Overview

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

Status:
Active, not recruiting
Trial end date:
2022-05-09
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Amgen
Treatments:
Denosumab
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.