None listed
Conditions
Interventions
Subjects will be randomized in a 2:1 (active:placebo)
Treatment group 1: denosumab 1 mg/kg body weight (up to a maximum of 60 mg)
Subcutaneous every 6 months.
Daily supplements of calcium and vitamin D will be given to all subjects during the 24-month treatment period. Type of group
Treatment group 1: Denosumab 70mg/ml Solution for injection.
Dosage: denosumab 1 mg/kg body weight (up to a maximum of 60 mg) Subcutaneous every 6 months.
Length: 24-month treatment period (including a 12-month placebo-controlled period and a 12-month open-label period).
Daily supplements of calcium and vitamin D will be given to all subjects during the 24-month treatment period.
Group name:Subjects will be randomized in a 2:1 (active:placebo)
Treatment group 2: Placebo of
Treatment group 2: Placebo of denosumab 1 mg/kg body weight (up to a maximum of 60 mg) Subcutaneous every 6 months.
Length: 24-month treatment period (including a 12-month placebo-controlled period and a 12-month open-label period).
Daily supplements of calcium and vitamin D will be given to all subjects during the 24-month treatment period.
Sponsors
AMGEN INC.,
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria will include the following: • 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) o 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.
Exclusion criteria
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. - History of any solid organ or bone marrow transplant. - Evidence of untreated oral cavities or oral infections. - Recent or planned invasive dental procedure. - Surgical tooth extraction which has not healed by screening. - Currently unhealed fracture or osteotomy, as defined by orthopedic opinion. - Osteotomy within 5 months prior to screening. - Spinal fusion surgery within 5 months prior to screening or not yet healed (per orthopedic surgeon). - Rodding surgery within 5 months prior to screening or not yet healed (per orthopedic surgeon). - Serum albumin-corrected calcium 10% upper limit of normal (ULN) at screening. - Serum vitamin D 1.5 x ULN (or > 5 x ULN in subjects with dystrophinopathies) at screening. - Serum total bilirubin (TBL) > 1.5 x ULN at screening (subjects with Gilbert syndrome are eligible). - Positive blood screen for human immunodeficiency virus (HIV)-1 or -2 antibody. - Positive blood screen for hepatitis B surface antigen or hepatitis C antibody. - Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening (calculated by the bedside Schwartz equation). - Less than 2 evaluable vertebrae by DXA evaluation in the region of interest L1-L4, as confirmed by the central imaging laboratory. - Prior treatment for bone disease with any of the following at any time: − Denosumab, strontium, fluoride. − Bisphosphonates (BP), according to the following guidelines. o Zoledronic acid within 6 months prior to screening. o Oral BP or intravenous BP other than zoledronic acid, if the first dose of investigational product would be before their next scheduled BP dose would have been given. - Administration of any of the following treatment within 3 months prior to screening: o Growth hormone (unless on stable dose for at least 3 months prior to screening). o Calcitonin. o Cathepsin K inhibitor. o Other bone active drugs including anti-convulsants (except gabapentin and benzodiazepines) and heparin. o Chronic systemic ketoconazole, androgens (except subjects who have received testosterone therapy for physiologic replacement in the setting of documented hormonal deficiency), cinacalcet, aluminum, lithium, protease inhibitors, gonadotropin releasing hormone agonists. - Initiation of any of the following biologic agents within 4 weeks prior to screening: − Anti-alpha 4 integrin antibody (eg, natalizumab). − Anti-CD4/CD8 T-cells (eg, alefacept). − Anti-IL-12/IL-23 (eg, ustekinumab). − CTLA4 inhibitor (eg, abatacept). − IL1 receptor antagonist (eg, anakinra).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The primary efficacy endpoint will be the change from baseline in lumbar spine bone mineral density Z-score at 12 months and will be analyzed based on the primary dual-energy X-ray absorptiometry analysis set using an analysis of covariance (ANCOVA) model including treatment (denosumab vs placebo), baseline age, baseline bone mineral density Z-score, and underlying disease type. Measure:Change from baseline in lumbar spine bone mineral density Z-score as assessed by dual-energy X-ray absorptiometry at 12 months. Timepoints:The primary analysis will be conducted at the time of the final analysis. The final analysis for the study, including the analysis of the primary endpoint, will be performed when all enrolled subjects have had the opportunity to complete the 36-month follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Secondary efficacy endpoints will be assessed without multiplicity adjustment. Depending on the number of subjects in each subgroup, the ANCOVA model specified above will be performed by individual subgroup of interest; summary statistics for the results will include 12-month LS mean point estimate of the treatment difference (denosumab – placebo) and 2-sided 95% confidence interval of the change in bone mineral density Z-score for each subgroup, along with the subgroup-by-treatment interaction p-value. Measure: • Change from baseline in lumbar spine bone mineral density Z-score as assessed by dual-energy X-ray absorptiometry at 6, 18, 24, and 36 months. • Change from baseline in proximal femur bone mineral density Z-score as assessed by dual-energy X-ray absorptiometry at 6, 12, 18, 24, and 36 months. • 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 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). • Subject incidence of vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pretreatment. • Change from baseline in Childhood Health Questionnaire – Parent Form-50 Physical Summary Score at 12, 24, and 36 months. • Change from baseline in Childhood Health Questionnaire – Parent Form-50 Psychological Summary Score at 12, 24, and 36 months. • Change from baseline in Childhood Health Assessment Questionnaire Disability Index Score at 12, 24, and 36 months. • Change from baseline Wong-Baker Faces Pain Rating Scale 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. • | — |
Countries
Belgium, Bulgaria, Canada, Colombia, France, India, Italy, Korea South, Mexico, Peru, Russian Federation, Turkey, Ukraine, United States
Contacts
Public ContactClaudia Zamata
IQVIA RDS Peru S.R.L
Outcome results
None listed