Natalizumab in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate

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)

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: placebo; Drug: natalizumab

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1C 5B8
      • St. Clare's Mercy Hospital
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 3R7
      • The Arthritis Program Research Group Inc.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Clinical Research Unit / University of Arizona
  • California
    • Escondido, California, United States, 92025-4402
      • Arthritis Medical Clinic of North County, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
  • Maine
    • Boston, Maine, United States, 02114
      • Massachusetts General Hospital
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Justus Fiechtner, MD, PC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Willow Grove, Pennsylvania, United States, 19090
      • Rheumatic Disease Associates
  • Texas
    • Dallas, Texas, United States, 75235
      • Radiant Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: placebo
ACTIVE_COMPARATOR: natalizumab	Drug: natalizumab; Other Names: TYSABRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American College of Rheumatology (ACR)20.	≥20% reduction from baseline in painful/tender joint count and swollen joint count and ≥20% improvement in at least three of five secondary clinical parameters (e.g., subject global assessment, physician global assessment, pain scale, disability score, and an acute phase reactant)	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American College of Rheumatology (ACR)50	≥50% reduction from baseline in painful/tender joint count and swollen joint count and ≥50% improvement in at least three of five secondary clinical parameters (e.g., subject global assessment, physician global assessment, pain scale, disability score, and an acute phase reactant)	Month 6
American College of Rheumatology (ACR)70	≥70% reduction from baseline in painful/tender joint count and swollen joint count and ≥70% improvement in at least three of five secondary clinical parameters (e.g., subject global assessment, physician global assessment, pain scale, disability score, and an acute phase reactant)	Month 6

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: Elan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (ACTUAL): February 1, 2005

Study Registration Dates

• First Submitted: June 1, 2004
• First Submitted That Met QC Criteria: June 2, 2004
• First Posted (ESTIMATE): June 3, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): July 18, 2016
• Last Update Submitted That Met QC Criteria: July 14, 2016
• Last Verified: April 1, 2009

More Information

Terms related to this study

• 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; Immunologic Factors; Natalizumab
• Other Study ID Numbers: ELN100226-RA201