TIV and High Dose TIV in Subjects With Rheumatoid Arthritis
Condition: Influenza
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Trivalent inactivated influenza vaccine; Trivalent inactivated influenza vaccine
Intervention description: Inactivated trivalent influenza virus vaccine (Sanofi Pasteur Fluzone® High Dose [60 mcg x 3 strains]), as a single intramuscular dose. 80 and up to 100 subjects. Subjects enrolling between October 2011 and February 2012 will receive the 2011-2012 vaccine and subjects enrolling after July 2012 will receive the 2012-2013 vaccine.; Inactivated trivalent influenza virus vaccine (Sanofi Pasteur Fluzone® [15 mcg x 3 strains]), as a single intramuscular dose. 80 and up to 100 subjects. Subjects enrolling between October 2011 and February 2012 will receive the 2011-2012 vaccine and subjects enrolling after July 2012 will receive the 2012-2013 vaccine.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: influenza, rheumatoid arthritis, TNF-alpha-inhibitor, Fluzone®, Fluzone® High Dose

Summary:

      A randomized, double-blinded, Phase II study in adults with Rheumatoid Arthritis receiving
      TNF-alpha-inhibitor therapy aged 18 to 64 years of age and healthy gender-and age-matched
      control subjects . This study will investigate the immunogenicity, safety, and reactogenicity
      of two different doses of inactivated trivalent influenza virus vaccine (Sanofi Pasteur
      Fluzone [15 mcg x 3 strains] and Sanofi Pasteur Fluzone High Dose [60 mcg x 3 strains])
      administered intramuscularly in individuals with rheumatoid arthritis receiving
      anti-TNF-alpha (TNFi) therapy and healthy age- and gender- matched controls.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria for RA Subjects

          -  Male or non-pregnant female between the ages of 18 and 64 years, inclusive, who has
             stable RA and has received TNFi therapy during the previous 3 months.

          -  Female subjects: for the 30 days prior to enrollment through 30 days following receipt
             of TIV or HTIV vaccine must fulfill one of the following: (i) she is not able to bear
             children because she has been surgically sterilized (tubal ligation or hysterectomy)
             for at least one year or is at least 1 year post-menopausal or (ii) she agrees to
             practice effective methods of contraception including, but not limited to, abstinence,
             barrier methods (such as a condom or diaphragm) used with a spermicide, birth control
             pills, patches or hormonal shots or hormonal implants, NuvaRing and IUDs (intrauterine
             devices). Adherence to contraceptive method will be captured on the appropriate case
             report form (CRF).

          -  In good health, as determined by vital signs (see toxicity table in section 9.2.1.1),
             medical history to ensure any existing medical diagnoses or conditions are stable and
             not considered clinically significant, and physical examination.

          -  Intend to be available through 6 months following receipt of vaccine.

          -  Able to understand and comply with planned study procedures.

          -  Provide written informed consent prior to initiation of any study procedures.

        Inclusion Criteria for Healthy Subjects

          -  Male or non-pregnant female between the ages of 18 and 64 years, inclusive.

          -  Female subjects: for the 30 days prior to enrollment through 30 days following receipt
             of TIV or HTIV vaccine must fulfill one of the following: (i) she is not able to bear
             children because she has been surgically sterilized (tubal ligation or hysterectomy)
             for at least one year or is at least 1 year post-menopausal or (ii) she agrees to
             practice effective methods of contraception including, but not limited to, abstinence,
             barrier methods (such as a condom or diaphragm) used with a spermicide, birth control
             pills, patches or hormonal shots or hormonal implants, NuvaRing and IUDs (intrauterine
             devices). Adherence to contraceptive method will be captured on the appropriate case
             report form (CRF).

          -  In good health, as determined by vital signs (see toxicity table in section 9.2.1.1),
             medical history to ensure any existing medical diagnoses or conditions are stable and
             not considered clinically significant, and physical examination.

          -  Intend to be available through 6 months following receipt of vaccine.

          -  Able to understand and comply with planned study procedures.

          -  Provide written informed consent prior to initiation of any study procedures.

