtaire Saint Luc Universite Catholique de Louvain	Bruxelles
Bulgaria	Medical Centre Synexus Sofia EOOD	Sofia
Canada	Centre Hospitalier Universitaire Sainte Justine	Montreal	Quebec
Canada	Childrens Hospital of Eastern Ontario	Ottawa	Ontario
Colombia	Solano y Terront Servicios Medicos Ltda - Unidad Integral de Endocrinologia Uniendo	Bogota	Cundinamarca
Colombia	Foscal Internacional-Fundacion Oftalmologica de Santander	Floridablanca	Santander
Colombia	Center for Clinical and Basic Research Colombia	Medellin	Antioquia
India	KLES Dr Prabhakar Kore Hospital and Medical Research Centre	Belagavi	Karnataka
India	Gandhi Medical College	Hyderabad	Andhra Pradesh
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Christian Medical College	Vellore	Tamil Nadu
Italy	Azienda Ospedaliera Universitaria Meyer	Firenze
Italy	Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico	Milan
Italy	Azienda Ospedaliera Policlinico Umberto I	Roma
Mexico	RM Pharma Specialists SA de CV	Ciudad de Mexico
Peru	Centro Especializado de Enfermedades Neoplasicas	Arequipa
Peru	Instituto Nacional de Salud del Nino	Brena	Lima
Peru	Hospital Nacional Alberto Sabogal Sologuren	Callao
Peru	Centro de Investigacion Ricardo Palma	Lima
Peru	Clinica Angloamericana	Lima
Russian Federation	FSAI Scientific Center of Childrens Health of MoH of the RF	Moscow
Russian Federation	SBEI of HPE First Moscow state medical university na I M Sechenov of MoH of Russian Federation	Moscow
Russian Federation	SBHI of Novosibirsk region City Pediatric Clinical Hospital of Emergency Care	Novosibirsk
Russian Federation	LLC Medical Technologies	Saint Petersburg
Turkey	Ankara Universitesi Tip Fakultesi	Ankara
Turkey	Ataturk Universitesi Tip Fakultesi	Erzurum
Turkey	Marmara Universitesi Pendik Egitim Arastirma Hastanesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Ukraine	CI Dnipropetrovsk Regional Children Clinical Hospital of Dnipropetrovsk Regional Council	Dnipro
Ukraine	Communal Institution of Healthcare Kharkiv City Clinical Children Hospital 16	Kharkiv
Ukraine	National Childrens Specialized Hospital OHMATDYT	Kyiv
United States	Metrohealth Medical Center	Cleveland	Ohio
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	University of Minnesota Masonic Childrens Hospital Discovery Clinic	Minneapolis	Minnesota
United States	AI Dupont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Colombia,  India,  Italy,  Mexico,  Peru,  Russian Federation,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 12 months	Change from baseline in lumbar spine BMD Z-score (bone mineral density) as assessed by DXA (dual-energy X-ray absorptiometry) at 12 months.	12 months
Secondary	Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 6, 18, 24, and 36 months.	Change from baseline in lumbar spine BMD Z-score (bone mineral density) as assessed by DXA (dual-energy X-ray absorptiometry) at 6, 18, 24, and 36 months.	6, 18, 24, and 36 months
Secondary	Change from baseline in proximal femur BMD Z-score as assessed by DXA at 6, 12, 18, 24, and 36 months.	Change from baseline in proximal femur BMD Z-score (bone mineral density) as assessed by DXA (dual-energy X-ray absorptiometry) at 6, 12, 18, 24, and 36 months.	6, 12, 18, 24, and 36 months
Secondary	Number of participants with X-ray confirmed long-bone fractures and new and worsening vertebral fractures during 12, 24, and 36 months	Number of participants with X-ray confirmed long-bone fractures and new and worsening vertebral fractures during 12, 24, and 36 months compared to pre-treatment	12, 24, and 36 months
Secondary	Number of participants with improving vertebral fractures at 12, 24, and 36 months compared to baseline	Number of participants with improving vertebral fractures at 12, 24, and 36 months compared to pre-treatment (overall, among subjects with clinical fracture reduction, and among subjects with clinical fracture increase)	12, 24, and 36 months
Secondary	Number of participants with new and worsening vertebral and nonvertebral fractures during 12, 24, and 36 months compared to pre-treatment.	Number of subjects with pre-treatment, post-treatment, and post-withdrawal vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pre-treatment.	12, 24, and 36 months
Secondary	Change from baseline in CHQ-PF-50 Physical Summary Score at 12, 24, and 36 months.	Change from baseline in CHQ-PF-50 (Childhood Health Questionnaire - Parent Form-50) Physical Summary Score at 12, 24, and 36 months	12, 24, 36 months
Secondary	Change from baseline in CHQ-PF-50 Psychological Summary Score at 12, 24, and 36 months	Change from baseline in CHQ-PF-50 (Childhood Health Questionnaire - Parent Form-50) Psychological Summary Score at 12, 24, and 36 months	12, 24, and 36 months
Secondary	Change from baseline in CHAQ Disability Index Score at 12, 24, and 36 months	Change from baseline in CHAQ (Childhood Health Assessment Questionnaire) Disability Index Score at 12, 24, and 36 months	12, 24, and 36 months
Secondary	Change from baseline WBFPRS at 12, 24, and 36 months	Change from baseline WBFPRS (Wong-Baker Faces Pain Rating Scale) at 12, 24, and 36 months	12, 24, and 36 months
Secondary	Change from baseline in growth velocity, determined by calculating age-adjusted Z-scores for height, weight, and Body Mass Index at 12, 24, and 36 months	Change from baseline in growth velocity, determined by calculating age-adjusted Z-scores for height, weight, and Body Mass Index at 12, 24, and 36 months	12, 24, and 36 months
Secondary	Serum concentration of denosumab on Days 1, 10, and 30, and at 3, 6, 12, and 18 months	Serum concentration of denosumab on Days 1, 10, and 30, and at 3, 6, 12, and 18 months	Days 1, 10, and 30, and at 3, 6, 12, and 18 months

External Links

•   AmgenTrials clinical trials website