Official Title

Randomized, Double-blind, Placebo-controlled, Phase I Dose-escalation Study of Single Dose GHB01L1 in Healthy Volunteers
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Intervention/Treatment

    ghb01l1 ...
  • Study Participants

    48
The purpose of this phase I trial is to evaluate safety and tolerability of GHB01L1 administered as single dose intranasal aerosol for vaccination against influenza A (H1N1) virus.

This study is performed further to assess local and systemic immune response and to analyse pharmacokinetics (shedding) of a single dose GHB01L1 aerosol administered intranasally.
GHB01L1 intends to provide a novel vaccination for influenza virus infection. Data indicate that the GHB01L1 virus is a promising, safe and immunogenic vaccine candidate with a high protection efficacy against the pathogenic wild-type virus challenge.

48 healthy volunteers will be included in a phase I dose escalation study investigating five dose levels. 8 subjects per each of the five dose levels and additional 8 subjects at the highest dose level respectively the maximum tolerated dose level will be randomized at a ratio of 6:2 for GHB01L1 or placebo according to a fixed dose escalation plan.

After all subjects of one dose level have been treated and observed for the safety observation period of one week, an interim safety review will be performed by an Expert Committee. The Expert Committee will review any occurred adverse event and will decide on dose escalation to the next dose level.

Only male healthy volunteers aged 18-50 and seronegative with respect to the applied virus antigens (with antibody titers <1:10 detected in hemagglutination inhibition assay) will be randomized.

GHB01L1 will be administered once on day 1. After a 3 days inpatient period follow-up visits will be performed on day 4, 5, 8, 15 and the study will be terminated on day 29.
Study Started
Mar 31
2007
Primary Completion
Jul 31
2008
Study Completion
Aug 31
2008
Last Update
Dec 08
2009
Estimate

Biological GHB01L1

Study medication administered as a single intranasal aerosol (520ul) at doses of 6.4 log10, 6.7 log10, 7.0 log10, 7.4 log10 and 7.7 log10 TCID50/volunteer

  • Other names: A/New Caledonia/20/99 (H1N1) -like delNS1 virus, GHB01NC(H1N1)

cohort I Other

dose level I: 6.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo

cohort II Other

dose level II: 6.7 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo

cohort III Other

dose level III: 7.0 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo

cohort IV Other

dose level IV: 7.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo

cohort V Other

dose level V: 7.7 log10 TCID50/volunteer, 16 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo

Criteria

Inclusion Criteria:

Healthy male volunteers, 18-50 years
Immune status: seronegative with respect to the applied virus antigens with antibody titres <1:10 detected in the HAI assay with the corresponding antigens)
Written informed consent to participate in this study

Exclusion Criteria:

Acute febrile illness (>37.3°C)
Signs of acute or chronic upper or lower tract respiratory illnesses (sneezing, cough, tonsillitis, otitis etc.)
History of severe atopy
Seasonal influenza vaccination 2005/2006, 2006/2007 and/or 2007/2008 and/or pandemic influenza vaccination against H5N1
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
No Results Posted