        Exclusion Criteria:

        Exclusion Criteria for all Subjects

          -  For subjects enrolled after July 2012: Enrolled in this study during the 2011-2012 flu
             season.

          -  Has received the seasonal influenza vaccine for the current season. For subjects
             enrolling between October 2011 and February 2012, this is the 2011-2012 seasonal
             influenza vaccine. For subjects enrolling after July 2012, this is the 2012-2013
             seasonal influenza vaccine.

          -  Has a known allergy to eggs, egg proteins or other components in the vaccines (i.e.
             formaldehyde, gelatin sodium phosphate, sodium chloride, octylphenol ethoxylate).

          -  Has a known or suspected latex allergy or sensitivity.

          -  Has a positive urine or serum pregnancy test within 24 hours prior to vaccination (if
             female of childbearing potential as defined in Inclusion criterion 2), or women who
             are breastfeeding.

          -  Has a history of severe reactions following immunization with contemporary influenza
             virus vaccines.

          -  Has an active neoplastic disease or a history of any hematologic malignancy (cancers
             of blood or bone marrow) or current bleeding or blood clotting disorder.

          -  For "healthy volunteer" (without RA) subjects: Long term (at least 14 days of
             prednisone 2 mg/kg or equivalent other glucocorticoid) use of oral, parenteral or
             high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent)
             within the preceding 6 months. (Nasal and topical steroids are allowed.)

          -  Has a diagnosis of a current and uncontrolled major psychiatric disorder.

          -  Has been hospitalized in the past 10 years for psychiatric illness, suicide attempt,
             or confinement for danger to self or others.

          -  Is receiving listed psychiatric drugs as below*. Subjects who are receiving a single
             antidepressant drug and are stable for at least 3 months prior to enrollment, without
             decompensating are allowed enrollment into the study.

             * aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine,
             thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine,
             quetiapine, trifluoperazine, chlorprothixene, chlorpromazine, perphenazine,
             trifluopromazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate,
             lithium citrate, lamotrigine, prochlorperazine, paliperidone or iloperidone.

          -  Has a history of receiving immunoglobulin or other blood product within the 3 months
             prior to vaccination in this study.

          -  Has received an experimental/investigational agent (vaccine, drug, biologic, device,
             blood product, or medication) within 28 days prior to vaccination in this study, or
             expects to receive an experimental/investigational agent within the study time period
             (180 days after vaccination in this study).

          -  Is participating or plans to participate in another clinical trial with a licensed
             product during the 6-month study period.

          -  Has received any other licensed vaccines within 14 days (for inactivated vaccines) or
             21 days (for live vaccines) prior to vaccination in this study, or expects to receive
             a licensed vaccine during the 21 days after vaccination in this study.

          -  Has received antiviral agent against influenza A and/or B within 48 hours prior to
             vaccination in this study. Antiviral agents should not be administered until 2 weeks
             after vaccination in this study unless medically necessary.

          -  Has an acute or chronic medical condition other than RA that, in the opinion of the
             investigator, would interfere with the evaluation of responses (this includes, but is
             not limited to: known chronic liver, lung or heart disease, chronic anemia, (non-RA
             subjects only), metabolic disorders such as diabetes (resolved gestational diabetes is
             acceptable), significant renal disease, transplant recipients, system lupus
             erythematosus, psoriatic arthritis or gout).

          -  Has a moderate to severe acute illness and/or an oral temperature greater than or
             equal to 100.4 degrees Fahrenheit, within 72 hours prior to vaccination. (This may
             result in a temporary delay of vaccination).

          -  Immunosuppression as a result of an underlying illness or treatment other than RA
             therapy, or use of anti-cancer chemotherapy or radiation therapy within the preceding
             36 months.

          -  Known infection with HIV, Hepatitis B or Hepatitis C infection or autoimmune
             hepatitis.

          -  Has a history of alcohol or drug abuse in the last 5 years.

          -  Has a history of Guillain-Barré Syndrome.

          -  Has any condition that would, in the opinion of the site investigator, place the
             subject at an unacceptable risk or render the subject unable to meet the requirements
             of the protocol.