InfluenzaPhase 4FLU2NCT03686514
The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics
A Phase 4 study testing FLUARIX QUADRIVALENT in people with Influenza, run by Emory University at 1 site in United States.
Trial summary
The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system. Read more about this study
- Who is it for?
- Ages 42 to 71 years
- Conditions the study is for
- Influenza
- What is being tested?
- FLUARIX QUADRIVALENT
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2018to 20 Jun 2020
- 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 42 to 71 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of informed consent and provision of written informed consent before any study procedures.
- Capable of attending all study visits according to the study schedule.
- Males or females born between 1968-1977 or 1948-1957.
- Are in good health, as determined by medical history and targeted physical exam related to this history.
- Oral temperature is less than 38 degrees Celsius.
- Resting pulse rate is between 50 and 100 beats per minute.
- Female subjects of childbearing age must have a negative urine pregnancy test within 24 hours before study vaccination.
- Have received the influenza vaccine at least 3 of the past 5 years or have received the influenza vaccine in 2 or less of the past 5 years.
Who cannot join
- Have an acute illness within 72 hours before vaccination.
- Have any condition that, in the opinion of the principal investigator, would place the subject at an unacceptable risk of harm or confound the interpretation of the study results.
- Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination.
- Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
- Have known HIV, hepatitis B, or hepatitis C infection.
- Have a known history of autoimmune disease.
Show all 14Show fewer
- Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination.
- Have taken high-dose inhaled corticosteroids within 30 days before study vaccination.
- Have received, or plan to receive, any licensed live vaccine within 30 days, or any licensed inactivated vaccine within 14 days, prior to, or after, study vaccination.
- Have planned receipt of any unlicensed or investigational medications, biologics, or vaccines for the duration of subject study participation.
- Have received immunoglobulin or other blood products, with the exception of Rho D immunoglobulin, within 90 days prior to study vaccination.
- Have donated blood or blood products within 30 days before study vaccination, or within 60 days after study vaccination, or plan to donate blood within 30 days of the last blood draw.
- Have known hypersensitivity or allergy to eggs, egg protein, chicken protein, or other compounds of the study vaccine.
- Have a history of severe reactions following vaccination with influenza virus vaccines.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Hope Clinic of the Emory Vaccine Center
Atlanta, Georgia, 30317
About this study
The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system.
Read the detailed description
Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated 3-5 million cases of severe illness, and 250,000 to 500,000 deaths worldwide each year. In the United States, the Centers for Disease Control and Prevention (CDC) reports that influenza has resulted in 9.2-35.6 million illnesses with 12,000-56,000 deaths annually since 2010. There is an urgent need to better understand the immunologic responses to current licensed vaccines in order to develop a more effective vaccine that does not rely on annual updates, provides broad protection, and is durable; i.e., a universal influenza vaccine.
The immune response to the influenza vaccine is affected by many parameters, including prior imprinting to a specific influenza strain based on birth cohort, as well as prior influenza vaccination. The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses (IAVs) and two influenza B viruses (IBVs). The approved seasonal influenza vaccine will be given for each season of influenza: 2018-2019, 2019-2020, and 2020-2021.
This study is a prospective pilot study conducted over the course of three years (with three specific influenza seasons studied). For each year (2018-2019, 2019-2020, and 2020-2021), two cohorts of 10 participants each, who are in good health and meet all eligibility criteria, will be recruited. The influenza A virus subtype H3N2 cohort (N=30 total, 10 per year) will consist of participants born between 1968-1977, and the influenza A virus subtype H1N1 cohort (N=30 total, 10 per year) will consist of participants born between 1948-1957. Each participant will make a total of six visits to the Hope Clinic. Day 1 will include the informed consent process, and screening to ensure the subject meets all inclusion criteria and meets no exclusion criteria. For the consenting and eligible subject, the visit will also include pre-vaccination phlebotomy for baseline immunogenicity laboratory assays. After baseline sample collection, the participants will receive the FDA-approved seasonal influenza vaccine. Subsequent study visits up to 180 days post-vaccination will include collection for immunogenicity assays.
