Natalizumab in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate

Rheumatoid Arthritis Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00083759
• Other study ID #: ELN100226-RA201
• Status: Terminated
• Phase: Phase 2
• First received: June 1, 2004
• Last updated: July 14, 2016
• Start date: May 2004

Study information

• Verified date: April 2009
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 299
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• natalizumab

• placebo

Locations

Country	Name	City	State
Canada	The Arthritis Program Research Group Inc.	Newmarket	Ontario
Canada	St. Clare's Mercy Hospital	St. John's	Newfoundland and Labrador
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Maine
United States	Radiant Research	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Arthritis Medical Clinic of North County, Inc.	Escondido	California
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Justus Fiechtner, MD, PC	Lansing	Michigan
United States	Clinical Research Unit / University of Arizona	Tucson	Arizona
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Biogen	Elan Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No