Influenza Vaccine Challenge Study in Healthy Subjects
|Influenza||Biological: Influenza vaccine (FLU-v) Biological: Placebo (adjuvant only)||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomised Double-blind, Placebo-controlled, Phase 1b Trial to Evaluate the Safety, Tolerability and Protective Efficacy of the Influenza Vaccine Candidate, FLU-v, in an Influenza Challenge Model|
- Adverse Events (AEs) [ Time Frame: Day -21 to Day 28 ]The primary safety endpoint for the vaccination phase of the study is the evaluation of all AEs occurring up to Day 28 (final follow-up). AE details will be collected by subject questioning and review of a subject self-assessment diary card (completed for Days -21 to -14) at the clinic visit on Day -2
- Safety of FLU-v [ Time Frame: Days -21 to 28 ]
The Safety of FLU-v will be assessed by recording:
Area under the curve (AUC) of composite symptom score in the 6 days after inoculation (Days 0 to 5 inclusive; Physical examination; Clinical chemistry, haematology and urinalysis; Vital signs (blood pressure (BP), heart rate (HR) and respiration rate (RR)); Electrocardiogram; Oral temperature; and Concomitant medications.
- Post-innoculation symptoms [ Time Frame: Days 0 to 28 ]
Exploratory Endpoints - Symptoms measured by:
Time to peak of composite symptom score, duration, and time to resolution of composite score from peak; Peak severity symptom composite score in the 6 days after inoculation; Duration of upper respiratory infection (URI) symptoms after influenza viral inoculation; Occurrence of URI symptoms 1) with and 2) without fever; and occurrence of any influenza-like illness with or without fever.
- Post-innoculation virology [ Time Frame: 6 days following inoculation ]
Exploratory endpoint - Virology will be measured by recording an analysing:
Area under the curve (AUC) of influenza viral shedding in the 6 days after inoculation; Time to peak of influenza viral shedding, duration, and time to resolution of influenza viral shedding from peak; Peak of influenza viral shedding in the 6 days after inoculation.
- Post-innoculation fever [ Time Frame: Days -21 to 28 ]
Exploratory endpoint - Post-innoculation fever will be assessed by:
Area under the curve (AUC)and peak of fever; Duration of fever, time to peak fever, and time from peak to resolution of fever; Occurrence and duration of clinical illness with and without documented fever; Total tissue count and total mucus weight; Total number of individual tissues and total mucous weights; and humoral and cell-mediated immune responses to vaccine, pre-influenza challenge.
- Protective Efficacy (PE) [ Time Frame: Day 1 to 5 post-viral challenge ]Protective Efficacy measured by the proportion of cases prevented by the vaccine relative to placebo (the difference in attack rate for placebo vaccinated minus FLU-v vaccinated subjects divided by the placebo vaccinated group attack rate).
|Study Start Date:||June 2010|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
|Experimental: FLU-v with adjuvant||
Biological: Influenza vaccine (FLU-v)
FLU-v (sterile lyophilised mixture of polypeptide T-cell epitope sequences) and adjuvant. Administered by single subcutaneous injection.
Placebo Comparator: Placebo
Adjuvant only placebo
Biological: Placebo (adjuvant only)
Single subcutaneous injection of adjuvant
The investigational influenza vaccine (FLU-v) contains multiple highly conserved T cell epitopes that are present on most influenza viruses, which have been identified as reactive in different human leukocyte antigen (HLA) populations; thus making it unlikely that anybody in the vaccinated population would be unable to mount an immune response to at least one of the epitopes contained in the vaccine.
In this study up to 44 will be vaccinated with the FLU-v experimental vaccine or a placebo in a 1:1 ratio. Volunteers will attend a screening visit, a vaccination visit, a 10-11 day overnight stay in a quarantine facility, and a follow-up visit to the P1 clinic.
Three weeks after being vaccinated with FLU-v or placebo, 30 volunteers will be taken to a Quarantine Unit to be exposed to the attenuated H3N2 study virus and then monitored by study physicians and nurses for a 10-11 day period. The other 14 volunteers will be held in reserve as back-ups. If fewer than 30 of the volunteers who travel to the Quarantine Unit are eligible to be exposed to the study virus, then volunteers who have been kept in reserve will be used.
Following discharge from the Quarantine Unit, volunteers will attend one study follow-up visit, 28 days after exposure to the study virus. Assessments will take place and samples will be taken from volunteers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01226758
|Retroscreen Virology Limited|
|London, United Kingdom, NW1 0NH|
|Principal Investigator:||Anthony Gilbert, MBBCh, MICR||Retroscreen Virology Limited|