Dose Finding Study of Single Dose GHB11L1 in Healthy Adults (GHB-CS07)

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.

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.

• Biological: GHB11L1
  GHB11L1 administration by liquid nasal spray at doses of 6.0 log10, 6.5 log10 and 7.0 log10 TCID50/volunteer
  Other Name: A/Brisbane/59/07(H1N1)-like delNS1 virus reassortant
• Biological: Placebo
  SPGN buffer
  Other Name: SPGN buffer

• Experimental: GHB11L1
  Dose levels: 6.0 log10 TCID50/volunteer, 6.5 log10 TCID50/volunteer and 7.0 log10 TCID50/volunteer
  Intervention: Biological: GHB11L1
• Placebo Comparator: SPGN buffer
  SPGN buffer administration by liquid nasal spray
  Intervention: Biological: Placebo

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