Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI

Phase 3TerminatedNCT02352753

Amgen153 enrolled

Overview

This is a prospective, multicenter, single-arm study in children 2 to 17 years of age with OI to evaluate efficacy and safety of denosumab.

To evaluate the effect of denosumab in lumbar spine bone mineral density (BMD) Z-score at 12 months, as assessed by dual-energy X-ray absorptiometry (DXA), in children 2 to 17 years of age (at the time of screening) on a 3-Month Dosing Regimen with osteogenesis imperfecta (OI)

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

153

Conditions

Osteogenesis Imperfecta

Interventions

DenosumabDRUG

Subcutaneous (SC) injection.

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

• Eligibility criteria relates to initial enrollment into this study (6-Month Dosing Regimen). Subjects reconsenting to a 3-Month Dosing Regimen will not repeat eligibility assessments Inclusion Criteria: • Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI Clinical severity of OI as defined by 2 or more prevalent vertebral compression fractures; OR1 prevalent vertebral compression fracture and 1 or more nonvertebral fractures within the previous 2 years; OR 3 or more fractures within the previous 2 years. Exclusion Criteria: * Inability or unwillingness to comply with the requirements for frequent calcium and phosphorus monitoring for 14 days after the first dose of denosumab (only applies to the first 5 subjects age 11 to17 enrolled in the study and the first 5 subjects of any age meeting the criteria for increased bone turnover * Currently unhealed fracture or osteotomy as defined by orthopedic opinion * Osteotomy within 5 months of screening * Evidence of untreated oral cavities or oral infections * Recent or planned invasive dental procedure * Surgical tooth extraction which has not healed by screening * History of an electrophoresis pattern inconsistent with type I to IV OI * History of genetic testing results inconsistent with type I to IV OI * Abnormalities of the following per central laboratory reference ranges at screening: Serum albumin corrected calcium \< lower limit of normal (LLN) Serum vitamin D \< 20 ng/mL; re-screening for Vitamin D level \< 20 ng/mL will be allowed, after adequate supplementation * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 1.5 x upper limit of normal (ULN) * Total bilirubin (TBL) \> 1.5 x ULN (subjects with Gilbert syndrome are eligible) * Serum phosphorus \< LLN * Serum alkaline phosphatase \> 20% above the ULN or \> 20% below the LLN * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 (calculated bythe Schwartz equation at screening) Evidence of any of 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 * Current, uncontrolled hypercalcemia (albumin-corrected serum Ca \>10% ULN) * History of osteomalacia or rickets (chart review) * Other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia) * History of autoimmune disease * History of rare hereditary problems of fructose intolerance * Positive blood screen for human immunodeficiency virus -1 or -2 antibody * Positive blood screen for hepatitis B surface antigen or hepatitis C antibody * Received other osteoporosis treatment or bone active treatment with the following guidelines: * Prior treatment with * denosumab * fluoride or strontium for bone disease (fluoride taken for routine dental care is permitted) * parathyroid hormone (PTH) or PTH derivatives within 12 months prior to screening * zoledronic acid within 6 months prior to screening * oral bisphosphonates or intravenous bisphosphonates other than zoledronic acid if the first dose of denosumab would be before their next scheduled bisphosphonate dose would have been given * Administration of systemic glucocorticoids (≥ 5.0 mg prednisone equivalents/day for more than 10 days) within 3 months of screening. * Topical and inhaled glucocorticoids will be allowed * Administration of any of the following treatment within 3 months of screening: * Growth hormone (subjects on stable dose of growth hormone for at least 3 months prior to screening will be allowed) * Currently receiving treatment in another investigational drug study, or less than 30 days since ending treatment on another investigational drugstudy(s), or current or planned participation in a clinical trial that would preclude compliance with study requirements Other inclusion/exclusion criteria may apply.

Locations (49)

Outcomes

Primary Outcomes

Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months

Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.

Time frame: Baseline and 12 months

Secondary Outcomes

Change From Baseline in Lumbar Spine BMD Z-score at 6 Months

Lumbar spine BMD was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.

Time frame: Baseline and 6 months

Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months

Proximal femur (total hip and femoral neck) BMD Z-score was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.

Time frame: Baseline, 6 and 12 months

Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture

Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months

Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture

Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.