Placebo Controlled Study to Generate Data Characterising Clinical Events, Physiological Responses and Immune Responses

NCT02523287 | Completed Phase 4

• 1 other identifier: BioVacSafe - Fluad
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this protocol is to generate a set of data that will be analysed by integrated systems biology approach, for validation in subsequent clinical trials or in animal models. 240 healthy participants (18-45y) will be enrolled, 228 will be administered a dose of Fluad on Day 0, 12 will receive a placebo on Day 0.

Conditions

Safety Markers of Adjuvanted Influenza Vaccine

Outcome Measures

Primary Outcomes (20)

• Frequency of local and systemic vaccine-related clinical events.

  At all time points from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in pulse.

  At all time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in haematology (blood counts and ESR) parameters.

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in global gene expression measured on whole blood samples.

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in metabolic gene expression and pathway activation measured on whole blood samples.

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in serum HAI titre in serum samples.

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation values of adaptive cellular immune response via enumeration of HA-specific CD4+ T cells expressing activation markers and/or cytokines following in vitro stimulation and analysis by flow cytometry

  At 7 days after vaccination

• Change from pre-immunisation baseline values in concentration of selected cytokines and acute phase proteins in serum samples

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in PBMC cytokine secretion, proliferation or surface markers in response to in vitro antigen stimulation.

  At selected time points from time of vaccination up to 28 days after vaccination

• Genetic testing of subject (only when deemed necessary: may be SNIP analysis or full genome analysis)

  Up to 2 years after vaccination

• Change from pre-immunisation baseline values in body temperature.

  At all time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in blood pressure.

  At all time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in creatinin

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in CRP

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in AST/ALT

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in albumin

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in eGFR

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in GGT

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in total protein

  At selected time points from time of vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in total prothrombin/fibrinogen

  At selected time points from time of vaccination up to 28 days after vaccination

Study Arms (4)

Fluad - 5 study visits (114 subjects)

ACTIVE COMPARATOR

0,5 ml adjuvanted, subunit seasonal trivalent influenza vaccine (2014-2015). Administration: Intramuscular, deltoid. 5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 21 (blood sampling).

Biological: Fluad

Fluad - 3 study visits (114 subjects)

ACTIVE COMPARATOR

0,5 ml adjuvanted, subunit seasonal trivalent influenza vaccine (2014-2015). Administration: Intramuscular, deltoid. 3 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 7 (blood sampling). On day 21 there's a phone call for safety follow-up.

Biological: Fluad

Saline - 5 study visits (6 subjects)

PLACEBO COMPARATOR

0,5 ml saline. Administration: Intramuscular, deltoid. 5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 21 (blood sampling).

Biological: Saline

Saline - 3 study visits (6 subjects)

PLACEBO COMPARATOR

0,5 ml saline. Administration: Intramuscular, deltoid. 3 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 7 (blood sampling). On day 21 there's a phone call for safety follow-up.

Biological: Saline

Interventions

Fluad BIOLOGICAL

Randomized assignment

Fluad - 3 study visits (114 subjects); Fluad - 5 study visits (114 subjects)

Saline BIOLOGICAL

Randomized assignment

Saline - 3 study visits (6 subjects); Saline - 5 study visits (6 subjects)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects aged 18-45 years inclusive.
• Male: Female ratio - Screening will ensure that no more than 2/3 of the population should be of either male or female
• The subject is, in the opinion of the investigator: healthy based on medical history and clinical exam, with no active disease process that could interfere with the study endpoints.
• Has a body Mass Index ≥18 and ≤30
• Is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
• The subject has signed the ICF.
• The subject is available for follow-up for the duration of the study.
• The subject agrees to abstain from donating blood during their participation in the study, or longer if necessary.
• If the subject is a heterosexually active female, she is 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 at screening.
• The subject has venous access sufficient to allow blood sampling as per the protocol.

You may not qualify if:

• Pregnant or lactating at any point during the study from screening to final follow up.
• 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.
• 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 or parenteral corticosteroids).
• Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1.
• Regular use of non-steroidal anti-inflammatory drugs (oral or parenteral route) within 6 months of Visit 1 considered by the study physician as likely to interfere with immune responses.
• Current intake of excessive amounts of alcohol and/or caffeine (as evaluated by the investigator) and not willing to adapt this use during the study period.
• Currently performing extreme physical activities (as evaluated by the investigator) and not willing to adapt this use during the study period.
• Receipt of a vaccine within 30 days of visit 1, or requirement to receive another vaccine within the study period.
• Vaccination with the 2014/2015 seasonal influenza vaccine and/or any other seasonal influenza vaccine within the last 6 months before the first study visit.
• Presence of an acute severe febrile illness at time of immunisation.
• History of alcohol, narcotic, benzodiazepine, rilatine, 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 Dutch or English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University of Surrey: collaborator
• Novartis Vaccines: collaborator
• Max Planck Institute for Infection Biology: collaborator
• deCODE genetics: collaborator
• VisMederi srl: collaborator
• GlaxoSmithKline: collaborator
• Innovative Medicines Initiative: collaborator

Study Sites (1)

Center for Vaccinology

Ghent, East-Flanders, 9000, Belgium

Location

Related Publications (1)

• Muturi-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.

  PMID: 27490698 DERIVED

MeSH Terms

Interventions

fluad vaccine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Geert Leroux-Roels, Prof,MD

  Center for Vaccinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: August 14, 2015
• Study Start: October 2, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

BE (1)