HealthyNCT01771367
Training Study to Characterize Biomarkers to Flu Vaccines
A study testing Fluad and Agrippal in people with Healthy, run by University of Surrey at 1 site in United Kingdom.
Trial summary
It is thought that vaccines trigger innate inflammatory responses to induce antigen-specific adaptive immunity (the desired effect), but excessive inflammation may lead to serious inflammatory complications or unwanted side effects. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Fluad and Agrippal
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2013to Nov 2013
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects aged 18-45 years inclusive. Randomisation will ensure equal numbers of men and women.
- The subject is, in the opinion of the investigator, healthy on the basis of medical history, vital signs, and the results of routine laboratory tests with no active disease process that could interfere with the study endpoints.
- Body Mass Index ≥18.5 and <29.5
- The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
- The subject has signed the ICF.
- Available for follow-up for the duration of the study.
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- Agree to abstain from donating blood during and for three months after the end of their participation in the study, or longer if necessary.
- If heterosexually active female, willing to use an effective method of contraception with partner (oral contraceptive pill; intrauterine device; injectable or implanted contraceptive; condoms incorporating spermicide if using these; physiological or anatomical sterility) from 30 days prior to, and 3 months after, vaccination. Willing to undergo urine pregnancy tests prior to vaccination and blood pregnancy test at screening and final follow up.
- The subject self-reports at screening that for the past month they have had regular sleep pattern with bedtime occurring between 22:00 and 01:00 h.
- The subject has venous access sufficient to allow blood sampling as per the protocol.
Who cannot join
- Significant dietary restrictions (e.g. vegan, lactose intolerant, but vegetarian acceptable) or life-threatening food allergies (e.g. anaphylaxis-related nut allergies).
- Pregnant or lactating at any point during the study from screening to final follow up.
- As subjects must be eligible to be randomised to any of the treatment groups they must fulfil the vaccine contraindications eligibility for both group A \& B:
- Hypersensitivity to the active components of FLUAD, any of the excipients, eggs, chicken proteins, kanamycin and neomycin sulphate, formaldehyde, and cetyltrimetholammonium bromide or those who have had a previous life-threatening reaction to previous influenza vaccinations.
- Hypersensitivity to the active substances of Agrippal, to any excipients and to residues such as eggs and chicken proteins including ovalbumin.
- Presence of primary or acquired immunodeficiency states with a total lymphocyte count less than 1,200 per mm3 or presenting other evidence of lack of cellular immune competence e.g. leukaemias, lymphomas, blood dyscrasias, or patients receiving immunosuppressive therapy (including regular use of oral, inhaled, topical or parenteral corticosteroids).
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- Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1 (screening).
- Regular use of non-steroidal anti-inflammatory drugs (by any route of administration including topical) within 6 months of Visit 1 (screening) considered by the study physician as likely to interfere with immune responses.
- Receipt of a vaccine within 30 days of visit 2, or requirement to receive another vaccine within the study period.
- Presence of an acute severe febrile illness at time of immunisation.
- History of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1.
- Currently participating in another clinical study with an investigational or non-investigational drug or device, or has participated in a clinical trial within the 3 months preceding Visit 1.
- Any condition that, in the investigator's opinion, compromises the subject's ability to meet protocol requirements or to complete the study.
- Receipt of blood products or immunoglobin, or blood donation, within 3 months of screening.
- Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
- An average weekly alcohol intake that exceeds 14 or 21 units per week for females and males, respectively (1 unit = 12 oz or 360ml of beer; 5oz or 150ml of wine; 1.5oz or 45ml of distilled spirits), or unwilling to stop alcohol consumption for each treatment period during the study.
- Currently smokes in excess of 5 cigarettes/day or use tobacco or nicotine substitutes (within the last 6 months of screening), or subjects unwilling to refrain from smoking or are unable to abide by Surrey CRC restrictions.
- Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120mg caffeine) of coffee, tea, cola, or other caffeinated beverages/food per day.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Surrey, (Surrey Clinical Research Centre)
Guildford, Surrey, GU2 7XP
About this study
Official title: A Clinical Study to Generate an Exploratory Training Set of Data Characterising Clinical Events, Physiological and Metabolic Responses, and Innate and Adaptive Immune Responses Following a Single Intramuscular Immunisation With Either "Fluad" or "Agrippal" Influenza Vaccines or Saline Placebo in Healthy Adults.
It is thought that vaccines trigger innate inflammatory responses to induce antigen-specific adaptive immunity (the desired effect), but excessive inflammation may lead to serious inflammatory complications or unwanted side effects. Currently there is a lack of reliable biomarkers (a measurable biological response that predicts something) able to predict severe inflammation and this has resulted in the development of several vaccines being terminated and the withdrawal of some licensed vaccines which were associated with inflammatory complications.
This study is part of the BIOVACSAFE project which is a 5-year 30 million Euro project funded by the Innovative Medicines Initiative. The project involves a series of clinical studies using licensed vaccines as benchmarks to generate clinical data on inflammation and identify biomarkers that can be used to predict acceptable reactogenicity. The target is to identify biomarkers that can predict the occurrence of beneficial and detrimental effects in response to a vaccine. Such biomarkers could be used in future vaccine development programs to optimise selection of vaccine candidates with a profile that will be unlikely to generate worrisome safety signals once they are in generalised use.
This study is one in a series of "training" studies which will each use different licensed vaccines that are prototypical representatives of a class of vaccine used in a particular population. Forty-eight subjects will be randomised into three groups to receive: a) Fluad (n=20), b) Agrippal (n=20), c) saline placebo (n=8). Following a screening visit, participants will undergo a seven-day residential visit which will include immunisation and intensive monitoring of physiological (e.g. heart rate, oral temperature, blood pressure) metabolic and immune (innate and adaptive) parameters. This visit will be followed up by four outpatient visits with further monitoring and blood samples.
- Conditions
- Healthy
- Being tested
- Fluad, Agrippal, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluadBiological
AgrippalBiological
PlaceboBiological
| Study group | Role | What they receive |
|---|---|---|
| Fluad | Active comparator | Participants receive one dose of Fluad vaccine. Receives: Biological: Fluad |
| Agrippal | Active comparator | Participants receive one dose of Agrippal vaccine. Receives: Biological: Agrippal |
| Placebo | Placebo comparator | Participants receive one dose of saline placebo. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline values of global gene expression in whole blood.
Measured: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 (Day 14), 5 (Day 21), 6 (Day 28).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionJun 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 49 participants (actual)
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
- NCT01771367
- Sponsor's protocol ID
- CRC305C
- Status last verified
- Dec 2013
- First submitted
- 15 Jan 2013
- Last updated
- 16 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Weiner J, Lewis DJM, Maertzdorf J, Mollenkopf HJ, Bodinham C, Pizzoferro K, Linley C, Greenwood A, Mantovani A, Bottazzi B, Denoel P, Leroux-Roels G, Kester KE, Jonsdottir I, van den Berg R, Kaufmann SHE, Del Giudice G. Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium. Sci Rep. 2019 Dec 30;9(1):20362. doi: 10.1038/s41598-019-56994-8.
PubMed 31889148Muturi-Kioi V, Lewis D, Launay O, Leroux-Roels G, Anemona A, Loulergue P, Bodinham CL, Aerssens A, Groth N, Saul A, Podda A. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review. PLoS One. 2016 Aug 4;11(8):e0157385. doi: 10.1371/journal.pone.0157385. eCollection 2016.
PubMed 27490698Spensieri F, Siena E, Borgogni E, Zedda L, Cantisani R, Chiappini N, Schiavetti F, Rosa D, Castellino F, Montomoli E, Bodinham CL, Lewis DJ, Medini D, Bertholet S, Del Giudice G. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans. PLoS One. 2016 Jun 23;11(6):e0157066. doi: 10.1371/journal.pone.0157066. eCollection 2016.
PubMed 27336786
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Generate an Exploratory Training Set of Data Characterising Clinical Events, Physiological and Metabolic Responses, and Innate and Adaptive Immune Responses Following a Single Intramuscular Immunisation With Either "Fluad" or "Agrippal" Influenza Vaccines or Saline Placebo in Healthy Adults.
- ClinicalTrials.gov ID
- NCT01771367
- Acronym / sponsor ID
- CRC305C
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of SurreyUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 18 Jan 2013 (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.
It is thought that vaccines trigger innate inflammatory responses to induce antigen-specific adaptive immunity (the desired effect), but excessive inflammation may lead to serious inflammatory complications or unwanted side effects. Currently there is a lack of reliable biomarkers (a measurable biological response that predicts something) able to predict severe inflammation and this has resulted in the development of several vaccines being terminated and the withdrawal of some licensed vaccines which were associated with inflammatory complications.
This study is part of the BIOVACSAFE project which is a 5-year 30 million Euro project funded by the Innovative Medicines Initiative. The project involves a series of clinical studies using licensed vaccines as benchmarks to generate clinical data on inflammation and identify biomarkers that can be used to predict acceptable reactogenicity. The target is to identify biomarkers that can predict the occurrence of beneficial and detrimental effects in response to a vaccine. Such biomarkers could be used in future vaccine development programs to optimise selection of vaccine candidates with a profile that will be unlikely to generate worrisome safety signals once they are in generalised use.
This study is one in a series of "training" studies which will each use different licensed vaccines that are prototypical representatives of a class of vaccine used in a particular population. Forty-eight subjects will be randomised into three groups to receive: a) Fluad (n=20), b) Agrippal (n=20), c) saline placebo (n=8). Following a screening visit, participants will undergo a seven-day residential visit which will include immunisation and intensive monitoring of physiological (e.g. heart rate, oral temperature, blood pressure) metabolic and immune (innate and adaptive) parameters. This visit will be followed up by four outpatient visits with further monitoring and blood samples.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fluad | Active comparator | Biological: FluadParticipants receive one dose of Fluad vaccine. |
| Agrippal | Active comparator | Biological: AgrippalParticipants receive one dose of Agrippal vaccine. |
| Placebo | Placebo comparator | Biological: PlaceboParticipants receive one dose of saline placebo. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy male or female subjects aged 18-45 years inclusive. Randomisation will ensure equal numbers of men and women.
- The subject is, in the opinion of the investigator, healthy on the basis of medical history, vital signs, and the results of routine laboratory tests with no active disease process that could interfere with the study endpoints.
- Body Mass Index ≥18.5 and <29.5
- The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
- The subject has signed the ICF.
Key exclusion criteria (18 listed)
- Significant dietary restrictions (e.g. vegan, lactose intolerant, but vegetarian acceptable) or life-threatening food allergies (e.g. anaphylaxis-related nut allergies).
- Pregnant or lactating at any point during the study from screening to final follow up.
- As subjects must be eligible to be randomised to any of the treatment groups they must fulfil the vaccine contraindications eligibility for both group A \& B:
- Presence of primary or acquired immunodeficiency states with a total lymphocyte count less than 1,200 per mm3 or presenting other evidence of lack of cellular immune competence e.g. leukaemias, lymphomas, blood dyscrasias, or patients receiving immunosuppressive therapy (including regular use of oral, inhaled, topical or parenteral corticosteroids).
- Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1 (screening).
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 |
|---|---|---|
| Fluad | Biological | Fluad |
| Agrippal | Biological | Agrippal |
| Placebo | Biological | Placebo |
Primary outcome
Change from baseline values of global gene expression in whole blood.
Time frame: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 (Day 14), 5 (Day 21), 6 (Day 28).
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 16 Feb 2015.
- Derived from this study: PubMed 31889148Weiner J, Lewis DJM, Maertzdorf J, Mollenkopf HJ, Bodinham C, Pizzoferro K, Linley C, Greenwood A, Mantovani A, Bottazzi B, Denoel P, Leroux-Roels G, Kester KE, Jonsdottir I, van den Berg R, Kaufmann SHE, Del Giudice G. Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium. Sci Rep. 2019 Dec 30;9(1):20362. doi: 10.1038/s41598-019-56994-8.
- Derived from this study: PubMed 27490698Muturi-Kioi V, Lewis D, Launay O, Leroux-Roels G, Anemona A, Loulergue P, Bodinham CL, Aerssens A, Groth N, Saul A, Podda A. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review. PLoS One. 2016 Aug 4;11(8):e0157385. doi: 10.1371/journal.pone.0157385. eCollection 2016.
- Derived from this study: PubMed 27336786Spensieri F, Siena E, Borgogni E, Zedda L, Cantisani R, Chiappini N, Schiavetti F, Rosa D, Castellino F, Montomoli E, Bodinham CL, Lewis DJ, Medini D, Bertholet S, Del Giudice G. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans. PLoS One. 2016 Jun 23;11(6):e0157066. doi: 10.1371/journal.pone.0157066. eCollection 2016.
- BIOVACSAFELink provided by the sponsor.
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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.
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 Fluad and Agrippal in people with Healthy, 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 10 inclusion and 18 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 16 Feb 2015. 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. Some participants in this study may receive a placebo. 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?
Change from baseline values of global gene expression in whole blood. (time frame: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 (Day 14), 5 (Day 21), 6 (Day 28).). 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 NCT01771367, which also lists 3 linked publications.
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 16 Feb 2015.