Purpose

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.

Condition

Eligibility

Eligible Ages
Between 2 Years and 17 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Denosumab
  • Drug: Denosumab
    All subjects will receive denosumab 1 mg/kg (up to a maximum of 60 mg) given subcutaneously every 6 months for 36 months.

Recruiting Locations

Research Site
Nashville, Tennessee 37232

More Details

NCT ID
NCT02352753
Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.