Vanderbilt Clinical Trials

• 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.

• 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.