Dose Finding Study of Single Dose GHB11L1 in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this phase IIa trial is to evaluate the immunogenicity of a single dose of GHB11L1 administered by liquid nasal spray for vaccination against influenza A (H1N1) virus. This study is also performed to assess safety, tolerability and pharmacokinetics (shedding) of a single dose of GHB11L1 administered by liquid nasal spray.

Detailed Description
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GHB11L1 intends to provide a novel vaccination for influenza virus infection. 48 healthy volunteers will be included in this phase IIa study investigating three dose levels. 16 subjects will be randomised at a ratio of 3:1 for GHB11L1 or placebo. Healthy male volunteers, 18-50 years of age and seronegative with respect to the applied virus antigens (antibody titers <1:10 detected) will be randomised. GHB11L1 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 IIa Dose Finding Study of Single Dose GHB11L1 in Healthy Adults

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: GHB11L1
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers, 18-50 years Seronegative for H1N1 (Influenza A/Brisbane/59/07 antibody titres <1:10 detected in haemagglutination inhibition assay) Written informed consent to participate in this study Exclusion Criteria: Acute febrile illness (>37.0°C) Signs of acute or chronic upper or lower tract respiratory illnesses (sneezing, cough, tonsillitis, otitis etc.) History of severe atopy Seasonal influenza vaccination in 2007/2008 and/or later seasons and/or pandemic influenza vaccination at any time Known increased tendency of nose bleeding Volunteers with clinically relevant abnormal paranasal anatomy Volunteers with clinically relevant abnormal laboratory values 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 four 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: 50 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Experimental: GHB11L1<br>Dose levels: 6.0 log10 TCID50/volunteer, 6.5 log10 TCID50/volunteer and 7.0 log10 TCID50/volunteer | Biological: GHB11L1<br>* GHB11L1 administration by liquid nasal spray at doses of 6.0 log10, 6.5 log10 and 7.0 log10 TCID50/volunteer<br>* Other names: A/Brisbane/59/07(H1N1)-like delNS1 virus reassortant;|
| Placebo Comparator: SPGN buffer<br>SPGN buffer administration by liquid nasal spray | Biological: Placebo<br>* SPGN buffer<br>* Other names: SPGN buffer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic immune response |  | From baseline to day 29 (end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical signs and symptoms, laboratory tests Pharmacokinetics: qualitative assessment of viral recovery (shedding) in nasal mucosal samples. |  | From written informed consent to 30 days after 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