Natalizumab in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate

This study has been terminated.
(The biological effect seen with natalizumab was not sufficient to warrant further development in RA.)
Information provided by:
Elan Pharmaceuticals Identifier:
First received: June 1, 2004
Last updated: June 1, 2009
Last verified: April 2009
The purpose of this study is to determine the safety, tolerability and efficacy of natalizumab in subjects diagnosed with moderate to severe rheumatoid arthritis (RA) receiving concomitant treatment with methotrexate (MTX). It is thought that natalizumab may stop the movement of certain white blood cells, known as lymphocytes, into joint tissue. These cells are thought to cause damage in the joints leading to the symptoms of RA.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: natalizumab
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Intravenous Natalizumab (300 mg) in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Receiving Concomitant Treatment With Methotrexate (MTX)

Resource links provided by NLM:

Further study details as provided by Elan Pharmaceuticals:

Primary Outcome Measures:
  • American College of Rheumatology (ACR)20. [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • American College of Rheumatology (ACR)50 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • American College of Rheumatology (ACR)70 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

Enrollment: 299
Study Start Date: May 2004
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: natalizumab Drug: natalizumab
Other Name: TYSABRI
Placebo Comparator: placebo Drug: placebo


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Subjects will be eligible to begin study participation if they meet all of the following inclusion criteria:

  • Subject is able to read, understand, and voluntarily sign the approved Informed Consent form prior to the performance of any study-specific procedures;
  • Male or female subjects, ≥18 to ≤75 years of age, who has a diagnosis of rheumatoid arthritis Functional Class 1 to 3 by the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis for at least 6 months prior to screening;
  • Subject is on a stable dose of MTX of at least 10 mg/week for ≥3 months prior to randomization (Month 0) without an adequate response;
  • Female subjects of childbearing potential agree to use adequate, contraceptive methods (either intrauterine device [IUD], oral or depot contraceptive, or barrier plus spermicide). Female subjects of childbearing potential use adequate contraception for at least 2 months prior to study entry and continue contraception for at least 3 months after their last infusion of study drug;
  • Subject is willing and able to complete all planned study procedures;
  • Subject has at least 10 painful/tender and 6 swollen joints at the Month 0 (Baseline) visit;
  • Subject has an elevated CRP level (defined as >2.87 mg/L) at Screening.

Exclusion Criteria:

Subjects will be excluded from the study if they meet any of the following exclusion criteria:

  • Subject is pregnant or lactating;
  • Subject who has experienced an inadequate therapeutic response after at least 3 months of treatment with at least one TNF-alpha inhibitor;
  • Subject who has received treatment with anakinra;
  • Subject who has received prior treatment with natalizumab;
  • Subject does not meet the following criteria regarding concomitant medications for RA:
  • Use of any oral steroid exceeding 10 mg/day of prednisone (or equivalent dose) and not administered at a stable dose for at least 1 month prior to randomization (Month 0);
  • Use of any NSAIDs unless stable for at least 1 month prior to randomization (Month 0);
  • Use of other anti-arthritic treatments, including approved or experimental oral, topical, or injectable biologics or drugs, or devices within 1 month prior to randomization (Month 0);
  • Intra-articular corticosteroid injections within 1 month prior to randomization (Month 0);
  • Treatment with any TNF-alpha inhibitor within 2 months prior to randomization (Month 0);
  • Subject who is expected to be unavailable for the duration of the trial, likely to be noncompliant with the Protocol, or felt to be unsuitable by the Investigator for any other reason;
  • Subject who has a history of a malignancy (other than basal cell carcinoma of the skin);
  • Subject who has a history of clinically significant and/or persistent gastrointestinal, pulmonary, chronic infection, cardiovascular, renal, hepatic, neurological, dermatological, immunological, major psychiatric (including drug or alcohol abusers) or hematological illness, which, in the opinion of the Investigator placed the subject at unacceptable risk for participation in the study;
  • Subject who has any laboratory test at Screening considered significantly abnormal. An alanine transaminase (ALT) or aspartate transaminase (AST) ≥1.5 x upper limits of normal (ULN) and cytopenia (included any of the following: WBC <3.5 x 1000/uL; hemoglobin [Hb] <8 g/dL; platelets <100 x 1000/uL; and/or neutrophils absolute <1.0 x 1000/uL) were considered significantly abnormal;
  • Subject who intends to donate blood or blood products during the period of the study or within 1 month following completion of the study;
  • Subject who has a positive tuberculosis (TB) skin test at Screening or within the 30 days prior to Screening (defined as ≥10 mm induration);
  • Subject who plans or requires any surgical procedure during the study treatment period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00083759

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Clinical Research Unit / University of Arizona
Tucson, Arizona, United States, 85719
United States, California
Arthritis Medical Clinic of North County, Inc.
Escondido, California, United States, 92025-4402
United States, Florida
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States, 32216
United States, Maine
Massachusetts General Hospital
Boston, Maine, United States, 02114
United States, Massachusetts
Clinical Pharmacology Study Group
Worcester, Massachusetts, United States, 01610
United States, Michigan
Justus Fiechtner, MD, PC
Lansing, Michigan, United States, 48910
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
Rheumatic Disease Associates
Willow Grove, Pennsylvania, United States, 19090
United States, Texas
Radiant Research
Dallas, Texas, United States, 75235
Canada, Newfoundland and Labrador
St. Clare's Mercy Hospital
St. John's, Newfoundland and Labrador, Canada, A1C 5B8
Canada, Ontario
The Arthritis Program Research Group Inc.
Newmarket, Ontario, Canada, L3Y 3R7
Sponsors and Collaborators
Elan Pharmaceuticals
  More Information Identifier: NCT00083759     History of Changes
Other Study ID Numbers: ELN100226-RA201 
Study First Received: June 1, 2004
Results First Received: January 27, 2009
Last Updated: June 1, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases processed this record on May 02, 2016