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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01163747
• Other study ID #: NA25256
• Status: Completed
• Phase: Phase 4
• First received: July 14, 2010
• Last updated: November 12, 2012
• Start date: September 2010
• Est. completion date: June 2012

Study information

• Verified date: November 2012
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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• Other disease-modifying antirheumatic drugs (DMARDs) must be withdrawn before baseline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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• tocilizumab
Intravenous repeating dose

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
• Tetanus Toxoid Adsorbed Vaccine
Intramuscular injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Percentage of Participants Who Responded to Combinations 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)	No
Secondary	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.	Baseline (Week 3) and Week 8 (5 weeks post-vaccination)	No
Secondary	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).	Baseline (Week 3) and Week 8 (5 weeks post-vaccination)	No
Secondary	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).	Baseline (Week 3) and Week 8 (5 weeks post-vaccination)	No
Secondary	Percentage of Participants Who Responded to Each of the 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, 7F, 8, 9N, 12F, 14, 18C, 19F and 23F.	Baseline (Week 3) and Week 8 (5 weeks post-vaccination)	No
Secondary	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.	8 weeks	No