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A Study of the Effects of RoActemra/Actemra on Vaccination in Patients With Rheumatoid Arthritis on Background Methotrexate (VISARA)

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

tocilizumab

methotrexate

23-Valent Pneumococcal Polysaccharide Vaccine

Tetanus Toxoid Adsorbed Vaccine

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients, ≥ 18 to < 65 years of age
Rheumatoid Arthritis (RA) of > 6 months duration at baseline (American College of Rheumatology criteria)
Willing to receive immunization with pneumococcal polysaccharide and tetanus toxoid adsorbed vaccines
Previous immunization with pneumococcal polysaccharide must have occurred ≥ 3 years of baseline, with tetanus containing vaccine ≥ 5 years
Methotrexate therapy for at least 8 weeks prior to baseline at stable dose of 7.5-25 mg/week (oral or parenteral)
Other disease-modifying antirheumatic drugs (DMARDs) must be withdrawn before baseline
Oral corticosteroids must be at stable dose of < 10 mg/day prednisone or equivalent
Body weight ≤ 150 kg at screening

Exclusion Criteria:

Major surgery (including joint surgery) within 12 weeks prior to baseline or planned major surgery within 8 weeks after baseline
History of or current inflammatory joint disease or rheumatic autoimmune disease other than RA
Pre-existing central nervous system demyelinating or seizure disorders
Active current or history of recurrent bacterial, viral fungal, mycobacterial and other infections
Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to baseline or oral antibiotics within 2 weeks prior to baseline
Active tuberculosis requiring treatment within 3 years prior to baseline
Primary or secondary immunodeficiency (history or currently active)
Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
Previous treatment with RoActemra/Actemra

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Methotrexate

Tocilizumab + Methotrexate

Arm Description

Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.

Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes

Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of > 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.

Secondary Outcome Measures

Percentage of Participants Who Responded to Combinations of 12 Anti-Pneumococcal Antibody Serotypes

Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination

A positive response to the tetanus toxoid vaccination was defined as antibody levels ≥ 0.2 IU/mL for participants with Baseline tetanus antibody levels < 0.1 IU/mL, or a 4-fold increase in antibody levels compared with Baseline for participants with Baseline tetanus antibody levels ≥ 0.1 IU/mL.

Change From Baseline in Levels of Anti-pneumococcal Antibody 5 Weeks After Vaccination

Levels of anti-pneumococcal antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).

Change From Baseline in Levels of Anti-tetanus Antibody 5 Weeks After Vaccination

Levels of anti-tetanus antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).

Percentage of Participants Who Responded to Each of the 12 Anti-Pneumococcal Antibody Serotypes

Number of Participants With Adverse Events Through Week 8

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any AE that is fatal or is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Full Information

NCT ID

NCT01163747

First Posted

July 14, 2010

Last Updated

November 12, 2012

Sponsor

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01163747

Brief Title

A Study of the Effects of RoActemra/Actemra on Vaccination in Patients With Rheumatoid Arthritis on Background Methotrexate (VISARA)

Official Title

A Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Effects of Tocilizumab on Vaccination in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate

Study Type

Interventional

2. Study Status

Record Verification Date

November 2012

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary

This randomized, parallel-group, open-label study will evaluate the effect of Actemra (tocilizumab) on vaccination in patients with active rheumatoid arthritis who have an inadequate response to methotrexate and who have had an inadequate clinical response or were intolerant to treatment with one or more anti-tumor necrosis factor (anti-TNF) therapies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methotrexate

Arm Type

Active Comparator

Arm Description

Arm Title

Tocilizumab + Methotrexate

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

tocilizumab

Other Intervention Name(s)

RoActemra, Actemra

Intervention Description

Intravenous repeating dose

Intervention Type

Drug

Intervention Name(s)

methotrexate

Intervention Description

A stable dose of between 7.5 and 25 mg/week, oral or parenteral.

Intervention Type

Biological

Intervention Name(s)

23-Valent Pneumococcal Polysaccharide Vaccine

Other Intervention Name(s)

Pneumovax

Intervention Description

Intramuscular or subcutaneous injection

Intervention Type

Biological

Intervention Name(s)

Tetanus Toxoid Adsorbed Vaccine

Intervention Description

Intramuscular injection

Primary Outcome Measure Information:

Title

Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes

Description

Time Frame