A Study of the Effects of RoActemra/Actemra on Vaccination in Patients With Rheumatoid Arthritis on Background Methotrexate (VISARA)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Biological: tocilizumabBiological: 23-Valent Pneumococcal Polysaccharide VaccineBiological: Tetanus Toxoid Adsorbed Vaccine
- Registration Number
- NCT01163747
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 91
- 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- Other disease-modifying antirheumatic drugs (DMARDs) must be withdrawn before baseline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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Methotrexate tocilizumab 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. Methotrexate 23-Valent Pneumococcal Polysaccharide Vaccine 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. Methotrexate Tetanus Toxoid Adsorbed Vaccine 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. Tocilizumab + Methotrexate tocilizumab 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. Tocilizumab + Methotrexate 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. Tocilizumab + Methotrexate 23-Valent Pneumococcal Polysaccharide Vaccine 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. Tocilizumab + Methotrexate Tetanus Toxoid Adsorbed Vaccine 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. Methotrexate 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes 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
Name Time Method Percentage of Participants Who Responded to Combinations of 12 Anti-Pneumococcal Antibody Serotypes 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 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 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 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 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 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.