Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
Condition: Osteogenesis Imperfecta
MeSH terms: Osteogenesis Imperfecta
Intervention: Denosumab
Intervention description: Subcutaneous (SC) injection.
Intervention MeSH terms: Denosumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 153.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Amgen, OI, Bone

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.
    

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.