InfluenzaPhase 2NCT01436370
TIV and High Dose TIV in Subjects With Rheumatoid Arthritis
A Phase 2 study testing Trivalent inactivated influenza vaccine in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Trivalent inactivated influenza vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jun 2013
- Phase
- Phase 2
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa - Vaccine Research & Education Unit
Iowa City, Iowa, 52242-2600
About this study
Official 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
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.
Read the detailed description
This is a randomized, double-blinded, Phase II study in adults with Rheumatoid Arthritis receiving TNF-alpha inhibitor therapy, aged 18 years to 64 years of age. This study is designed to investigate the immunogenicity, safety, and reactogenicity of two different doses of inactivated trivalent influenza virus vaccine given at two dose levels (15 mcg and 60 mcg) administered IM in individuals with rheumatoid arthritis receiving anti-TNF-alpha therapy or age and gender matched control subjects. The study is conducted over two seasons, 2011-2012 and 2012-2013. Subjects enrolling between October 2011 and February 2012 will receive the 2011-2012 vaccine, while those enrolling after July 2012 will receive the 2012-2013 vaccine. Immunogenicity testing will determine the proportion of subjects in each group with titer a 4-fold rise in HAI titers (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/=1:10 and a minimum four-fold rise in post-vaccination HAI titer) against each of the specific influenza strains included in vaccine the subject received at day 21 following vaccination. The proportion of subjects in each group achieving a serum HAI titer of >/= 1:40 or a 4-fold rise in HAI titer or greater in HAI titer against each strain in the vaccine compared to the controls subjects. Safety testing will assess the occurrence of vaccine-associated Serious adverse events (SAEs) throughout the course of the study, and the occurrence of solicited local and systemic adverse events (AEs) within 8 days post vaccination. Solicited AEs (including rheumatoid arthritis clinical status) will be assessed during the course of the study. Subjects will have four face to face visits and one telephone contact. Day 0 will include the consent process, a medical history and physical exam for the RA subjects to assess the activity of their RA at the time of enrollment, vital signs, phlebotomy for prevaccine serology. Subjects will be randomized to receive IM seasonal TIV or High-Dose TIV at this visit and will receive the assigned vaccine. They will be observed for 20 minutes and will be taught to fill out a 7 day memory aid that will assess daily temperature, local and systemic reactogenicity. A telephone call will be made to assess reactogenicity and to review the memory aid on day 3. Subjects will return on day 7 for review of the memory aid, AEs/SAEs, vital signs and phlebotomy for serology. A physical exam will be performed if indicated. They will return on day 21 and at 6 months for review of AEs/SAEs, vital signs and phlebotomy for serology. A physical exam will be performed if indicated.
- Conditions
- Influenza
- Being tested
- Trivalent inactivated influenza vaccine
- Keywords
- influenza, rheumatoid arthritis, TNF-alpha-inhibitor, Fluzone®, Fluzone® High Dose
- Medical subject headings
- Influenza, Human, Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trivalent inactivated influenza vaccineBiological
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.
Trivalent inactivated influenza vaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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® Receives: 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. Receives: 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. Receives: 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® Receives: Biological: Trivalent inactivated influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof; resulted in a congenital anomaly/birth defect; or may have jeopardized the participant or required intervention to prevent one of these outcomes. Association to vaccination was determined by a study clinician licensed to make medical diagnosis.
Measured: 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
Blood was collected for HAI assay at Day 0 prior to vaccination and again at 7, 21 and 180 days following vaccination. The HAI assay was conducted with the three antigens in the 2011-2012 seasonal inactivated TIV. Within each 2011-2012 study arm, geometric mean titers and 95% confidence intervals were calculated for each antigen separately.
Measured: 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
Blood was collected for HAI assay at Day 0 prior to vaccination and again at 7, 21 and 180 days following vaccination. The HAI assay was conducted with the three antigens in the 2012-2013 seasonal inactivated TIV. Within each 2012-2013 study arm, geometric mean titers and 95% confidence intervals were calculated for each antigen separately.
Measured: Days 0, 7, 21 and 180
Number of Participants Reporting Solicited Systemic Symptoms Based on a Functional Grading Scale
Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, chills, arthralgia, shivering, and asthenia for 8 days after vaccination (Day 0-7) based on their interference with daily activities, with a severity grade of mild meaning no interference, moderate as some interference and severe as significant interference/prevented daily activity. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Measured: Day 0 to Day 7
Number of Participants Reporting Fever
Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 38.0 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 38.0 degrees Celsius or higher on any of the 8 days.
