A Study To Assess the Immune Response Following Administration Of Influenza and Pneumococcal Vaccines To Subjects With Rheumatoid Arthritis Receiving CP-690,550 Or Placebo

Study Overview
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Brief Summary
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A Randomized, Double Blind, Placebo Controlled Phase 2 Study To assess the Immune Response Following Administration of Influenza and Pneumococcal Vaccines to Subjects with Rheumatoid Arthritis receiving CP-690,550 with and Without background Methotrexate

Official Title
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A Randomized, Double Blind, Placebo Controlled Phase 2 Study To Assess The Immune Response Following Administration Of Influenza And Pneumococcal Vaccines To Subjects With Rheumatoid Arthritis Receiving Cp-690,550 Or Placebo Cp-690,550 With And Without Background Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: CP-690,550
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must meet the American College of Rheumatology (ACR) classification criteria for the diagnosis of RA by satisfying at least four of the seven criteria. The subject must have active disease at both screening and baseline Exclusion Criteria: History of any documented influenza or pneumococcal infection within the last 3 months. Receipt of any vaccine within 1 month prior to the initial study drug administration (CP-690,550 or placebo CP-690,550). If a subject has received an influenza vaccine within 6 months or a pneumococcal vaccine within 5 years of initial study drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1: 10 mg BID CP-690,550 (100 subjects).<br>CP-690,550 will be administered for 4 weeks, vaccines will be administered at week 4. CP-690,550 will then continue for another 5 weeks at which point the immune response will be evaluated. | Drug: CP-690,550<br>* Treatment Group 1: 10 mg BID CP-690,550 (100 subjects). Strata 1: 10 mg BID CP-690,550 on background methotrexate (50 subjects); Strata 2: 10 mg BID CP-690,550 monotherapy (50 subjects).<br>|
| Placebo Comparator: Treatment Group 2:Placebo CP-690,550 (100 subjects).<br>Placebo will be administered for 4 weeks, vaccines will be administered at week 4. Placebo will then continue for another 5 weeks at which point the immune response will be evaluated. | Drug: placebo<br>* Placebo CP-690,550 (100 subjects). Strata 1: Placebo CP-690,550 on background methotrexate (50 subjects); Strata 2: Placebo CP-690,550 monotherapy (50 subjects). Influenza and pneumococcal vaccines will be administered to all subjects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Satisfactory Humoral Response to the Pneumococcal Vaccine at Visit 3 (Day 64) | Satisfactory humoral response to the pneumococcal vaccine was defined as greater than or equal to (>=) 2 fold increase in antibody concentrations from vaccination baseline (Day 29) in at least 6 of 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C). Data was stratified by the background methotrexate use. | Day 64 (End of Study [EOS]) | 
| Percentage of Participants With Satisfactory Humoral Response to the Seasonal Influenza Vaccine at Visit 3 (Day 64) | Satisfactory humoral response to the influenza vaccine was defined as >= 4 fold increase in antibody titers from vaccination baseline (Day 29) in at least 2 of 3 influenza antigens (B, H1N1, H3N2). Data was stratified by the background methotrexate use. | Day 64 (EOS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Responded to Each of the 12 Pneumococcal Antigens | Response to the pneumococcal vaccine (seroconversion) was defined as >= 2 fold increase in antibody concentrations from vaccination baseline (Day 29) in each of the 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C). Data was stratified by the background methotrexate use. | Day 64 (EOS) | 
| Percentage of Participants Who Responded to Each of the 3 Influenza Antigens | Response to the influenza vaccine (seroconversion) was defined as >= 4 fold increase in antibody titers from vaccination baseline (Day 29) in each of 3 influenza antigens (B, H1N1, H3N2). Data was stratified by the background methotrexate use. | Day 64 (EOS) | 
| Percentage of Participants With Protective Antibody Titers to the Seasonal Influenza Vaccine | Seroprotection was defined as achieving protective antibody titers to the influenza vaccine as measured by a hemagglutination inhibition (HAI) assay titer of >= 1:40 in at least 2 of 3 influenza antigens (B, H1N1, H3N2). Data was stratified by the background methotrexate use. | Day 64 (EOS) | 
| Geometric Mean Fold Rise (GMFR) of Anti-Pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens Above Vaccination Baseline Values (Day 29) | Geometric mean fold rises (GMFRs) for the 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) from pre-vaccination (Day 29) to Day 64 (Day 35 post-vaccination) were computed using the logarithmically transformed assay results. Confidence intervals (CIs) for GMFR are back transformations of a CI based on the Student t-distribution for the mean logarithm of the titers. Data was stratified by the background methotrexate use. | Day 64 (EOS) | 
| Geometric Mean Fold Rise (GMFR) of Anti-Influenza Antibody Levels to Each of the Influenza Antigens Above Vaccination Baseline Values (Day 29) | GMFRs for the 3 influenza antigens (B, H1N1, H3N2) from pre-vaccination (Day 29) to Day 64 (Day 35 post-vaccination) were computed using the logarithmically transformed assay results. CIs for GMFR are back transformations of a CI based on the Student t-distribution for the mean logarithm of the titers. Data was stratified by the background methotrexate use. | Day 64 (EOS) | 
| Geometric Mean Concentrations (GMC) of Anti-Pneumococcal Antibody | Antibody geometric mean concentration (GMC) for 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C) as measured by geometric mean of three independent determinations of the antibody response of that antigen. GMC and corresponding 2-sided 95% confidence intervals (CI) were evaluated. | Day 64 (EOS) | 
| Geometric Mean Titer (GMT) of Anti-Influenza Antibody | Antibody geometric mean titer (GMT) for 3 influenza antigens antigens (B, H1N1, H3N2) as measured by geometric mean of three independent determinations of the antibody response of that antigen. GMT and corresponding 2-sided 95% confidence intervals (CI) were evaluated. | Day 64 (EOS) |