TIV and High Dose TIV in Subjects With Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2013
• Main ID: NCT01436370
• Date of registration: 15/09/2011
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: TIV and High Dose TIV in Subjects With Rheumatoid Arthritis
• Scientific title: A Phase II Study in Adults With Rheumatoid Arthritis Receiving TNF-alpha-inhibitor Therapy to Assess the Immunogenicity and Safety of Trivalent Inactivated Vaccine (TIV) and High Dose Trivalent Inactivated Vaccine (High-Dose TIV) Administered at Two Dosage Levels
• Date of first enrolment: October 2011
• Target sample size: 200
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01436370
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Countries of recruitment

United States

Contacts

• Name: Jack Stapleton

Key inclusion & exclusion 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


Age minimum: 18 Years
Age maximum: 64 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Influenza

Intervention(s)

Biological: Sanofi Pasteur Fluzone®

Biological: Sanofi Pasteur Fluzone® High Dose

Primary Outcome(s)

The proportion of subjects who receive high dose influenza vaccine with seroconversion against each of the 3 specific influenza strains in vaccine the subject received compared to those receiving standard influenza vaccine. [Time Frame: Day 21 following immunization]

Secondary Outcome(s)

Immune response in Rheumatoid Arthritis (RA) subjects who are receiving TNFi therapy as measured by Geometric Mean titer (GMT) for each of the specific influenza strains included in vaccine the subject received will be compared to CS. [Time Frame: Days 7, 21 and 180]

Occurrence of solicited local adverse events (AEs) within 8 days post vaccination (Day 0-7). [Time Frame: Day 0 to Day 7]

Occurrence of solicited systemic AEs within 8 days post vaccination (Day 0-7). [Time Frame: Day 0 to Day 7]

Occurrence of vaccine-related serious adverse events (SAEs) throughout the course of the study. [Time Frame: Day 0 to Day 180]

Occurrence of worsening rheumatoid arthritis status during the course of the study, based on the RAPID3 score from the NP2 questionnaire [Time Frame: Day 0 to Day 180]

The proportion of RA subjects on TNFi therapy with seroconversion against each of the specific influenza strains included in vaccine the subject received compared to control subjects (CS). [Time Frame: Days 7, 21 and 180]

The proportion of subjects who receive high dose influenza vaccine with seroconversion against each of the 3 specific influenza strains in vaccine the subject received, compared to those receiving standard influenza vaccine. [Time Frame: Days 7 and 180 following immunization]

Secondary ID(s)

10-0076

N01AI80008C

Source(s) of Monetary Support

Please refer to primary and secondary sponsors