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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03164928




Registration number
NCT03164928
Ethics application status
Date submitted
8/05/2017
Date registered
24/05/2017
Date last updated
28/08/2020

Titles & IDs
Public title
Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis
Scientific 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
Secondary ID [1] 0 0
2016-003083-39
Secondary ID [2] 0 0
20140444
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With 0 0
Glucocorticoid-induced Osteoporosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Denosumab
Other interventions - Placebo

Other: Placebo - SC Q6M placebo

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


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

Other interventions: Placebo
SC Q6M placebo

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
6 - 36 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
6 - 36 months
Secondary outcome [3] 0 0
Subject incidence of X-ray confirmed long-bone fractures and new and worsening vertebral fractures at 12, 24, and 36 months compared to pre-treatment - Subject incidence of X-ray confirmed long-bone fractures and new and worsening vertebral fractures at 12, 24, and 36 months compared to pre-treatment
Timepoint [3] 0 0
12, 24, and 36 months
Secondary outcome [4] 0 0
Subject incidence of improving vertebral fractures at 12, 24, and 36 months compared to pretreatment - Subject incidence of improving vertebral fractures at 12, 24, and 36 months compared to pretreatment (overall, among subjects with clinical fracture reduction, and among subjects with clinical fracture increase)
Timepoint [4] 0 0
12, 24, and 36 months
Secondary outcome [5] 0 0
Subject incidence of vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pretreatment. - Number of subjects with vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pretreatment.
Timepoint [5] 0 0
6 - 36 months
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
6 - 36 months
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
12, 24, and 36 months
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
12, 24, and 36 months
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
12, 24, and 36 months
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
12, 24, and 36 months
Secondary outcome [11] 0 0
Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, and 18 months - Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, and 18 months
Timepoint [11] 0 0
Days 1, 10, and 30, and months 3, 6, 12, and 18.

Eligibility
Key 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

- 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

- Prepubertal children should be expected to require significant GC use during the
study, per investigator opinion
Minimum age
5 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
6909 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Sofia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Colombia
State/province [9] 0 0
Antioquia
Country [10] 0 0
Colombia
State/province [10] 0 0
Cundinamarca
Country [11] 0 0
Colombia
State/province [11] 0 0
Santander
Country [12] 0 0
India
State/province [12] 0 0
Andhra Pradesh
Country [13] 0 0
India
State/province [13] 0 0
Delhi
Country [14] 0 0
India
State/province [14] 0 0
Karnataka
Country [15] 0 0
India
State/province [15] 0 0
Tamil Nadu
Country [16] 0 0
Italy
State/province [16] 0 0
Firenze
Country [17] 0 0
Italy
State/province [17] 0 0
Milan
Country [18] 0 0
Italy
State/province [18] 0 0
Roma
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Mexico
State/province [20] 0 0
Distrito Federal
Country [21] 0 0
Peru
State/province [21] 0 0
Lima
Country [22] 0 0
Peru
State/province [22] 0 0
Arequipa
Country [23] 0 0
Peru
State/province [23] 0 0
Callao
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Moscow
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Novosibirsk
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Saint Petersburg
Country [27] 0 0
Turkey
State/province [27] 0 0
Ankara
Country [28] 0 0
Turkey
State/province [28] 0 0
Erzurum
Country [29] 0 0
Turkey
State/province [29] 0 0
Istanbul
Country [30] 0 0
Turkey
State/province [30] 0 0
Izmir
Country [31] 0 0
Ukraine
State/province [31] 0 0
Dnipro
Country [32] 0 0
Ukraine
State/province [32] 0 0
Kharkiv
Country [33] 0 0
Ukraine
State/province [33] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03164928
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03164928