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

Primary Purpose

Seasonal Human Influenza

Status

Completed

Phase

Phase 1

Locations

Austria

Study Type

Interventional

Intervention

GHB01L1

About this trial

This is an interventional prevention trial for Seasonal Human Influenza focused on measuring live attenuated flu vaccines, Influenza A (H1N1), intranasally application, replication-deficient influenza virus

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Medical University Vienna, Vienna General Hospital, Dpmt. of Clinical Pharmacology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Other

Arm Label

cohort I

cohort II

cohort III

cohort IV

cohort V

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00724997

First Posted

July 28, 2008

Last Updated

December 7, 2009

Sponsor

AVIR Green Hills Biotechnology AG

1. Study Identification

Unique Protocol Identification Number

NCT00724997

Brief Title

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

Acronym

GHBCS-01

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2009

Overall Recruitment Status

Completed

Study Start Date

March 2007 (undefined)

Primary Completion Date

July 2008 (Actual)

Study Completion Date

August 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

AVIR Green Hills Biotechnology AG

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Seasonal Human Influenza

Keywords

live attenuated flu vaccines, Influenza A (H1N1), intranasally application, replication-deficient influenza virus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cohort I

Arm Type

Other

Arm Description

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

Arm Title

cohort II

Arm Type

Other

Arm Description

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

Arm Title

cohort III

Arm Type

Other

Arm Description

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

Arm Title

cohort IV

Arm Type

Other

Arm Description

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

Arm Title

cohort V

Arm Type

Other

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

GHB01L1

Other Intervention Name(s)

A/New Caledonia/20/99 (H1N1) -like delNS1 virus, GHB01NC(H1N1)

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

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

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Volker Wacheck, MD

Organizational Affiliation

Medical University Vienna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University Vienna, Vienna General Hospital, Dpmt. of Clinical Pharmacology

City

Vienna

ZIP/Postal Code

A-1090

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

24560674

Citation

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.

Results Reference

derived

PubMed Identifier

20039806

Citation

Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T. A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis. 2010 Feb 1;201(3):354-62. doi: 10.1086/649428.

Results Reference

derived

Learn more about this trial

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

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