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Rheumatoid ArthritisPhase 4NCT01163747

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

A Phase 4 study testing tocilizumab, methotrexate and 23-Valent Pneumococcal Polysaccharide Vaccine in people with Rheumatoid Arthritis, run by Genentech, Inc. at 47 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
tocilizumab, methotrexate and 23-Valent Pneumococcal Polysaccharide Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
47 sitesUnited States
Study dates
Sep 2010to Jun 2012
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

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  • Other disease-modifying antirheumatic drugs (DMARDs) must be withdrawn before baseline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

Who cannot join

  • 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
Show all 9Show fewer
  • Primary or secondary immunodeficiency (history or currently active)
  • Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
  • Previous treatment with RoActemra/Actemra

Trial locations and contacts

47 sites in 1 country.

47 sites in 1 country

United States47 sites

  • Study site

    Albany, New York, 12206

  • Study site

    Anniston, Alabama, 36207

  • Study site

    Baltimore, Maryland, 21224

  • Study site

    Baltimore, Maryland, 21286

  • Study site

    Belmont, North Carolina, 28012

  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Boise, Idaho, 83702

  • Study site

    Bridgeport, Connecticut, 06606

  • Study site

    Charleston, South Carolina, 29407

  • Study site

    Charlotte, North Carolina, 28210

  • Study site

    Clarksburg, West Virginia, 26301

  • Study site

    Cleveland, Ohio, 44109

  • Study site

    Dallas, Texas, 75246

  • Study site

    Duncansville, Pennsylvania, 16635

  • Study site

    Fullerton, California, 92835

  • Study site

    Gallipolis, Ohio, 45631

  • Study site

    Glendale, Arizona, 85304

  • Study site

    Greenville, North Carolina, 27834

  • Study site

    Hemet, California, 92543

  • Study site

    Huntsville, Alabama, 35801

  • Study site

    Idaho Falls, Idaho, 83404

  • Study site

    Jonesboro, Arkansas, 72401

  • Study site

    Lake Oswego, Oregon, 97035

  • Study site

    Las Vegas, Nevada, 89128

  • Study site

    Manalapan, New Jersey, 07726

  • Study site

    Maywood, Illinois, 60153

  • Study site

    Melbourne, Florida, 32901

  • Study site

    Mesa, Arizona, 85202

  • Study site

    Mesquite, Texas, 75150

  • Study site

    Middleburg Heights, Ohio, 44130

  • Study site

    Orangeburg, South Carolina, 29118

  • Study site

    Paradise Valley, Arizona, 85037

  • Study site

    Paradise Valley, Arizona, 85253

  • Study site

    Philadelphia, Pennsylvania, 19152

  • Study site

    Saint Clair Shores, Michigan, 48080

  • Study site

    San Leandro, California, 94578

  • Study site

    Santa Maria, California, 93454

  • Study site

    Scottsdale, Arizona, 85258

  • Study site

    South Bend, Indiana, 46601

  • Study site

    South Miami, Florida, 33143

  • Study site

    Tacoma, Washington, 98405

  • Study site

    Tavares, Florida, 32778

  • Study site

    Tupelo, Mississippi, 38801

  • Study site

    Upland, California, 91786

  • Study site

    Vernon Hills, Illinois, 60061

  • Study site

    Wexford, Pennsylvania, 15090

  • Study site

    Wyomissing, Pennsylvania, 19610

Other trials in United States

About this study

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

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.

Being tested
tocilizumab, methotrexate, 23-Valent Pneumococcal Polysaccharide Vaccine, Tetanus Toxoid Adsorbed Vaccine
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tocilizumabBiological

    Also called RoActemra, Actemra

    Intravenous repeating dose

  • methotrexateDrug

    A stable dose of between 7.5 and 25 mg/week, oral or parenteral.

  • 23-Valent Pneumococcal Polysaccharide VaccineBiological

    Also called Pneumovax

    Intramuscular or subcutaneous injection

  • Tetanus Toxoid Adsorbed VaccineBiological

    Intramuscular injection

Study groups in NCT01163747
Study groupRoleWhat they receive
MethotrexateActive comparatorParticipants 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.
Receives: Biological: tocilizumab; Drug: methotrexate; Biological: 23-Valent Pneumococcal Polysaccharide Vaccine; Biological: Tetanus Toxoid Adsorbed Vaccine
Tocilizumab + MethotrexateExperimentalParticipants 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.
Receives: Biological: tocilizumab; Drug: methotrexate; Biological: 23-Valent Pneumococcal Polysaccharide Vaccine; Biological: Tetanus Toxoid Adsorbed Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

Secondary outcomes (6)

  1. 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.

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

  2. 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.

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

  3. 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).

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

  4. 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).

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

  5. 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.

    Measured: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)

  6. 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.

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2010 (estimated)
  2. Study startSep 2010
  3. Primary completionDec 2011
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01163747
Sponsor's protocol ID
NA25256
Status last verified
Nov 2012
First submitted
14 Jul 2010
Last updated
7 Dec 2012

Publications

  • Bingham CO 3rd, Rizzo W, Kivitz A, Hassanali A, Upmanyu R, Klearman M. Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA). Ann Rheum Dis. 2015 May;74(5):818-22. doi: 10.1136/annrheumdis-2013-204427. Epub 2014 Jan 21.

    PubMed 24448345

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing tocilizumab, methotrexate and 23-Valent Pneumococcal Polysaccharide Vaccine in people with Rheumatoid Arthritis, run by Genentech, Inc. at 47 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01163747, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2012.

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