Trial With HuMax-CD4 in Participants With Rheumatoid Arthritis (RA) Failing Treatment With Methotrexate (MTX) and a TNF-alpha Blocker

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether HuMax-CD4 is effective in the treatment of active RA in participants who have failed treatment with MTX and at least one TNF-alpha blocking agent.

Detailed Description
-----------------
This is a multi-center, double-blind, placebo-controlled, parallel-group, randomized trial of HuMax-CD4 in the treatment of participants with active RA who have failed treatment with MTX and at least one TNF-alpha blocking agent. Participants are randomized to receive one of two doses of HuMax-CD4 or placebo. The drug will be administered as a subcutaneous infusion (given just under the skin), more often in the beginning and then followed by a maintenance dose. There is a 4 week follow up period, and the final evaluation of the clinical endpoints takes place 26 weeks after treatment start. The trial lasts about 28 weeks in all.

Official Title
-----------------
A Double-Blind, Placebo-Controlled, Randomized, Parallel Group Clinical Trial of Anti-CD4 Receptor Human Monoclonal Antibody (HuMax-CD4) in Patients With Active Rheumatoid Arthritis Failing Treatment With Methotrexate and TNF-alpha Blocking Agents

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

Intervention / Treatment
-----------------
* Drug: HuMax-CD4
* Drug: Placebo
* Drug: Humax-CD4


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A diagnosis of rheumatoid arthritis according to the American College of Rheumatology 1987 revised criteria (ACR) of at least 6 months duration. Active disease at the time of screening. Failure to tolerate MTX, or lack of efficacy after a minimum of 6 months treatment with MTX. Exclusion Criteria: Active autoimmune disease requiring therapy (other than rheumatoid arthritis and secondary Sjögren's disease). Syndromes such as Fibromyalgia which require chronic pain treatment. Most past or current cancers. Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest, nasal or throat infections, tuberculosis, hepatitis B and C. History of infected joint prosthesis within 5 years. Most active medical conditions such as heart disease, kidney disease, liver disease, blood diseases, hormonal disturbances, lung disease, psychiatric disease. Drug or alcohol abuse. Pregnant or breast-feeding women may not participate. Women of childbearing potential must use either contraceptive pills or an intra-uterine device for the entire study period. Note: Other protocol defined Inclusion and Exclusion criteria may apply.

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> | Drug: Placebo<br>* Placebo was administered as a subcutaneous infusion twice (BID) with 2 weeks interval followed by administration every 4 weeks up to Week 22.<br>|
| Experimental: HuMax-CD4 80 milligrams (mg)<br> | Drug: HuMax-CD4<br>* HuMax-CD4 80 mg was administered as a subcutaneous infusion BID with 2 weeks interval followed by administration every 4 weeks up to Week 22.<br>* Other names: Zanolimumab;|
| Experimental: HuMax-CD4 160 mg<br> | Drug: Humax-CD4<br>* HuMax-CD4 160 mg was administered as a subcutaneous infusion BID with 2 weeks interval followed by administration every 4 weeks up to Week 22.<br>* Other names: Zanolimumab;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with American College of Rheumatology (ACR) 20 Response |  | At Week 14 and Week 18 | 
| Change from Baseline in Disease Activity Score (DAS) |  | Baseline up to Week 26 | 
| Change from Baseline in SFP-36 questionnaire at Week 10 and 26 |  | Baseline, Week 10 and Week 26 | 
| Change from Baseline in C-Reactive Protein (CRP) |  | Baseline up to Week 26 | 
| Change from Baseline in Erythrocyte Sedimentation Rate (ESR) |  | Baseline up to Week 26 | 
| Number of Participants with Adverse Events (AEs) |  | Day 1 up to end of study (Week 26) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Human Anti Human Antibodies (HAHA) Titres |  | Up to 26 weeks | 
| Number of Participants With Clinically Significant Laboratory Abnormalities |  | Up to 26 weeks |