TIV and High Dose TIV in Subjects With Rheumatoid Arthritis

NCT01436370 | Completed Phase 2 Results

• 1 other identifier: 10-0076
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Influenza

Keywords

influenza, rheumatoid arthritis, TNF-alpha-inhibitor, Fluzone®, Fluzone® High Dose

Outcome Measures

Primary Outcomes (2)

• Number of RA Participants in the 2011-2012 Season Who Achieved Seroconversion at Day 21 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received

  Blood was collected from RA participants prior to vaccination and at the 21 day follow up visit for testing in the HAI assay with 2011-2012 seasonal influenza vaccine strains virus as the assay antigens. A participant met the threshold of seroconversion if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more.

  Day 0 prior to and Day 21 following immunization

• Number of RA Participants in the 2012-2013 Season Who Achieved Seroconversion at Day 21 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received

  Blood was collected from RA participants prior to vaccination and at the 21 day follow up visit for testing in the HAI assay with 2012-2013 seasonal influenza vaccine strains virus as the assay antigens. A participant met the threshold of seroconversion if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more.

  Day 0 prior to and Day 21 following immunization

Secondary Outcomes (12)

• Number of Participants Reporting Vaccine-related Serious Adverse Events (SAEs) Throughout the Course of the Study.

  Day 0 to Day 180

• Geometric Mean Titers (GMT) for Each of the Specific Influenza Strains Included in Vaccine Received by Participants in the 2011-2012 Season

  Days 0, 7, 21 and 180

• Geometric Mean Titers (GMT) for Each of the Specific Influenza Strains Included in Vaccine Received by Participants in the 2012-2013 Season

  Days 0, 7, 21 and 180

• Number of Participants Reporting Solicited Systemic Symptoms Based on a Functional Grading Scale

  Day 0 to Day 7

• Number of Participants Reporting Fever

  Day 0 to Day 7

Study Arms (4)

Group 1 Controls

EXPERIMENTAL

40 (up to 50) adults, healthy gender and age-matched controls, given a single 15 mcg intramuscular dose of Sanofi Pasteur Fluzone®

Biological: Trivalent inactivated influenza vaccine

Group 2

EXPERIMENTAL

40 (up to 50) adults with Rheumatoid Arthritis receiving TNF-alpha-inhibitor therapy, given a single 60 mcg intramuscular dose of Sanofi Pasteur Fluzone® High Dose.

Biological: Trivalent inactivated influenza vaccine

Group 2 Controls

EXPERIMENTAL

40 (up to 50) adults, healthy gender and age-matched controls, given a single 60 mcg intramuscular dose of Sanofi Pasteur Fluzone® High Dose.

Biological: Trivalent inactivated influenza vaccine

Group 1

EXPERIMENTAL

40 (up to 50) adults with Rheumatoid Arthritis receiving TNF-alpha-inhibitor therapy, given a single 15 mcg intramuscular dose of Sanofi Pasteur Fluzone®

Biological: Trivalent inactivated influenza vaccine

Interventions

Trivalent inactivated influenza vaccine BIOLOGICAL

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.

Group 2; Group 2 Controls

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

MeSH Terms

Conditions

Influenza, Human; Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Jack Stapleton, MD
• Organization: Department of Internal Medicine, University of Iowa

jack-stapleton@uiowa.edu

319-356-3168

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 19, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2013
• Last Updated: December 24, 2014
• Results First Posted: May 16, 2014

Record last verified: 2013-02

Locations

US (1)