To evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis

• Register: CTRI
• Last refreshed on: 29 May 2023
• Main ID: CTRI/2018/05/013954
• Date of registration: 17-05-2018
• Prospective Registration: Yes
• Primary sponsor: Amgen Technology Pvt Ltd
• Public title: To evaluate the Safety and Efficacy 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
• Date of first enrolment: 11-10-2018
• Target sample size: 150
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=21765
• Study type: Interventional
• Study design: Other Method of generating randomization sequence:Other Method of allocation concealment:Not Applicable Blinding and masking:Double Blind Double Dummy
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Colombia, France, India, Italy, Mexico, Peru, Republic of Korea, Romania, Russian Federation, Turkey, Ukraine, United States of America

Contacts

• Name: Himani Parikh
• Affiliation: Amgen Technology Private Limited

• Name: Himani Parikh
• Affiliation: Amgen Technology Private Limited

Key inclusion & exclusion criteria

Inclusion criteria: 1. Male or female subjects, age 5 to 17 years, inclusive, at the time of informed consent.



2. 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



3. 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)



4. Subjects who are on systemic GC only as replacement therapy for adrenal

insufficiency are not eligible for the study



5. 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



6. 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 greater than or equal to 2 long-bone

fractures by age 10 years or greater than or equal to 3 long-bone fractures at any age up to 17 years) and

lumbar spine BMD Z-score less than or equal to -2.0, as assessed by the central imaging vendor
Exclusion criteria: 1. Current hyperthyroidism (unless well controlled on stable antithyroid therapy)



2. Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy)



3. History of hyperparathyroidism



4. Current hypoparathyroidism



5. Current adrenal insufficiency as the sole indication for GC therapy



6. Duchenne muscular dystrophy with symptomatic cardiac abnormality



7. Current malabsorption



8. Known intolerance to calcium or vitamin D supplements



9. 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 infections or other active infection that, in the opinion of the investigator, might compromise the safety of the subject



10. History of malignancy



11. History of any solid organ or bone marrow transplant



12. Evidence of untreated oral cavities or oral infections



13. Recent or planned invasive dental procedure



14. Surgical tooth extraction which has not healed by screening



15. Currently unhealed fracture or osteotomy, as defined by orthopedic opinion



16. Osteotomy within 5 months prior to screening



17. Spinal fusion surgery within 5 months prior to screening or not yet healed (per orthopaedic surgeon)



18. Rodding surgery within 5 months prior to screening or not yet healed (per orthopedic surgeon)



19. Anticipated major skeletal surgery (eg, rodding surgery, spinal surgery) within the next 12 months from day 1



20. Planned orthopedic surgery that, in the opinion of the investigator, would require missing any dose of investigational product in year one or 2 or more doses thereafter



21. History of rare hereditary problems of fructose intolerance



22. History of long QT syndrome



23. History of alcohol or drug abuse



24. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion



25. Serum albumin-corrected calcium < lower limit of normal (LLN) or > 10% upper limit of normal (ULN) at screening



26. Serum vitamin D <20 ng/mL at screening (rescreening for vitamin D level <20 ng/mL will be allowed, after adequate supplementation)



27. Serum phosphorus < LLN at screening



28. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 x ULN (or >5 x ULN in subjects with dystrophinopathies) at screening



29. Serum total bilirubin (TBL) > 1.5 x ULN at screening (subjects with Gilbert syndrome are eligible)



30. Positive blood screen for human immunodeficiency virus (HIV)-1 or -2 antibody



31. Positive blood screen for hepatitis B surface antigen or hepatitis C antibody



32. Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening (calculated by the bedside Schwartz equa

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Glucocorticoid-induced Osteoporosis Health Condition 2: M818- Other osteoporosis without currentpathological fracture

Intervention(s)

Intervention1: Denosumab presented as a 70 mg/mL solution containing 1.7 mL in a 3 mL vial: Investigational treatment arm: Denosumab 1 mg/kg body weight (BW) (up to a maximum of 60 mg) SC injection Q6M for the first 12 months.
Further all subjects will receive open-label denosumab Q6M for the next 12 months (last injection to be
administered at month 18).
Control Intervention1: Placebo will be presented as
a solution otherwise identical in appearance and composition to denosumab, except without the
active ingredient.: Placebo: subcutaneous (SC) injection every 6 months (Q6M) for the first 12 months

Primary Outcome(s)

Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 12 monthsTimepoint: Baseline & 12 months

Secondary Outcome(s)

Change from baseline in growth velocity, determined by calculating age-adjusted

Z-scores for height, weight, and BMI, at 12, 24, and 36 monthsTimepoint: Baseline, 12, 24, and 36 months

Change from baseline in proximal femur BMD Z-score as assessed by DXA at 6, 12, 18,

24, and 36 monthsTimepoint: Baseline, 6, 12, 18,24, and 36 months

Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, and 18 monthsTimepoint: at 1, 10, and 30 days, and 3, 6, 12, and 18 months

Change from baseline in CHQ-PF-50 Psychological Summary Score at 12, 24, and

36 monthsTimepoint: Baseline, 12, 24, and

36 months

Subject incidence of vertebral and nonvertebral fractures at 12, 24, and 36 months

compared to pretreatmentTimepoint: at 12, 24, and 36 months

compared to pretreatment

Change from baseline in CHQ-PF-50 Physical Summary Score at 12, 24, and 36 monthsTimepoint: Baseline, 12, 24, and 36 months

Change from baseline in CHAQ Disability Index Score at 12, 24, and 36 monthsTimepoint: Baseline, 12, 24, and

36 months

Change from baseline Wong-Baker Faces Pain Rating Scale

(WBFPRS) at 12, 24, and 36 monthsTimepoint: Baseline, 12, 24, and 36 months

Change from baseline in lumbar spine BMD Z-score as assessed by DXA at 6, 18, 24,

and 36 monthsTimepoint: Baseline, 6, 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-treatmentTimepoint: 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)Timepoint: at 12, 24, and 36 months compared to

pretreatment

Secondary ID(s)

NCT03164928

Source(s) of Monetary Support

Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799

Ethics review

Status: Approved
Approval date: 27/07/2018
Contact:

Institutional Ethics Committee, Gandhi Medical College, Secunderabad â?? 500003

Status: Approved
Approval date: 26/09/2018
Contact:

Institutional Ethics Committee, KLE University, Belgaum

Status: Approved
Approval date: 23/03/2019
Contact:

Institutional Review Board, CMC, Vellore

Status: Approved
Approval date: 03/06/2019
Contact:

Sir Ganga Ram Hospital Ethics Committee