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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01163747
First Posted: July 16, 2010
Last Update Posted: December 7, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis Biological: tocilizumab Drug: methotrexate Biological: 23-Valent Pneumococcal Polysaccharide Vaccine Biological: Tetanus Toxoid Adsorbed Vaccine Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination) ]

    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 [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination) ]

    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.


  • Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-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 [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-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 [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-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 [ Time Frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination) ]

    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, 7F, 8, 9N, 12F, 14, 18C, 19F and 23F.


  • Number of Participants With Adverse Events Through Week 8 [ Time Frame: 8 weeks ]
    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.


Enrollment: 91
Study Start Date: September 2010
Study Completion Date: June 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methotrexate
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
Intravenous repeating dose
Other Names:
  • RoActemra
  • Actemra
Drug: methotrexate
A stable dose of between 7.5 and 25 mg/week, oral or parenteral.
Biological: 23-Valent Pneumococcal Polysaccharide Vaccine
Intramuscular or subcutaneous injection
Other Name: Pneumovax
Biological: Tetanus Toxoid Adsorbed Vaccine
Intramuscular injection
Experimental: Tocilizumab + Methotrexate
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
Intravenous repeating dose
Other Names:
  • RoActemra
  • Actemra
Drug: methotrexate
A stable dose of between 7.5 and 25 mg/week, oral or parenteral.
Biological: 23-Valent Pneumococcal Polysaccharide Vaccine
Intramuscular or subcutaneous injection
Other Name: Pneumovax
Biological: Tetanus Toxoid Adsorbed Vaccine
Intramuscular injection

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01163747


  Show 47 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Micki Klearman, M.D. Genentech, Inc.
  More Information

Publications:
Bingham III C.O, Rizzo W, Klearman M, et al. Preliminary results from a controlled trial (VISARA) to evaluate the humoural immune response to vaccines in RA patients treated with tocilizumab (TCZ). Ann Rheum Dis. 2012;71(Suppl 3):345.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01163747     History of Changes
Other Study ID Numbers: NA25256
First Submitted: July 14, 2010
First Posted: July 16, 2010
Results First Submitted: November 12, 2012
Results First Posted: December 7, 2012
Last Update Posted: December 7, 2012
Last Verified: November 2012

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Vaccines
Methotrexate
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors