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

NCT02352753 | Terminated Phase 3 Results DMC

• 2 other identifiers: 201301732014-000184-40
• Study Type: interventional
• Target: 153
• Locations: 13 countries
• Sites: 49

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.

Conditions

Osteogenesis Imperfecta

Keywords

Amgen, OI, Bone

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months

  Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.

  Baseline and 12 months

Secondary Outcomes (15)

• Change From Baseline in Lumbar Spine BMD Z-score at 6 Months

  Baseline and 6 months

• Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months

  Baseline, 6 and 12 months

• Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture

  Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months

• Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture

  Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months

• Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture

  Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months

Study Arms (1)

Denosumab

EXPERIMENTAL

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.

Drug: Denosumab

Interventions

Denosumab DRUG

Subcutaneous (SC) injection.

Denosumab

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead

Study Sites (49)

Research Site

Los Angeles, California, 90027, United States

Location

Research Site

Torrance, California, 90502, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

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New Haven, Connecticut, 06510, United States

Location

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Wilmington, Delaware, 19803, United States

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Decatur, Georgia, 30033, United States

Location

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Indianapolis, Indiana, 46202, United States

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Iowa City, Iowa, 52242, United States

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Baltimore, Maryland, 21205, United States

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Boston, Massachusetts, 02115, United States

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Omaha, Nebraska, 68114, United States

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Nashville, Tennessee, 37232, United States

Location

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Houston, Texas, 77030, United States

Location

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Westmead, New South Wales, 2145, Australia

Location

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Subiaco, Western Australia, 6008, Australia

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Sofia, 1606, Bulgaria

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Sofia, 1784, Bulgaria

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Varna, 9010, Bulgaria

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Ottawa, Ontario, K1H 8L1, Canada

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Toronto, Ontario, M5G 1X8, Canada

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Montreal, Quebec, H4A 0A9, Canada

Location

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Hradec Králové, 500 05, Czechia

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Pardubice, 532 03, Czechia

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Pilsen, 305 99, Czechia

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Prague, 140 59, Czechia

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Zlín, 762 75, Czechia

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Bordeaux, 33076, France

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Paris, 75012, France

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Paris, 75743, France

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Saint-Priest-en-Jarez, 42270, France

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Toulouse, 31059, France

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Cologne, 50931, Germany

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Budapest, 1094, Hungary

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Roma, 00161, Italy

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Verona, 37126, Italy

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Bialystok, 15-274, Poland

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Lodz, 91-738, Poland

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Rzeszów, 35-301, Poland

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Warsaw, 04-730, Poland

Location

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Esplugues de Llobregat, Catalonia, 08950, Spain

Location

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Getafe, Madrid, 28905, Spain

Location

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Valencia, Valencia, 46026, Spain

Location

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Birmingham, B4 6NH, United Kingdom

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Bristol, BS2 8AE, United Kingdom

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Glasgow, G51 4TF, United Kingdom

Location

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Sheffield, S10 2TH, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2015
• First Posted: February 2, 2015
• Study Start: June 24, 2015
• Primary Completion: March 26, 2022
• Study Completion: March 26, 2022
• Last Updated: December 28, 2022
• Results First Posted: December 28, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

BU (3); AU (2); US (13); FR (5); IT (2); BE (3); DE (1); CA (3); CZ (5); PL (4); ES (3); GB (4); HU (1)