This study is not powered to test a formal null hypothesis. Rather, it is a hypothesis-generating investigation that will hopefully lead to larger trials based on the findings. The study will be conducted over the course of three years to increase the total sample population size and to validate the findings over different influenza seasons.
- Conditions
- Influenza
- Being tested
- FLUARIX QUADRIVALENT
- Keywords
- Flu vaccine, Influenza vaccine, Immune response, Influenza strain
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLUARIX QUADRIVALENTBiological
The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses.
| Study group | Role | What they receive |
|---|---|---|
| H3N2 birth cohort | Experimental | The H3N2 cohort consists of participants born between 1968-1977. Receives: Biological: FLUARIX QUADRIVALENT |
| H1N1 birth cohort | Experimental | The H1N1 cohort consists of participants born between 1948-1957. Receives: Biological: FLUARIX QUADRIVALENT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants Achieving Seroprotection Against Each Strain
Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response. Seroprotection is defined as a titer of ≥ 40.
Measured: 28 days after vaccination
The Number of Participants Achieving Seroconversion Against Each Strain
Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response. Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10.
Measured: 28 days after vaccination
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
Measured: 28 days after vaccination
Secondary outcomes (7)
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response
Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by neutralizing antibody (NAb) response. The proportion of subjects achieving seroprotection (titer of ≥ 40) or seroconversion (four-fold rise in NAb post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10) against each strain will be assessed.
Measured: 28 days after vaccination
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
Measured: 28 days after vaccination
The Number of Participants Achieving Seroprotection Against Each Strain
Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response. Seroprotection is defined as a titer of ≥ 40.
Measured: 180 days after vaccination
The Number of Participants Achieving Seroconversion Against Each Strain
Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response. Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10.
Measured: 180 days after vaccination
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
Measured: 180 days after vaccination
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response
Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by NAb antibody response.
Measured: 180 days after vaccination
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
Measured: 180 days after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2018
- Study start22 Oct 2018
- Primary completion20 Jun 2020
- Study completion20 Jun 2020
Why it stopped: The study closed prior to completing year 3 of the study due to the COVID-19 pandemic.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nadine Rouphael, Emory University
- Investigators
- Nadine Rouphael, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03686514
- Sponsor's protocol ID
- IRB00106407
- Acronym
- FLU2
- Status last verified
- Jun 2022
- First submitted
- 25 Sep 2018
- Last updated
- 13 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sherman AC, Lai L, Bower M, Natrajan MS, Huerta C, Karmali V, Kleinhenz J, Xu Y, Rouphael N, Mulligan MJ. The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination. Vaccines (Basel). 2020 Nov 7;8(4):663. doi: 10.3390/vaccines8040663.
PubMed 33171854
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics
- ClinicalTrials.gov ID
- NCT03686514
- Acronym / sponsor ID
- FLU2 / IRB00106407
- Conditions
- Influenza
- Keywords
- Flu vaccine, Influenza vaccine, Immune response, Influenza strain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study closed prior to completing year 3 of the study due to the COVID-19 pandemic.
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 22 Oct 2018 (actual)
- Primary completion
- 20 Jun 2020 (actual)
- Study completion
- 20 Jun 2020 (actual)
- First posted
- 27 Sep 2018 (actual)
- Results
- Posted 13 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system.
Detailed description
Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated 3-5 million cases of severe illness, and 250,000 to 500,000 deaths worldwide each year. In the United States, the Centers for Disease Control and Prevention (CDC) reports that influenza has resulted in 9.2-35.6 million illnesses with 12,000-56,000 deaths annually since 2010. There is an urgent need to better understand the immunologic responses to current licensed vaccines in order to develop a more effective vaccine that does not rely on annual updates, provides broad protection, and is durable; i.e., a universal influenza vaccine.
The immune response to the influenza vaccine is affected by many parameters, including prior imprinting to a specific influenza strain based on birth cohort, as well as prior influenza vaccination. The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses (IAVs) and two influenza B viruses (IBVs). The approved seasonal influenza vaccine will be given for each season of influenza: 2018-2019, 2019-2020, and 2020-2021.
