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

NCT01163747 | Completed Phase 4 Results

• 1 other identifier: NA25256
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 47

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

Secondary Outcomes (6)

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

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

• Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

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

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

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

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

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

  Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

Study Arms (2)

Methotrexate

ACTIVE COMPARATOR

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.

Biological: tocilizumab; Drug: methotrexate; Biological: 23-Valent Pneumococcal Polysaccharide Vaccine; Biological: Tetanus Toxoid Adsorbed Vaccine

Tocilizumab + Methotrexate

EXPERIMENTAL

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.

Biological: tocilizumab; Drug: methotrexate; Biological: 23-Valent Pneumococcal Polysaccharide Vaccine; Biological: Tetanus Toxoid Adsorbed Vaccine

Interventions

tocilizumab BIOLOGICAL

Intravenous repeating dose

Also known as: RoActemra, Actemra

Methotrexate; Tocilizumab + Methotrexate

methotrexate DRUG

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

Methotrexate; Tocilizumab + Methotrexate

23-Valent Pneumococcal Polysaccharide Vaccine BIOLOGICAL

Intramuscular or subcutaneous injection

Also known as: Pneumovax

Methotrexate; Tocilizumab + Methotrexate

Tetanus Toxoid Adsorbed Vaccine BIOLOGICAL

Intramuscular injection

Methotrexate; Tocilizumab + Methotrexate

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (47)

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Anniston, Alabama, 36207, United States

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Birmingham, Alabama, 35294, United States

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Huntsville, Alabama, 35801, United States

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Glendale, Arizona, 85304, United States

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Mesa, Arizona, 85202, United States

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Paradise Valley, Arizona, 85037, United States

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Paradise Valley, Arizona, 85253, United States

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Scottsdale, Arizona, 85258, United States

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Jonesboro, Arkansas, 72401, United States

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Fullerton, California, 92835, United States

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Hemet, California, 92543, United States

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San Leandro, California, 94578, United States

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Santa Maria, California, 93454, United States

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Upland, California, 91786, United States

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Bridgeport, Connecticut, 06606, United States

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Melbourne, Florida, 32901, United States

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South Miami, Florida, 33143, United States

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Tavares, Florida, 32778, United States

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Boise, Idaho, 83702, United States

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Idaho Falls, Idaho, 83404, United States

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Maywood, Illinois, 60153, United States

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Vernon Hills, Illinois, 60061, United States

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South Bend, Indiana, 46601, United States

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Baltimore, Maryland, 21224, United States

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Baltimore, Maryland, 21286, United States

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Saint Clair Shores, Michigan, 48080, United States

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Tupelo, Mississippi, 38801, United States

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Las Vegas, Nevada, 89128, United States

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Manalapan, New Jersey, 07726, United States

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Albany, New York, 12206, United States

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Belmont, North Carolina, 28012, United States

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Charlotte, North Carolina, 28210, United States

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Greenville, North Carolina, 27834, United States

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Cleveland, Ohio, 44109, United States

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Gallipolis, Ohio, 45631, United States

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Middleburg Heights, Ohio, 44130, United States

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Lake Oswego, Oregon, 97035, United States

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Duncansville, Pennsylvania, 16635, United States

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Philadelphia, Pennsylvania, 19152, United States

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Wexford, Pennsylvania, 15090, United States

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Wyomissing, Pennsylvania, 19610, United States

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Charleston, South Carolina, 29407, United States

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Orangeburg, South Carolina, 29118, United States

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Dallas, Texas, 75246, United States

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Mesquite, Texas, 75150, United States

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Tacoma, Washington, 98405, United States

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Clarksburg, West Virginia, 26301, United States

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Related Publications (1)

• Bingham CO 3rd, Rizzo W, Kivitz A, Hassanali A, Upmanyu R, Klearman M. Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA). Ann Rheum Dis. 2015 May;74(5):818-22. doi: 10.1136/annrheumdis-2013-204427. Epub 2014 Jan 21.

  PMID: 24448345 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Methotrexate; 23-valent pneumococcal capsular polysaccharide vaccine; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Micki Klearman, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: July 16, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2012
• Last Updated: December 7, 2012
• Results First Posted: December 7, 2012

Record last verified: 2012-11

Locations

US (47)