AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment (DESIRABLE)

A Confirmatory Study of AMG 162 (Denosumab) in Patients With Rheumatoid Arthritis on DMARDs Treatment (Phase III)

To evaluate the inhibitory effect of progression, compared with placebo, in joint destruction by AMG 162 administered subcutaneously to rheumatoid arthritis participants.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: denosumab; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 679
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 162-0054

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab 6 months; denosumab administered subcutaneously every 6 months	Drug: denosumab; denosumab administered subcutaneously; Other Names: AMG 162
Experimental: Denosumab 3 months; denosumab administered subcutaneously every 3 months	Drug: denosumab; denosumab administered subcutaneously; Other Names: AMG 162
Placebo Comparator: placebo; placebo administered subcutaneously to match denosumab	Drug: placebo; placebo administered subcutaneously to match denosumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to month 6
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.	baseline to month 6
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.	baseline to month 6
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.	baseline to month 12
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.	baseline to month 12
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).	baseline to month 12

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Study Director: Tsutomu Takeuchi, Prof., Division of Rheumatology Department of Internal Medicine, Keio University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): September 19, 2017

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 25, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; RANKL; Denosumab; Developmental Phase III; AMG 162; RANK; joint damage
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: AMG162-D-J301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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 Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No