Study of Single Dose GHB16L2 Trivalent Influenza Vaccine in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this phase I/II trial is to evaluate safety and tolerability of a single dose of GHB16L2 administered by liquid nasal spray for vaccination against seasonal influenza virus infection. It is also performed to assess immunogenicity and pharmacokinetics (shedding).

Detailed Description
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GHB16L2 intends to provide a novel vaccination for influenza virus infection. 80 healthy volunteers will be included at a ratio of 1:1 for GHB16L2 or placebo. GHB16L2 will be administered once on day 1. Follow-up visits will be performed on days 2, 8 and 29.

Official Title
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Randomised, Double-blind, Placebo-controlled, Phase I/II Study of Single Dose GHB16L2 Trivalent Influenza Vaccine in Healthy Adults

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: GHB16L2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers, 18-60 years Seronegative for one or two of the applied vaccine strains Low antibody titres for H1N1v Written informed consent to participate in this study For female volunteers of childbearing potential, provision of a history and current use of reliable contraceptive practices Exclusion Criteria: Acute febrile illness (>37.3°C) Signs of acute or chronic upper or lower tract respiratory illnesses History of severe atopy Seasonal influenza vaccination in 2008/2009 and/or later seasons and/or pandemic influenza vaccination at any time Fever ≥38.0°C in the time period between the pre-screening visit and day 1 Known increased tendency of nose bleeding Volunteers with clinically relevant abnormal paranasal anatomy Volunteers with clinically relevant abnormal laboratory values In female volunteers of childbearing potential, a positive urine pregnancy test Simultaneous treatment with immunosuppressive drugs incl. Corticosteroids (≥2 weeks) within 4 weeks prior to study medication application Clinically relevant history of renal, hepatic, GI, cardiovascular, haematological, skin, endocrine, neurological or immunological diseases History of leukaemia or cancer HIV or Hepatitis B or C seropositivity Volunteers who underwent rhino or sinus surgery, or surgery of another traumatic injury of the nose within 30 days prior to application of study medication Volunteers who have received antiviral drugs, treatment with immunoglobulins or blood transfusions, or an investigational drug within 4 weeks prior to study medication application Volunteers who have received anti-inflammatory drugs 2 days prior to study medication application Volunteers who are not likely to cope with the requirements of the study or with a significant physical or mental condition that may interfere with the completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SPGNH buffer<br>SPGNH buffer administration by liquid nasal spray | Biological: Placebo<br>* SPGNH buffer<br>|
| Experimental: GHB16L2<br>Dose level  7.0 log10 fTCID50/strain/person | Biological: GHB16L2<br>* A/Brisbane/59/07(H1N1)-like delNS1, A/Brisbane/10/07(H3N2)-like delNS1, B/Florida/04/06-like delNS1 virus reassortants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events |  | From baseline to 30 days after end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates at day 29 | Seroconversion rates for HAI, MNA, IgA and IgG | At day 29 (end of study) | 
| Determination of the presence of GHB16L2 in mucosal samples (viral recovery/shedding) |  | 1 week post immunisation | 
| Immune response factor at day 29 | Immune response factors for HAI, MNA, IgA and IgG | At day 29 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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live attenuated flu vaccines, influenza A (H1N1), intranasal application, replication-deficient influenza virus