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
ClinicalTrials.gov Identifier:
NCT01163747
First received: July 14, 2010
Last updated: November 12, 2012
Last verified: November 2012
  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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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:

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) ] [ 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.



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) ] [ 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.


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

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01163747

  Hide Study Locations
Locations
United States, Alabama
Anniston, Alabama, United States, 36207
Birmingham, Alabama, United States, 35294
Huntsville, Alabama, United States, 35801
United States, Arizona
Glendale, Arizona, United States, 85304
Mesa, Arizona, United States, 85202
Paradise Valley, Arizona, United States, 85253
Paradise Valley, Arizona, United States, 85037
Scottsdale, Arizona, United States, 85258
United States, Arkansas
Jonesboro, Arkansas, United States, 72401
United States, California
Fullerton, California, United States, 92835
Hemet, California, United States, 92543
San Leandro, California, United States, 94578
Santa Maria, California, United States, 93454
Upland, California, United States, 91786
United States, Connecticut
Bridgeport, Connecticut, United States, 06606
United States, Florida
Melbourne, Florida, United States, 32901
South Miami, Florida, United States, 33143
Tavares, Florida, United States, 32778
United States, Idaho
Boise, Idaho, United States, 83702
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Maywood, Illinois, United States, 60153
Vernon Hills, Illinois, United States, 60061
United States, Indiana
South Bend, Indiana, United States, 46601
United States, Maryland
Baltimore, Maryland, United States, 21224
Baltimore, Maryland, United States, 21286
United States, Michigan
Saint Clair Shores, Michigan, United States, 48080
United States, Mississippi
Tupelo, Mississippi, United States, 38801
United States, Nevada
Las Vegas, Nevada, United States, 89128
United States, New Jersey
Manalapan, New Jersey, United States, 07726
United States, New York
Albany, New York, United States, 12206
United States, North Carolina
Belmont, North Carolina, United States, 28012
Charlotte, North Carolina, United States, 28210
Greenville, North Carolina, United States, 27834
United States, Ohio
Cleveland, Ohio, United States, 44109
Gallipolis, Ohio, United States, 45631
Middleburg Heights, Ohio, United States, 44130
United States, Oregon
Lake Oswego, Oregon, United States, 97035
United States, Pennsylvania
Duncansville, Pennsylvania, United States, 16635
Philadelphia, Pennsylvania, United States, 19152
Wexford, Pennsylvania, United States, 15090
Wyomissing, Pennsylvania, United States, 19610
United States, South Carolina
Charleston, South Carolina, United States, 29407
Orangeburg, South Carolina, United States, 29118
United States, Texas
Dallas, Texas, United States, 75246
Mesquite, Texas, United States, 75150
United States, Washington
Tacoma, Washington, United States, 98405
United States, West Virginia
Clarksburg, West Virginia, United States, 26301
Sponsors and Collaborators
Genentech
Investigators
Study Director: Micki Klearman, M.D. Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01163747     History of Changes
Other Study ID Numbers: NA25256
Study First Received: July 14, 2010
Results First Received: November 12, 2012
Last Updated: November 12, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 26, 2014