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

NCT ID: NCT02352753

Last Updated: 2022-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-24
• Study Completion Date: 2022-03-26

Brief 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.

Detailed Description

To evaluate the effect of denosumab in lumbar spine bone mineral density (BMD) Z-score at 12 months, as assessed by dual-energy X-ray absorptiometry (DXA), in children 2 to 17 years of age (at the time of screening) on a 3-Month Dosing Regimen with osteogenesis imperfecta (OI)

Conditions

Osteogenesis Imperfecta

Keywords

Amgen, OI, Bone

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Denosumab

Participants received denosumab 1 mg/kg (up to a maximum of 60 mg) subcutaneously every 6 months (Q6M) for up to 36 months.

Early efficacy and PK data from Q6M dosing supported adjustment of the dosing regimen from Q6M to every 3 months (Q3M). Participants enrolled and still receiving denosumab were transitioned from Q6M to Q3M dosing schedule. Participants could transition to Q3M dosing schedule up to and including the date they attended for their month 36 visit under the Q6M dosing regimen. Those participants received denosumab during the Q3M dosing regimen for 12 months. Participants who transition to Q3M at month 18 of the Q6M dosing regimen received denosumab Q3M for up to 18 months.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Subcutaneous (SC) injection.

Interventions

Denosumab

Subcutaneous (SC) injection.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Los Angeles, California, United States

Research Site

Torrance, California, United States

Research Site

Aurora, Colorado, United States

Research Site

New Haven, Connecticut, United States

Research Site

Wilmington, Delaware, United States

Research Site

Decatur, Georgia, United States

Research Site

Indianapolis, Indiana, United States

Research Site

Iowa City, Iowa, United States

Research Site

Baltimore, Maryland, United States

Research Site

Boston, Massachusetts, United States

Research Site

Omaha, Nebraska, United States

Research Site

Nashville, Tennessee, United States

Research Site

Houston, Texas, United States

Research Site

Westmead, New South Wales, Australia

Research Site

Subiaco, Western Australia, Australia

Research Site

Brussels, , Belgium

Research Site

Ghent, , Belgium

Research Site

Leuven, , Belgium

Research Site

Sofia, , Bulgaria

Research Site

Sofia, , Bulgaria

Research Site

Varna, , Bulgaria

Research Site

Ottawa, Ontario, Canada

Research Site

Toronto, Ontario, Canada

Research Site

Montreal, Quebec, Canada

Research Site

Hradec Králové, , Czechia

Research Site

Pardubice, , Czechia

Research Site

Pilsen, , Czechia

Research Site

Prague, , Czechia

Research Site

Zlín, , Czechia

Research Site

Bordeaux, , France

Research Site

Paris, , France

Research Site

Paris, , France

Research Site

Saint-Priest-en-Jarez, , France

Research Site

Toulouse, , France

Research Site

Cologne, , Germany

Research Site

Budapest, , Hungary

Research Site

Roma, , Italy

Research Site

Verona, , Italy

Research Site

Bialystok, , Poland

Research Site

Lodz, , Poland

Research Site

Rzeszów, , Poland

Research Site

Warsaw, , Poland

Research Site

Esplugues de Llobregat, Catalonia, Spain

Research Site

Getafe, Madrid, Spain

Research Site

Valencia, Valencia, Spain

Research Site

Birmingham, , United Kingdom

Research Site

Bristol, , United Kingdom

Research Site

Glasgow, , United Kingdom

Research Site

Sheffield, , United Kingdom

Countries

United States; Australia; Belgium; Bulgaria; Canada; Czechia; France; Germany; Hungary; Italy; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2014-000184-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20130173

Identifier Type: -

Identifier Source: org_study_id