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

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ClinicalTrials.gov Identifier: NCT03164928
Recruitment Status : Recruiting
First Posted : May 24, 2017
Last Update Posted : July 25, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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).

Condition or disease Intervention/treatment Phase
Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis Drug: Denosumab Other: Placebo Phase 3

Detailed Description:

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 Phase: 3 Indication: Glucocorticoid-induced Osteoporosis

Primary Objective: 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 years of age with Glucocorticoid (GC)-induced osteoporosis (GiOP).

Secondary Objective(s): To evaluate the effect of denosumab in children 5 to 17 years of age with GiOP with respect to:

  • Change in lumbar spine BMD Z-score as assessed by DXA from baseline to 6, 18, 24, and 36 months
  • Change in proximal femur BMD Z-score as assessed by DXA from baseline to 6, 12, 18, 24, and 36 months
  • Incidence of X-ray confirmed long-bone fractures and new and worsening vertebral fractures from pretreatment to posttreatment at 12, 24, and 36 months
  • Incidence of improving vertebral fractures from pretreatment to posttreatment at 12, 24, and 36 months (overall, among subjects with clinical fracture reduction, and among subjects with clinical fracture increase)
  • Incidence of pretreatment compared with posttreatment vertebral and nonvertebral fractures at 12, 24, and 36 months
  • Change in Childhood Health Questionnaire - Parent Form-50 (CHQ-PF-50) Physical Summary Score at 12, 24, and 36 months
  • Change in CHQ-PF-50 Psychological Summary Score at 12, 24, and 36 months
  • Change in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12, 24, and 36 months
  • Change in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12, 24, and 36 months
  • Change in growth velocity, determined by calculating age-adjusted Z-scores for height, weight, and body mass index (BMI), at 24 and 36 months
  • Serum concentration of denosumab at 1 and 10 days, and 6, 12, and 18 months (additional serum denosumab pharmacokinetics [PK] samples to be collected at day 30 and month 3 in a PK/bone turnover marker [BTM] substudy of up to 100 subjects) Hypotheses: The hypothesis of this study is that the change from baseline in lumbar spine BMD Z-score following 12 months of denosumab treatment in children 5 to 17 years of age with GiOP will be greater than placebo.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
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
Actual Study Start Date : May 7, 2018
Estimated Primary Completion Date : March 31, 2026
Estimated Study Completion Date : March 27, 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Denosumab

Arm Intervention/treatment
Placebo
SC Q6M placebo
Other: Placebo
SC Q6M placebo

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




Primary Outcome Measures :
  1. Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 12 months [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 6, 18, 24, and 36 months. [ Time Frame: 6 - 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.

  2. Change from baseline in proximal femur BMD Z-score as assessed by DXA at 6, 12, 18, 24, and 36 months. [ Time Frame: 6 - 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.

  3. 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 [ Time Frame: 12, 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

  4. Subject incidence of improving vertebral fractures at 12, 24, and 36 months compared to pretreatment [ Time Frame: 12, 24, and 36 months ]
    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)

  5. Subject incidence of vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pretreatment. [ Time Frame: 6 - 36 months ]
    Number of subjects with vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pretreatment.

  6. Change from baseline in CHQ-PF-50 Physical Summary Score at 12, 24, and 36 months. [ Time Frame: 6 - 36 months ]
    Change from baseline in CHQ-PF-50 (Childhood Health Questionnaire - Parent Form-50) Physical Summary Score at 12, 24, and 36 months

  7. Change from baseline in CHQ-PF-50 Psychological Summary Score at 12, 24, and 36 months [ Time Frame: 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

  8. Change from baseline in CHAQ Disability Index Score at 12, 24, and 36 months [ Time Frame: 12, 24, and 36 months ]
    Change from baseline in CHAQ (Childhood Health Assessment Questionnaire) Disability Index Score at 12, 24, and 36 months

  9. Change from baseline WBFPRS at 12, 24, and 36 months [ Time Frame: 12, 24, and 36 months ]
    Change from baseline WBFPRS (Wong-Baker Faces Pain Rating Scale) at 12, 24, and 36 months

  10. 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 [ Time Frame: 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

  11. Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, and 18 months [ Time Frame: Days 1, 10, and 30, and months 3, 6, 12, and 18. ]
    Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, and 18 months



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
    • 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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03164928


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03164928     History of Changes
Other Study ID Numbers: 20140444
2016-003083-39 ( EudraCT Number )
First Posted: May 24, 2017    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:
Denosumab
Pediatric GIOP
Glucocorticoid-induced
Osteoporosis

Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Denosumab
Glucocorticoids
Bone Density Conservation Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists