InfluenzaNCT02557802
T-cell Diversity Following Intranasal and Intramuscular Vaccines
A study testing Fluenz Tetra and Fluarix Tetra in people with Influenza, run by University of Surrey at 1 site in United Kingdom.
Trial summary
The investigators will explore in an experimental medicine healthy human model of immunisation, whether switching the route of sequential administration of licensed influenza vaccines can result in an immune response that is broader in its ability to recognise different substrains of influenza viruses. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Fluenz Tetra and Fluarix Tetra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2015to Jan 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female participants aged 18-55 years inclusive at visit
- Available for follow-up for the duration of the study.
- If fertile female, willing to undergo urine pregnancy tests prior to immunisations.
- Able to read and understand the Informed Consent Form (ICF), and understand study procedures and has signed the ICF.
- Has not received any influenza vaccine in the 2015/16 influenza season.
Who cannot join
- Any contraindication to receiving the study vaccines as detailed in the Summary of Product Characteristics.
- Clinically significant medical condition that would interfere with study endpoints as determined by the study physician at screening.
- Use of immunosuppressive/immunomodulating drugs orally or parenterally within 6 months of visit 1 or during the study follow-up period. Topical, inhaled and intranasal preparations are not excluded.
- Currently participating in another clinical study with an investigational or non-investigational drug or device, or has participated in another clinical study within the 3 months preceding Visit 1.
- Any condition that, in the investigator's opinion, compromises the participant's ability to meet protocol requirements or to complete the study.
- Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
- Positive pregnancy test on the day of immunisation.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Surrey Clinical Research Centre
Guildford, Surrey, GU2 7XP
About this study
Official title: Breadth of T-cell Responses After Heterologous Route Immunological Prime-boost Using Influenza Antigens as a Model System
The investigators will explore in an experimental medicine healthy human model of immunisation, whether switching the route of sequential administration of licensed influenza vaccines can result in an immune response that is broader in its ability to recognise different substrains of influenza viruses. The investigators will do this by initially giving an immunisation with a nasal or an injected vaccine, and then switching subjects over to receive a second dose one month later (when the cellular component of immunity will have matured) via the opposite route (nasal->injected or injected->nasal). The investigators will use research assays that can map the different parts of the influenza virus that the vaccinated person's immune cells recognise at baseline, after the first immunisation, and then again after the second, to see if the breadth of the recognition has broadened to include new strains or virus components. Should this pilot study give an indication that the breadth has widened (rather than just a further boost to the same responses seen after the first immunisation) it will provide justification for a larger study in which statistical significance may be powered for observed changes.
The study is funded by ADITEC, which is a collaborative research programme that aims to accelerate the development of novel and powerful immunisation technologies for the next generation of human vaccines.
Read the detailed description
This study is an Open-label, randomised, exploratory, hypothesis generating study.
Each participant will participate in the study for approximately two months. Recruitment aims to begin, on receipt of a favourable opinion from the ethics committee, in October/ November 2015, during the flu season.
There will be three outpatient visits during the study: Visit 1 will be screening and immunisation, Visit 2 will be immunisation, and Visit 3 will be an outpatient follow-up. All visits will take place at the Surrey Clinical Research Centre.
Written informed consent will be obtained after a participant is informed of the nature, significance, implications and risks of the study and prior to the commencement of any study specific procedures.
There will be two immunisations for each participant: one at Day 0 (visit 1) and the other at Day 28 (visit 2). After screening participants will be randomised to one of two treatment groups (n=15 in each group) and will receive a dose of the vaccine at the recommended dose level, according to the Summary of Product Characteristics, in the following orders:
Group A: Intranasal spray at day 0 followed by intramuscular injection at day 28
Group B: Intramuscular injection at day 0 followed by intranasal spray at day 28
Visit 1 (Day 0): At this visit informed consent will be obtained, demographic data and medical history recorded. Concomitant medications will be reviewed and a symptoms-directed physical examination will take place. Heart rate, blood pressure and oral temperature will also be recorded. A pregnancy test (urine) will be conducted where indicated. Participants will be assessed for inclusion and exclusion criteria. At this point if the participant is eligible they will be randomised to group A or B. Blood samples will be taken for serum and PBMC and they will be given the immunisation of either the nasal spray or the intramuscular injection depending on which group they are in.
