Rheumatoid Arthritis
Conditions
Brief 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.
Interventions
DRUGnatalizumab
DRUGplacebo
Sponsors
Elan Pharmaceuticals
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology (ACR)20. | Month 6 | ≥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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology (ACR)50 | Month 6 | ≥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) |
| American College of Rheumatology (ACR)70 | Month 6 | ≥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) |
Countries
Canada, United States
Participant flow
Recruitment details
First patient entered 24 May 2004, study terminated 28 February 2005. A total of 299 patients were evaluable for safety and 273 patients for efficacy. Study conducted in Argentina, Australia, Canada, Czech Republic, Poland, Slovakia, and the United States.
Pre-assignment details
Patients who met these criteria were randomized to natalizumab or placebo: aged 18-75 with a diagnosis of rheumatoid arthritis (RA) Functional Class 1-3 for ≥ 6 months, on a stable dose of methotrexate (MTX), having ≥ 10 painful/tender joints, and with elevated C-reactive protein. Stratification based on baseline number of painful/tender joints.
Participants by arm
| Arm | Count |
|---|---|
| Natalizumab Natalizumab 300 mg as monthly IV infusions + methotrexate (MTX) | 137 |
| Placebo Placebo IV infusions + methotrexate (MTX) | 136 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Inadequate Therapeutic Response | 32 | 35 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-Compliance | 1 | 0 |
| Overall Study | Other | 14 | 13 |
| Overall Study | Sponsor's Discretion | 28 | 29 |
| Overall Study | Subject Withdrew Consent | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Natalizumab |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 10.4 | 52.3 years STANDARD_DEVIATION 10.5 | 50.9 years STANDARD_DEVIATION 10.5 |
| Baseline Count of Painful/Tender Joints <20 | 43 participants | 87 participants | 44 participants |
| Baseline Count of Painful/Tender Joints >20 | 93 participants | 186 participants | 93 participants |
| Sex: Female, Male Female | 107 Participants | 218 Participants | 111 Participants |
| Sex: Female, Male Male | 29 Participants | 55 Participants | 26 Participants |
Outcome results
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)
Time frame: Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | American College of Rheumatology (ACR)20. | 59 participants |
| Placebo | American College of Rheumatology (ACR)20. | 45 participants |
p-value: 0.089Cochran-Mantel-Haenszel
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)
Time frame: Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | American College of Rheumatology (ACR)50 | 23 participants |
| Placebo | American College of Rheumatology (ACR)50 | 15 participants |
p-value: 0.171Cochran-Mantel-Haenszel
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)
Time frame: Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | American College of Rheumatology (ACR)70 | 13 participants |
| Placebo | American College of Rheumatology (ACR)70 | 10 participants |
p-value: 0.526Cochran-Mantel-Haenszel