AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment (DESIRABLE)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Not Applicable
Locations
Japan
Study Type
Interventional
Intervention
denosumab
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Denosumab, RANKL, RANK, AMG 162, joint damage, Developmental Phase III
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with rheumatoid arthritis according to the American College of Rheumatology (ACR) criteria for rheumatoid arthritis classification (1987 revision) or the 2010 ACR-EULAR (The European League Against Rheumatism) classification criteria for rheumatoid arthritis
Exclusion Criteria:
- Functional class IV according by the ACR revised classification (1991)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Denosumab 6 months
Denosumab 3 months
placebo
Arm Description
denosumab administered subcutaneously every 6 months
denosumab administered subcutaneously every 3 months
placebo administered subcutaneously to match denosumab
Outcomes
Primary Outcome Measures
Change in Total Sharp Score (TSS) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Total Sharp Score (TSS) from baseline to month 12 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.
Secondary Outcome Measures
Change in Total Sharp Score (TSS) From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Total Sharp Score (TSS) from baseline to month 6 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.
Change in Erosion Score From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Erosion Score from baseline to month 6 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.
Change in Joint Space Narrowing From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Joint Space Narrowing from baseline to month 6 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.
Change in Erosion Score From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Erosion Score from baseline to month 12 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.
Change in Joint Space Narrowing From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Change from baseline in Joint Space Narrowing from baseline to month 12 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
The percent change from baseline in Bone Mineral Density (BMD) to month 12 was assessed. Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA).
Full Information
NCT ID
NCT01973569
First Posted
October 25, 2013
Last Updated
February 3, 2020
Sponsor
Daiichi Sankyo, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01973569
Brief Title
AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment
Acronym
DESIRABLE
Official Title
A Confirmatory Study of AMG 162 (Denosumab) in Patients With Rheumatoid Arthritis on DMARDs Treatment (Phase III)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
October 2013 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
September 19, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the inhibitory effect of progression, compared with placebo, in joint destruction by AMG 162 administered subcutaneously to rheumatoid arthritis participants.
Detailed Description
To evaluate the inhibitory effect of progression, compared with placebo, in joint destruction by AMG 162 administered subcutaneously at a dose of 60 mg every 6 months or every 3 months for 12 months to rheumatoid arthritis participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Denosumab, RANKL, RANK, AMG 162, joint damage, Developmental Phase III
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
679 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab 6 months
Arm Type
Experimental
Arm Description
denosumab administered subcutaneously every 6 months
Arm Title
Denosumab 3 months
Arm Type
Experimental
Arm Description
denosumab administered subcutaneously every 3 months
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo administered subcutaneously to match denosumab
Intervention Type
Drug
Intervention Name(s)
denosumab
Other Intervention Name(s)
AMG 162
Intervention Description
denosumab administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo administered subcutaneously to match denosumab
Primary Outcome Measure Information:
Title
Change in Total Sharp Score (TSS) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Total Sharp Score (TSS) from baseline to month 12 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.
Time Frame
baseline to month 12
Secondary Outcome Measure Information:
Title
Change in Total Sharp Score (TSS) From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Total Sharp Score (TSS) from baseline to month 6 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.
Time Frame
baseline to month 6
Title
Change in Erosion Score From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Erosion Score from baseline to month 6 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.
Time Frame
baseline to month 6
Title
Change in Joint Space Narrowing From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Joint Space Narrowing from baseline to month 6 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.
Time Frame
baseline to month 6
Title
Change in Erosion Score From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Erosion Score from baseline to month 12 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.
Time Frame
baseline to month 12
Title
Change in Joint Space Narrowing From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Description
Change from baseline in Joint Space Narrowing from baseline to month 12 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.
Time Frame
baseline to month 12
Title
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo
Description
The percent change from baseline in Bone Mineral Density (BMD) to month 12 was assessed. Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA).
Time Frame
baseline to month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with rheumatoid arthritis according to the American College of Rheumatology (ACR) criteria for rheumatoid arthritis classification (1987 revision) or the 2010 ACR-EULAR (The European League Against Rheumatism) classification criteria for rheumatoid arthritis
Exclusion Criteria:
Functional class IV according by the ACR revised classification (1991)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tsutomu Takeuchi, Prof.
Organizational Affiliation
Division of Rheumatology Department of Internal Medicine, Keio University
Official's Role
Study Director
Facility Information:
City
Tokyo
ZIP/Postal Code
162-0054
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https:// vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Citations:
PubMed Identifier
33858976
Citation
Tanaka Y, Takeuchi T, Soen S, Yamanaka H, Yoneda T, Tanaka S, Nitta T, Okubo N, Genant HK, van der Heijde D. Effects of Denosumab in Japanese Patients With Rheumatoid Arthritis Treated With Conventional Antirheumatic Drugs: 36-month Extension of a Phase III Study. J Rheumatol. 2021 Nov;48(11):1663-1671. doi: 10.3899/jrheum.201376. Epub 2021 Apr 15.
Results Reference
derived
PubMed Identifier
31826682
Citation
Takeuchi T, Soen S, Ishiguro N, Yamanaka H, Tanaka S, Kobayashi M, Okubo N, Nitta T, Tanaka Y. Predictors of new bone erosion in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs: Analysis of data from the DRIVE and DESIRABLE studies. Mod Rheumatol. 2021 Jan;31(1):34-41. doi: 10.1080/14397595.2019.1703484. Epub 2020 Jan 9.
Results Reference
derived
Learn more about this trial
AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment
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