Immunisation will be postponed if the person is suffering from an acute illness with an oral temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral temperature is <38°C. Subsequent visits will be delayed by the same duration.
Visit 2 (Day 28): At visit two, medical history will be updated and there will be a review of concomitant medications. A symptoms-directed physical examination will also take place. Heart rate, blood pressure and oral temperature will also be recorded. A pregnancy test (urine) will be conducted where indicated. Participants will be again be assessed for inclusion and exclusion criteria. Blood samples will be taken for serum and PBMC and they will be given the immunisation of either the nasal spray or the intramuscular injection depending on which group they are in
Immunisation will be postponed if the person is suffering from an acute illness with an oral temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral temperature is <38°C.
A visit window of -3 days or +7 days is acceptable for Visit 2 but should be avoided wherever possible and used only in a situation where a sample would otherwise be lost. Visit 3 should be rescheduled to maintain 28 days between visits.
Visit 3 (Day 56): At visit 3 there will be a review on concomitant medications and blood samples will be taken for serum and PBMC.
A visit window of -3 and +14 days is acceptable for Visit 3 but should be avoided wherever possible and used only in a situation where a sample would otherwise be lost. If participants cannot attend within this window then samples should be collected on the earliest date possible AFTER the expected visit window. These samples may be tested but will not be per protocol.
- Conditions
- Influenza
- Being tested
- Fluenz Tetra, Fluarix Tetra
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluenz TetraBiological
Intranasal spray, 0.2 ml dose
Fluarix TetraBiological
Intramuscular injection, 0.5 ml dose
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Nasal spray at day 0, intramuscular injection at day 28 Receives: Biological: Fluenz Tetra; Biological: Fluarix Tetra |
| Group B | Experimental | Intramuscular injection at day 0, nasal spray at day 28 Receives: Biological: Fluenz Tetra; Biological: Fluarix Tetra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Breadth of T-cell responses
Breadth of T-cell responses to influenza antigens measured by increases in frequency and phenotype of T cells synthesising or secreting cytokines, or proliferating in response to in vitro stimulation with influenza antigens.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2015 (estimated)
- Study startOct 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- 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 N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Surrey
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Lewis, Principal investigator, University of Surrey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02557802
- Sponsor's protocol ID
- CRC306C
- Status last verified
- Jan 2016
- First submitted
- 22 Sep 2015
- Last updated
- 26 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breadth of T-cell Responses After Heterologous Route Immunological Prime-boost Using Influenza Antigens as a Model System
- ClinicalTrials.gov ID
- NCT02557802
- Acronym / sponsor ID
- CRC306C
- Conditions
- Influenza
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of SurreyUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 23 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will explore in an experimental medicine healthy human model of immunisation, whether switching the route of sequential administration of licensed influenza vaccines can result in an immune response that is broader in its ability to recognise different substrains of influenza viruses. The investigators will do this by initially giving an immunisation with a nasal or an injected vaccine, and then switching subjects over to receive a second dose one month later (when the cellular component of immunity will have matured) via the opposite route (nasal->injected or injected->nasal). The investigators will use research assays that can map the different parts of the influenza virus that the vaccinated person's immune cells recognise at baseline, after the first immunisation, and then again after the second, to see if the breadth of the recognition has broadened to include new strains or virus components. Should this pilot study give an indication that the breadth has widened (rather than just a further boost to the same responses seen after the first immunisation) it will provide justification for a larger study in which statistical significance may be powered for observed changes.
The study is funded by ADITEC, which is a collaborative research programme that aims to accelerate the development of novel and powerful immunisation technologies for the next generation of human vaccines.
Detailed description
This study is an Open-label, randomised, exploratory, hypothesis generating study.
Each participant will participate in the study for approximately two months. Recruitment aims to begin, on receipt of a favourable opinion from the ethics committee, in October/ November 2015, during the flu season.
There will be three outpatient visits during the study: Visit 1 will be screening and immunisation, Visit 2 will be immunisation, and Visit 3 will be an outpatient follow-up. All visits will take place at the Surrey Clinical Research Centre.
Written informed consent will be obtained after a participant is informed of the nature, significance, implications and risks of the study and prior to the commencement of any study specific procedures.
