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

Study Overview
=================
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.

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

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: denosumab
* Drug: placebo


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab 6 months<br>denosumab administered subcutaneously every 6 months | Drug: denosumab<br>* denosumab administered subcutaneously<br>* Other names: AMG 162;|
| Experimental: Denosumab 3 months<br>denosumab administered subcutaneously every 3 months | Drug: denosumab<br>* denosumab administered subcutaneously<br>* Other names: AMG 162;|
| Placebo Comparator: placebo<br>placebo administered subcutaneously to match denosumab | Drug: placebo<br>* placebo administered subcutaneously to match denosumab<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rheumatoid Arthritis, Denosumab, RANKL, RANK, AMG 162, joint damage, Developmental Phase III