This study is a prospective pilot study conducted over the course of three years (with three specific influenza seasons studied). For each year (2018-2019, 2019-2020, and 2020-2021), two cohorts of 10 participants each, who are in good health and meet all eligibility criteria, will be recruited. The influenza A virus subtype H3N2 cohort (N=30 total, 10 per year) will consist of participants born between 1968-1977, and the influenza A virus subtype H1N1 cohort (N=30 total, 10 per year) will consist of participants born between 1948-1957. Each participant will make a total of six visits to the Hope Clinic. Day 1 will include the informed consent process, and screening to ensure the subject meets all inclusion criteria and meets no exclusion criteria. For the consenting and eligible subject, the visit will also include pre-vaccination phlebotomy for baseline immunogenicity laboratory assays. After baseline sample collection, the participants will receive the FDA-approved seasonal influenza vaccine. Subsequent study visits up to 180 days post-vaccination will include collection for immunogenicity assays.
This study is not powered to test a formal null hypothesis. Rather, it is a hypothesis-generating investigation that will hopefully lead to larger trials based on the findings. The study will be conducted over the course of three years to increase the total sample population size and to validate the findings over different influenza seasons.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H3N2 birth cohort | Experimental | Biological: FLUARIX QUADRIVALENTThe H3N2 cohort consists of participants born between 1968-1977. |
| H1N1 birth cohort | Experimental | Biological: FLUARIX QUADRIVALENTThe H1N1 cohort consists of participants born between 1948-1957. |
Who may qualify
- Ages
- 42 to 71 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Capable of informed consent and provision of written informed consent before any study procedures.
- Capable of attending all study visits according to the study schedule.
- Males or females born between 1968-1977 or 1948-1957.
- Are in good health, as determined by medical history and targeted physical exam related to this history.
- Oral temperature is less than 38 degrees Celsius.
Key exclusion criteria (14 listed)
- Have an acute illness within 72 hours before vaccination.
- Have any condition that, in the opinion of the principal investigator, would place the subject at an unacceptable risk of harm or confound the interpretation of the study results.
- Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination.
- Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
- Have known HIV, hepatitis B, or hepatitis C infection.
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 |
|---|---|---|
| FLUARIX QUADRIVALENTThe FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses. | Biological | H1N1 birth cohort, H3N2 birth cohort |
Primary outcome
The Number of Participants Achieving Seroprotection Against Each Strain
Time frame: 28 days after vaccination
Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response. Seroprotection is defined as a titer of ≥ 40.
The Number of Participants Achieving Seroconversion Against Each Strain
Time frame: 28 days after vaccination
Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response. Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10.
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
Time frame: 28 days after vaccination
The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
7 secondary outcomes
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response
Time frame: 28 days after vaccination
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
Time frame: 28 days after vaccination
The Number of Participants Achieving Seroprotection Against Each Strain
Time frame: 180 days after vaccination
The Number of Participants Achieving Seroconversion Against Each Strain
Time frame: 180 days after vaccination
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
Time frame: 180 days after vaccination
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response
Time frame: 180 days after vaccination
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
Time frame: 180 days after vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33171854Sherman AC, Lai L, Bower M, Natrajan MS, Huerta C, Karmali V, Kleinhenz J, Xu Y, Rouphael N, Mulligan MJ. The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination. Vaccines (Basel). 2020 Nov 7;8(4):663. doi: 10.3390/vaccines8040663.
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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.
Nadine Rouphael, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing FLUARIX QUADRIVALENT in people with Influenza, run by Emory University 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 8 inclusion and 14 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: stopped early, as of the sponsor's last update on 13 Jul 2022. 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 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 13 Jul 2022). 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?
The Number of Participants Achieving Seroprotection Against Each Strain (time frame: 28 days after vaccination). The study lists 3 primary outcomes in all. 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 NCT03686514, 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 13 Jul 2022.