There will be two immunisations for each participant: one at Day 0 (visit 1) and the other at Day 28 (visit 2). After screening participants will be randomised to one of two treatment groups (n=15 in each group) and will receive a dose of the vaccine at the recommended dose level, according to the Summary of Product Characteristics, in the following orders:
Group A: Intranasal spray at day 0 followed by intramuscular injection at day 28
Group B: Intramuscular injection at day 0 followed by intranasal spray at day 28
Visit 1 (Day 0): At this visit informed consent will be obtained, demographic data and medical history recorded. Concomitant medications will be reviewed and a symptoms-directed physical examination will take place. Heart rate, blood pressure and oral temperature will also be recorded. A pregnancy test (urine) will be conducted where indicated. Participants will be assessed for inclusion and exclusion criteria. At this point if the participant is eligible they will be randomised to group A or B. Blood samples will be taken for serum and PBMC and they will be given the immunisation of either the nasal spray or the intramuscular injection depending on which group they are in.
Immunisation will be postponed if the person is suffering from an acute illness with an oral temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral temperature is <38°C. Subsequent visits will be delayed by the same duration.
Visit 2 (Day 28): At visit two, medical history will be updated and there will be a review of concomitant medications. A symptoms-directed physical examination will also take place. Heart rate, blood pressure and oral temperature will also be recorded. A pregnancy test (urine) will be conducted where indicated. Participants will be again be assessed for inclusion and exclusion criteria. Blood samples will be taken for serum and PBMC and they will be given the immunisation of either the nasal spray or the intramuscular injection depending on which group they are in
Immunisation will be postponed if the person is suffering from an acute illness with an oral temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral temperature is <38°C.
A visit window of -3 days or +7 days is acceptable for Visit 2 but should be avoided wherever possible and used only in a situation where a sample would otherwise be lost. Visit 3 should be rescheduled to maintain 28 days between visits.
Visit 3 (Day 56): At visit 3 there will be a review on concomitant medications and blood samples will be taken for serum and PBMC.
A visit window of -3 and +14 days is acceptable for Visit 3 but should be avoided wherever possible and used only in a situation where a sample would otherwise be lost. If participants cannot attend within this window then samples should be collected on the earliest date possible AFTER the expected visit window. These samples may be tested but will not be per protocol.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: Fluenz Tetra, Biological: Fluarix TetraNasal spray at day 0, intramuscular injection at day 28 |
| Group B | Experimental | Biological: Fluenz Tetra, Biological: Fluarix TetraIntramuscular injection at day 0, nasal spray at day 28 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male or female participants aged 18-55 years inclusive at visit
- Available for follow-up for the duration of the study.
- If fertile female, willing to undergo urine pregnancy tests prior to immunisations.
- Able to read and understand the Informed Consent Form (ICF), and understand study procedures and has signed the ICF.
- Has not received any influenza vaccine in the 2015/16 influenza season.
Key exclusion criteria (7 listed)
- Any contraindication to receiving the study vaccines as detailed in the Summary of Product Characteristics.
- Clinically significant medical condition that would interfere with study endpoints as determined by the study physician at screening.
- Use of immunosuppressive/immunomodulating drugs orally or parenterally within 6 months of visit 1 or during the study follow-up period. Topical, inhaled and intranasal preparations are not excluded.
- Currently participating in another clinical study with an investigational or non-investigational drug or device, or has participated in another clinical study within the 3 months preceding Visit 1.
- Any condition that, in the investigator's opinion, compromises the participant's ability to meet protocol requirements or to complete the study.
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 |
|---|---|---|
| Fluenz TetraIntranasal spray, 0.2 ml dose | Biological | Group A, Group B |
| Fluarix TetraIntramuscular injection, 0.5 ml dose | Biological | Group A, Group B |
Primary outcome
Breadth of T-cell responses
Time frame: 8 months
Breadth of T-cell responses to influenza antigens measured by increases in frequency and phenotype of T cells synthesising or secreting cytokines, or proliferating in response to in vitro stimulation with influenza antigens.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2016.
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.
David Lewis principal investigator
University of Surrey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fluenz Tetra and Fluarix Tetra in people with Influenza, run by University of Surrey at 1 site in United Kingdom.
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 5 inclusion and 7 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 26 Jan 2016. 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 Kingdom. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Breadth of T-cell responses (time frame: 8 months). 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 26 Jan 2016.