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

NCT ID: NCT00724997

Last Updated: 2009-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2008-08-31

Brief Summary

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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

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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.

Conditions

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Seasonal Human Influenza

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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cohort I

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

Group Type OTHER

GHB01L1

Intervention Type BIOLOGICAL

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

cohort II

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

Group Type OTHER

GHB01L1

Intervention Type BIOLOGICAL

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

cohort III

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

Group Type OTHER

GHB01L1

Intervention Type BIOLOGICAL

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

cohort IV

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

Group Type OTHER

GHB01L1

Intervention Type BIOLOGICAL

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

cohort V

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

Group Type OTHER

GHB01L1

Intervention Type BIOLOGICAL

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

Interventions

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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

Intervention Type BIOLOGICAL

Other Intervention Names

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

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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AVIR Green Hills Biotechnology AG

INDUSTRY

Sponsor Role lead

Responsible Party

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AVIR Green Hills Biotechnology AG

Principal Investigators

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Volker Wacheck, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna

Locations

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

Vienna, , Austria

Site Status

Countries

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Austria

References

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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.

Reference Type DERIVED
PMID: 24560674 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20039806 (View on PubMed)

Other Identifiers

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EudraCT 2006-001176-20

Identifier Type: -

Identifier Source: secondary_id

GHB-CS01

Identifier Type: -

Identifier Source: org_study_id