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:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01163747
First received: July 14, 2010
Last updated: November 12, 2012
Last verified: November 2012

July 14, 2010
November 12, 2012
September 2010
December 2011   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]

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.

Humoral immune response 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine (Pneumovax), defined as proportion of patients who respond to ≥ 6 of 12 anti-pneumococcal antibody serotypes [ Time Frame: From Week 3 to Week 8 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01163747 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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.
  • Proportion of patients responding 5 weeks after vaccination with Pneumovax to combinations of the 12 serotypes measured [ Time Frame: from Week 3 to Week 8 ] [ Designated as safety issue: No ]
  • Humoral immune response 5 weeks after vaccination with tetanus toxoid (TT) vaccine [ Time Frame: from Week 3 to Week 8 ] [ Designated as safety issue: No ]
  • Levels of anti-pneumococcal antibody 5 weeks after vaccination [ Time Frame: from Week 3 to Week 8 ] [ Designated as safety issue: No ]
  • Levels of anti-tetanus antibody 5 weeks after vaccination [ Time Frame: from Week 3 to Week 8 ] [ Designated as safety issue: No ]
  • Proportion of patients who respond for each of the 12 individual anti-pneumococcal antibody serotypes 5 weeks after vaccination with Pneumovax [ Time Frame: from Week 3 to Week 8 ] [ Designated as safety issue: No ]
  • Safety and tolerability: Adverse events, laboratory parameters [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of the Effects of RoActemra/Actemra on Vaccination in Patients With Rheumatoid Arthritis on Background Methotrexate (VISARA)
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

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Rheumatoid Arthritis
  • 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
  • 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.
    Interventions:
    • Biological: tocilizumab
    • Drug: methotrexate
    • Biological: 23-Valent Pneumococcal Polysaccharide Vaccine
    • Biological: Tetanus Toxoid Adsorbed Vaccine
  • 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.
    Interventions:
    • Biological: tocilizumab
    • Drug: methotrexate
    • Biological: 23-Valent Pneumococcal Polysaccharide Vaccine
    • Biological: Tetanus Toxoid Adsorbed Vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
June 2012
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 64 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01163747
NA25256
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Micki Klearman, M.D. Genentech, Inc.
Genentech, Inc.
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP