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

December 7, 2009 updated by: AVIR Green Hills Biotechnology AG

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, A-1090
        • Medical University Vienna, Vienna General Hospital, Dpmt. of Clinical Pharmacology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: cohort I
dose level I: 6.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
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)
Other: cohort II
dose level II: 6.7 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
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)
Other: cohort III
dose level III: 7.0 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
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)
Other: cohort IV
dose level IV: 7.4 log10 TCID50/volunteer, 8 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
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)
Other: cohort V
dose level V: 7.7 log10 TCID50/volunteer, 16 volunteers randomized at a ratio of 6:2 for GHB01L1 or placebo
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Beginning with signing Informed Consent through 30 days after study end

Secondary Outcome Measures

Outcome Measure
Time Frame
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)
Samples are collected at baseline and at several time points till day 29 (end of study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AVIR Green Hills Biotechnology AG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

July 28, 2008

First Submitted That Met QC Criteria

July 28, 2008

First Posted (Estimate)

July 30, 2008

Study Record Updates

Last Update Posted (Estimate)

December 8, 2009

Last Update Submitted That Met QC Criteria

December 7, 2009

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GHB-CS01
  • EudraCT 2006-001176-20

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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