Measured: Day 0 to Day 7
Number of Participants Reporting Solicited Local Injection Site Reactions Based on a Functional Grading Scale
Participants maintained a memory aid to record daily the occurrence of local injection site reactions of pain, tenderness, redness, and swelling for 8 days after vaccination (Day 0-7) based on their interference with daily activities, with a severity grade of mild meaning no interference, moderate as some interference and severe as significant interference/prevented daily activity. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Measured: Day 0 to Day 7
Number of Participants Reporting Solicited Quantitative Local Injection Site Reactions
Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
Measured: Day 0 to Day 7
Number of RA Participants in the 2011-2012 Season Who Achieved Seroconversion at Days 7 and 180 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 Days 7 and 180 follow up visits 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.
Measured: Day 0 prior to and Days 7 and 180 following immunization
Number of RA Participants in the 2012-2013 Season Who Achieved Seroconversion at Days 7 and 180 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 Days 7 and 180 follow up visits 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.
Measured: Day 0 prior to and Days 7 and 180 following immunization
Number of RA Participants With a Worsening Rheumatoid Arthritis Status During the Course of the Study, Based on the RAPID3 Score From the NP2 Questionnaire
The RAPID 3 score is an index of the three patient-reported measures from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) R808 and serves as an assessment of patient status for those with rheumatoid arthritis. The score consists of the cumulative total of the Function (FN), Pain (PN), and Patient Global (PTGL) values. The severity of the RAPID 3 score is categorized as: >12=High Severity; 6.1-12=Moderate Severity; 3.1-6=Low Severity; and ≤3=Remission. The NP2 questionnaire was completed by RA participants at all clinic visits. Scores at Days 7, 21 and 180 were compared to Day 0 to determine worsening, defined as moving from the baseline category to a more severe category.
Measured: Day 0 to Days 7, 21 and 180
Number of Participants in the 2011-2012 Season Who Achieved Seroconversion at Days 7, 21 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Blood was collected from all participants prior to vaccination and at the Days 7, 21 and 180 follow up visits 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.
Measured: Day 0 prior to and Days 7, 21 and 180 following immunization
Number of Participants in the 2012-2013 Season Who Achieved Seroconversion at Days 7, 21 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Blood was collected from all participants prior to vaccination and at the Days 7, 21 and 180 follow up visits 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.
Measured: Day 0 prior to and Days 7, 21 and 180 following immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionFeb 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01436370
- Sponsor's protocol ID
- 10-0076
- Status last verified
- Feb 2013
- First submitted
- 15 Sep 2011
- Last updated
- 24 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01436370
- Acronym / sponsor ID
- 10-0076
- Conditions
- Influenza
- Keywords
- influenza, rheumatoid arthritis, TNF-alpha-inhibitor, Fluzone®, Fluzone® High Dose
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Oct 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 19 Sep 2011 (estimated)
- Results
- Posted 16 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomized, double-blinded, Phase II study in adults with Rheumatoid Arthritis receiving TNF-alpha inhibitor therapy, aged 18 years to 64 years of age. This study is designed to investigate the immunogenicity, safety, and reactogenicity of two different doses of inactivated trivalent influenza virus vaccine given at two dose levels (15 mcg and 60 mcg) administered IM in individuals with rheumatoid arthritis receiving anti-TNF-alpha therapy or age and gender matched control subjects. The study is conducted over two seasons, 2011-2012 and 2012-2013. Subjects enrolling between October 2011 and February 2012 will receive the 2011-2012 vaccine, while those enrolling after July 2012 will receive the 2012-2013 vaccine. Immunogenicity testing will determine the proportion of subjects in each group with titer a 4-fold rise in HAI titers (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/=1:10 and a minimum four-fold rise in post-vaccination HAI titer) against each of the specific influenza strains included in vaccine the subject received at day 21 following vaccination. The proportion of subjects in each group achieving a serum HAI titer of >/= 1:40 or a 4-fold rise in HAI titer or greater in HAI titer against each strain in the vaccine compared to the controls subjects. Safety testing will assess the occurrence of vaccine-associated Serious adverse events (SAEs) throughout the course of the study, and the occurrence of solicited local and systemic adverse events (AEs) within 8 days post vaccination. Solicited AEs (including rheumatoid arthritis clinical status) will be assessed during the course of the study. Subjects will have four face to face visits and one telephone contact. Day 0 will include the consent process, a medical history and physical exam for the RA subjects to assess the activity of their RA at the time of enrollment, vital signs, phlebotomy for prevaccine serology. Subjects will be randomized to receive IM seasonal TIV or High-Dose TIV at this visit and will receive the assigned vaccine. They will be observed for 20 minutes and will be taught to fill out a 7 day memory aid that will assess daily temperature, local and systemic reactogenicity. A telephone call will be made to assess reactogenicity and to review the memory aid on day 3. Subjects will return on day 7 for review of the memory aid, AEs/SAEs, vital signs and phlebotomy for serology. A physical exam will be performed if indicated. They will return on day 21 and at 6 months for review of AEs/SAEs, vital signs and phlebotomy for serology. A physical exam will be performed if indicated.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 Controls | Experimental | Biological: Trivalent inactivated influenza vaccine40 (up to 50) adults, healthy gender and age-matched controls, given a single 15 mcg intramuscular dose of Sanofi Pasteur Fluzone® |
| Group 2 | Experimental | Biological: Trivalent inactivated influenza vaccine40 (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. |
| Group 2 Controls | Experimental | Biological: Trivalent inactivated influenza vaccine40 (up to 50) adults, healthy gender and age-matched controls, given a single 60 mcg intramuscular dose of Sanofi Pasteur Fluzone® High Dose. |
| Group 1 | Experimental | Biological: Trivalent inactivated influenza vaccine40 (up to 50) adults with Rheumatoid Arthritis receiving TNF-alpha-inhibitor therapy, given a single 15 mcg intramuscular dose of Sanofi Pasteur Fluzone® |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trivalent inactivated influenza vaccineInactivated 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. | Biological | Group 2, Group 2 Controls |
| Trivalent inactivated influenza vaccineInactivated 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. | Biological | Group 1, Group 1 Controls |
Primary outcome
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
Time frame: Day 0 prior to and Day 21 following immunization
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.
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
Time frame: Day 0 prior to and Day 21 following immunization
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.
12 secondary outcomes
Number of Participants Reporting Vaccine-related Serious Adverse Events (SAEs) Throughout the Course of the Study.
Time frame: 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
Time frame: 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
Time frame: Days 0, 7, 21 and 180
Number of Participants Reporting Solicited Systemic Symptoms Based on a Functional Grading Scale
Time frame: Day 0 to Day 7
Number of Participants Reporting Fever
Time frame: Day 0 to Day 7
Number of Participants Reporting Solicited Local Injection Site Reactions Based on a Functional Grading Scale
Time frame: Day 0 to Day 7
Number of Participants Reporting Solicited Quantitative Local Injection Site Reactions
Time frame: Day 0 to Day 7
Number of RA Participants in the 2011-2012 Season Who Achieved Seroconversion at Days 7 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Time frame: Day 0 prior to and Days 7 and 180 following immunization
Number of RA Participants in the 2012-2013 Season Who Achieved Seroconversion at Days 7 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Time frame: Day 0 prior to and Days 7 and 180 following immunization
Number of RA Participants With a Worsening Rheumatoid Arthritis Status During the Course of the Study, Based on the RAPID3 Score From the NP2 Questionnaire
Time frame: Day 0 to Days 7, 21 and 180
Number of Participants in the 2011-2012 Season Who Achieved Seroconversion at Days 7, 21 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Time frame: Day 0 prior to and Days 7, 21 and 180 following immunization
Number of Participants in the 2012-2013 Season Who Achieved Seroconversion at Days 7, 21 and 180 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received
Time frame: Day 0 prior to and Days 7, 21 and 180 following immunization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Influenza
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
Not yet recruitingPhase 1
Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates
Influenza
RecruitingPhase 1
pH1N1 Blinded Challenge Study
Influenza
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of MK-1406/CD388 for Prevention of Influenza (MK-1406-005/CD388.SQ.3.06)
Influenza
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trivalent inactivated influenza vaccine in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 12 inclusion and 24 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 24 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 May 2014). 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?
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 (time frame: Day 0 prior to and Day 21 following immunization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Dec 2014.