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

To evaluate the effect of denosumab on lumbar spine bone mineral density(BMD) Z-score at 12
months, as assessed by dual-energy X-ray absorptiometry (DXA), inchildren 2 to 17 years of
age with osteogenesis imperfecta.

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

- § 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.