Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing

Study Overview
=================
Brief Summary
-----------------
To demonstrate the efficacy of 80 mg adalimumab monthly dosing compared with placebo and demonstrate the non-inferiority of monthly dosing of 80 mg adalimumab compared with dosing of 40 mg adalimumab every other week.

Detailed Description
-----------------
The objective of this study is to demonstrate the efficacy of 80 mg adalimumab monthly dosing compared with placebo as measured by ACR20 response criteria following 12 weeks of therapy. The study is also designed to demonstrate the non-inferiority of monthly dosing of 80 mg adalimumab compared with dosing of 40 mg adalimumab eow as measured by ACR20 response criteria at Week 12.

Official Title
-----------------
A Multi-center, Randomized, Double-blind,Placebo-controlled Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing

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

Intervention / Treatment
-----------------
* Drug: adalimumab
* Drug: Placebo
* Drug: adalimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject > 18 years of age Subject has a diagnosis of RA as defined by the 1987-revised ACR-classification criteria and has a disease duration for a minimum of three months Subject must meet the following two criteria: a) At least 6 swollen joints out of 66 assessed, or b) At least 6 tender joints out of 68 assessed If a subject is on MTX, the doses must be stable for at least 4 weeks prior to Screening blood draw and follow standard recommendations for MTX treatment Subject is judged to be in generally good health as determined by the principal investigator Exclusion Criteria: Subject has previous exposure to any systemic anti-TNF therapy (eg, infliximab, etanercept, certolizumab pegol or golimumab) including adalimumab Subject has a history of acute inflammatory joint disease of different origin other than RA Subject has been treated with any investigational biologic agents Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study Female subject who is pregnant or breast-feeding or considering becoming pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 12 weeks, 40mg adalimumab remaining 12 weeks | Drug: Placebo<br>* Pre-filled syringe. See arm for more detail<br>|
| Active Comparator: 40 mg<br>40 mg every other week | Drug: adalimumab<br>* Pre-filled syringe. See arm for more detail<br>* Other names: Humira;|
| Active Comparator: 80 mg<br>80 mg monthly | Drug: adalimumab<br>* Pre-filled syringe. See arm for more detail<br>* Other names: Humira;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Responders According to the American College of Rheumatology (ACR) 20 Response Criteria at Week 12 Involving the Comparison of Adalimumab 80 mg Monthly Dose Versus Placebo and Adalimumab 40 mg Every Other Week (Eow) | Comparison of adalimumab 80 mg monthly dose versus placebo and adalimumab 40 mg eow in the number of responders with ACR criteria improvement consisting of 20%, (ACR20) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20% improvement in 3 of the following 5 criteria: [1] physician's global assessment of disease activity (PGA), [2] subject's assessment of disease activity, [3] subject's assessment of pain, [4] subject's assessment of physical disability via a health assessment questionnaire disability index(HAQ-DI), and [5] C-reactive protein (CRP) at each visit | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed) | The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function. | Baseline and Week 12 | 
| Within Group Mean Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF]) | The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function. | Baseline and Week 12 | 
| Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed) | The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function. | Baseline and Week 12 | 
| Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF]) | The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function. | Baseline and Week 12 |