Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

AVIR Green Hills Biotechnology

Status and phase

Completed

Phase 1

Conditions

Influenza, Avian

Treatments

Biological: GHB04L1

Other: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT03745274

GHB-CS02

Details and patient eligibility

About

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.

Full 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.

Enrollment

36 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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