Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza, Avian
• Intervention / Treatment: Biological: GHB04L1; Other: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197376
    • Research Institute of Influenza, Russian Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GHB04L1; GHB04L1 is administered as intranasal aerosol at a dose of 6.8 log10 or 7.5 log10 TCID50/dose/subject on day 1 and on day 29.	Biological: GHB04L1; Solution
Placebo Comparator: Placebo; Placebo (buffer) is administered as intranasal aerosol on day 1 and on day 29.	Other: Placebo; Buffer solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral shedding	Presence of GHB04L1 in mucosal samples from the nose	3 days
Local immune response	Local influenza A virus-specific immune response (IgA) in mucosal samples from the nose	8 weeks
Local cytokines response	Local cytokines response in mucosal samples from the nose	3 days
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
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
Systemic natural killer cell cytotoxicity	Systemic natural killer cell cytotoxicity in blood samples	5 weeks
Systemic T-cell Granzyme B assay	Systemic T-cell Granzyme B assay in blood samples	8 weeks

Collaborators and Investigators

• Sponsor: AVIR Green Hills Biotechnology AG
• Investigators: Principal Investigator: Oleg Kiselev, Prof, Research Institute of Influenza, Russian Academy of Medical Sciences

Publications and helpful links

General Publications

• Nicolodi C, Groiss F, Kiselev O, Wolschek M, Seipelt J, Muster T. Safety and immunogenicity of a replication-deficient H5N1 influenza virus vaccine lacking NS1. Vaccine. 2019 Jun 19;37(28):3722-3729. doi: 10.1016/j.vaccine.2019.05.013. Epub 2019 May 30.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2008
• Primary Completion (Actual): May 27, 2009
• Study Completion (Actual): May 27, 2009

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 18, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: GHB-CS02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No