Clinical trial NCT03164928: Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With
Glucocorticoid-induced Osteoporosis
Keywords: Denosumab
Pediatric GIOP
Glucocorticoid-induced
Osteoporosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 24
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: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months
timeFrame: Baseline and 12 Months
Secondary outcomes:
measure: Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months
timeFrame: Baseline and 6, 18, 24, and 36 Months
measure: Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months
timeFrame: Baseline and 6, 12, 18, 24, and 36 Months
measure: Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months
timeFrame: Month 12, 24, and 36
measure: Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months
timeFrame: Month 12, 24, and 36
measure: Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months
timeFrame: Month 12, 24, and 36
measure: Change From Baseline in Child Health Questionnaire-Parent Form-50 (CHQ-PF-50) Physical Summary Score at 12, 24, and 36 Months
timeFrame: Baseline and month 12, 24, and 36
measure: Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Change From Baseline in Wong-Baker FACES Pain Rating Scale (WBFPRS) at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Change From Baseline in Growth Velocity Z-score (Height) at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Change From Baseline in Growth Velocity Z-score (Weight) at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Change From Baseline in Growth Velocity Z-score (BMI) at 12, 24, and 36 Months
timeFrame: Baseline and Month 12, 24, and 36
measure: Mean Serum Concentration of Denosumab
timeFrame: Day 1, Day 10, Day 30, Month 3, Month 6, Month 12, and Month 18
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: Wilmington
country: United States
facility: AI Dupont Hospital for Children
state: Delaware
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Childrens Hospital Discovery Clinic
state: Minnesota
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Nedlands
country: Australia
facility: Perth Childrens Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universtaire Saint Luc Universite Catholique de Louvain
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia EOOD
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: Medellin
country: Colombia
facility: Center for Clinical and Basic Research Colombia
state: Antioquia
city: Bogota
country: Colombia
facility: Solano y Terront Servicios Medicos Ltda - Unidad Integral de Endocrinologia Uniendo
state: Cundinamarca
city: Floridablanca
country: Colombia
facility: Foscal Internacional-Fundacion Oftalmologica de Santander
state: Santander
city: Hyderabad
country: India
facility: Gandhi Medical College
state: Andhra Pradesh
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Belagavi
country: India
facility: KLES Dr Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Meyer
city: Milan
country: Italy
facility: Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Umberto I
city: Ciudad de Mexico
country: Mexico
facility: RM Pharma Specialists SA de CV
city: Brena
country: Peru
facility: Instituto Nacional de Salud del Nino
state: Lima
city: Arequipa
country: Peru
facility: Centro Especializado de Enfermedades Neoplasicas
city: Callao
country: Peru
facility: Hospital Nacional Alberto Sabogal Sologuren
city: Lima
country: Peru
facility: Clinica Angloamericana
city: Lima
country: Peru
facility: Centro de Investigacion Ricardo Palma
city: Moscow
country: Russian Federation
facility: FSAI Scientific Center of Childrens Health of MoH of the RF
city: Moscow
country: Russian Federation
facility: SBEI of HPE First Moscow state medical university na I M Sechenov of MoH of Russian Federation
city: Novosibirsk
country: Russian Federation
facility: SBHI of Novosibirsk region City Pediatric Clinical Hospital of Emergency Care
city: Saint Petersburg
country: Russian Federation
facility: LLC Medical Technologies
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi
city: Erzurum
country: Turkey
facility: Ataturk Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara Universitesi Pendik Egitim Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Dnipro
country: Ukraine
facility: CI Dnipropetrovsk Regional Children Clinical Hospital of Dnipropetrovsk Regional Council
city: Kharkiv
country: Ukraine
facility: Communal Institution of Healthcare Kharkiv City Clinical Children Hospital 16
city: Kyiv
country: Ukraine
facility: National Childrens Specialized Hospital OHMATDYT
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: