Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

Influenza, Avian Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled, Phase I Dose- Escalation Study of Two Doses GHB04L1 in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03745274
• Other study ID #: GHB-CS02
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2008
• Est. completion date: May 27, 2009

Study information

• Verified date: November 2018
• Source: AVIR Green Hills Biotechnology AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates safety, tolerability and immunogenicity of two doses of GHB04L1, a liquid formulation of the replication- deficient influenza A/Vietnam/1203/04(H5N1)-like ∆NS1 virus in healthy adults. Subjects are randomised at a ratio of 2:1 for GHB04L1 (6.8 log10 or 7.5 log10 TCID50/dose/volunteer) or placebo.

Description:

GHB04L1 is intended to provide a novel treatment approach for influenza virus H5N1 infection. Based on preclinical data from ferrets that demonstrated protection against challenge with wild-type virus following treatment with various dose levels of GHB04L1, vaccination with GHB04L1 might protect humans from influenza A (H5N1) virus infection.

Due to the lack of the NS1 protein, the ΔNS1 virus replicates efficiently in interferon-deficient cells but has lost its ability to grow in normal hosts and organisms. Immunisation with ΔNS1 mutant virus can cause only an abortive replication cycle in the nasal mucosa of vaccinated individuals. This allows development of replication-deficient intranasal vaccines with genetic stability of the attenuated phenotype and without virus shedding.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 27, 2009
• Est. primary completion date: May 27, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Male or female healthy volunteers, 18-50 years of age

• Seronegative for H5N1 (with antibody titres <1:10 detected in HAI assay)

• Seronegative for H1N1 (with antibody titres =1:20 detected in HAI assay)

• Written informed consent to participate in this study

Exclusion Criteria:

• Acute febrile illness (>37.0°C)

• Positive influenza immunoassay at baseline

• Signs of acute or chronic upper or lower respiratory tract illnesses (sneezing, cough, tonsillitis, otitis, etc.)

• History of severe atopy

• Influenza vaccination 2006/2007 and/or later

• Known increased tendency of nose bleeding

• Volunteers with clinically relevant abnormal paranasal anatomy

• Volunteers with clinically relevant abnormal laboratory values Females with positive urine pregnancy test prior to vaccination

• 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 had undergone rhino or sinus surgery or surgery of another traumatic injury of the nose within 30 days prior to application of study medication

• Volunteers who had received antiviral drugs, treatment with immunoglobulins or blood transfusions or an investigational drug within four weeks prior to study medication application

• Volunteers who had received anti-inflammatory drugs 2 days prior to study medication application

• Volunteers who were 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

Related Conditions & MeSH terms

• Influenza, Avian
• Influenza, Human

Intervention

Biological:
• GHB04L1
Solution

Other:
• Placebo
Buffer solution

Locations

Country	Name	City	State
Russian Federation	Research Institute of Influenza, Russian Academy of Medical Sciences	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
AVIR Green Hills Biotechnology AG

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of adverse events	Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration	8 weeks
Secondary	Viral shedding	Presence of GHB04L1 in mucosal samples from the nose	3 days
Secondary	Local immune response	Local influenza A virus-specific immune response (IgA) in mucosal samples from the nose	8 weeks
Secondary	Local cytokines response	Local cytokines response in mucosal samples from the nose	3 days
Secondary	Systemic influenza A virus-specific antibody response	Systemic influenza A virus-specific antibody response determined by haemagglutination-inhibition assay (HAI) and micro-neutralisation assay (MNA) in serum samples	8 weeks
Secondary	Systemic influenza A virus-specific T-cell response	Systemic influenza A virus-specific T-cell response determined by T-cell proliferation assay in blood samples	8 weeks
Secondary	Systemic natural killer cell cytotoxicity	Systemic natural killer cell cytotoxicity in blood samples	5 weeks
Secondary	Systemic T-cell Granzyme B assay	Systemic T-cell Granzyme B assay in blood samples	8 weeks