Randomized, Double-blind, Placebo-controlled, Phase I Dose-escalation Study of Single Dose GHB01L1 in Healthy Volunteers (GHBCS-01)

This study has been completed.
Sponsor:
Information provided by:
AVIR Green Hills Biotechnology AG
ClinicalTrials.gov Identifier:
NCT00724997
First received: July 28, 2008
Last updated: December 7, 2009
Last verified: December 2009

July 28, 2008
December 7, 2009
March 2007
July 2008   (final data collection date for primary outcome measure)
The primary objective of safety and tolerability of GHB01L1 administered as single dose intranasal aerosol will be evaluated by clinical signs and symptoms as well as laboratory tests. [ Time Frame: Beginning with signing Informed Consent through 30 days after study end ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00724997 on ClinicalTrials.gov Archive Site
Local immune response: IgA and cytokines response in nasal mucosal samples. Systemic Immune response: HAI, MNA and IgG assessment in serum samples. Pharmacokinetics: qualitative assessment of viral recovery (shedding) in nasal mucosal samples. [ Time Frame: Samples are collected at baseline and at several time points till day 29 (end of study) ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Randomized, Double-blind, Placebo-controlled, Phase I Dose-escalation Study of Single Dose GHB01L1 in Healthy Volunteers
Randomized, Double-blind, Placebo-controlled, Phase I Dose-escalation Study of Single Dose GHB01L1 in Healthy Volunteers

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Seasonal Human Influenza
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
    dose level I: 6.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
    Intervention: Biological: GHB01L1
  • cohort II
    dose level II: 6.7 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
    Intervention: Biological: GHB01L1
  • cohort III
    dose level III: 7.0 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
    Intervention: Biological: GHB01L1
  • cohort IV
    dose level IV: 7.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
    Intervention: Biological: GHB01L1
  • cohort V
    dose level V: 7.7 log10 TCID50/volunteer, 16 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
    Intervention: Biological: GHB01L1
Morokutti A, Muster T, Ferko B. Intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal IgA antibodies in humans. Vaccine. 2014 Apr 7;32(17):1897-900. doi: 10.1016/j.vaccine.2014.02.009. Epub 2014 Feb 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
August 2008
July 2008   (final data collection date for primary outcome measure)

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
Male
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT00724997
GHB-CS01, EudraCT 2006-001176-20
Yes
Thomas Muster PhD, CEO/CSO, AVIR Green Hills Biotechnology AG
AVIR Green Hills Biotechnology AG
Not Provided
Principal Investigator: Volker Wacheck, MD Medical University Vienna
AVIR Green Hills Biotechnology AG
December 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP