A Study to Assess Immune Response Following Zoster Vaccination to Subjects With Rheumatoid Arthritis Receiving Tofacitinib or Placebo With Background Methotrexate

Study Overview
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Brief Summary
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This study will evaluate immune response following administration of zoster vaccine in subjects with rheumatoid arthritis who are receiving background methotrexate and initiate 5 mg twice daily of tofacitinib or placebo for tofacitinib 2 to 3 weeks following vaccination.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 2 Study To Assess The Immune Response Following Administration Of Zoster Vaccine To Subjects With Rheumatoid Arthritis Receiving Tofacitinib (Cp-690,550) Or Placebo With Background Methotrexate Treatment

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tofacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have moderate to severe rheumatoid arthritis inadequately controlled by methotrexate as defined by the American College of Rheumatology (ACR) classification criteria for Rheumatoid arthritis, painful and swollen joint counts and C-reactive protein (CRP). Screening CRP >3 mg/L or CDAI score > 10 at screening or at baseline before vaccination. Subjects must have active disease at screening and baseline. Must be at least 50 years of age or older. Exclusion Criteria: History of receiving any varicella-zoster virus vaccine Receipt of any vaccines within 6 weeks of first dose of study treatment. Subjects with current infections or history of infections. History of recurrent (more than one episode) of herpes zoster or disseminated (a single episode) of herpes zoster or disseminated (a single episode) of herpes simplex.

Ages Eligible for Study
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Minimum Age: 50 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: Tofacitinib 5 mg BID (oral) (70 subjects)<br>Zoster vaccine will be administered to subjects on background methotrexate; treatment with 5 mg tofacitinib twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks. | Drug: Tofacitinib<br>* 5 mg twice daily of tofacitinib with background methotrexate for 12 weeks<br>|
| Placebo Comparator: Placebo tofacitinib BID (oral) (70 subjects)<br>Zoster vaccine will be administered to subjects on background methotrexate; treatment with placebo twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks. | Drug: Placebo<br>* Placebo tablets twice daily with background methotrexate for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Immunoglobulin G (IgG) Levels at Week 4 | VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA). | Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12 |  | Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination) | 
| Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12 | The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values. | Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination) | 
| Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12 | VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (>=)1.5 was defined as a responder. | Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination) |