multicenter,single-arm study to evaluate efficacy, safety, & pharmacokinetics of denosumab in children w/ oi

Conditions: Osteogenesis Imperfecta

Summary: 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)

Eligibility criteria:
• 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.

Keywords: amgen, oi, bone