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Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

Primary Purpose

Influenza, Avian

Status

Completed

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

GHB04L1

Placebo

About this trial

This is an interventional prevention trial for Influenza, Avian

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts 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

Sites / Locations

Research Institute of Influenza, Russian Academy of Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GHB04L1

Placebo

Arm Description

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.

Placebo (buffer) is administered as intranasal aerosol on day 1 and on day 29.

Outcomes

Primary Outcome Measures

Occurrence of adverse events

Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration

Secondary Outcome Measures

Viral shedding

Presence of GHB04L1 in mucosal samples from the nose

Local immune response

Local influenza A virus-specific immune response (IgA) in mucosal samples from the nose

Local cytokines response

Local cytokines response in mucosal samples from the nose

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

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

Systemic natural killer cell cytotoxicity

Systemic natural killer cell cytotoxicity in blood samples

Systemic T-cell Granzyme B assay

Systemic T-cell Granzyme B assay in blood samples

Full Information

NCT ID

NCT03745274

First Posted

November 15, 2018

Last Updated

November 18, 2018

Sponsor

AVIR Green Hills Biotechnology AG

1. Study Identification

Unique Protocol Identification Number

NCT03745274

Brief Title

Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Completed

Study Start Date

December 19, 2008 (Actual)

Primary Completion Date

May 27, 2009 (Actual)

Study Completion Date

May 27, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AVIR Green Hills Biotechnology AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

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

Influenza, Avian

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GHB04L1

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo (buffer) is administered as intranasal aerosol on day 1 and on day 29.

Intervention Type

Biological

Intervention Name(s)

GHB04L1

Intervention Description

Solution

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Buffer solution

Primary Outcome Measure Information:

Title

Occurrence of adverse events

Description

Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Viral shedding

Description

Presence of GHB04L1 in mucosal samples from the nose

Time Frame

3 days

Title

Local immune response

Description

Local influenza A virus-specific immune response (IgA) in mucosal samples from the nose

Time Frame

8 weeks

Title

Local cytokines response

Description

Local cytokines response in mucosal samples from the nose

Time Frame

3 days

Title

Systemic influenza A virus-specific antibody response

Description

Systemic influenza A virus-specific antibody response determined by haemagglutination-inhibition assay (HAI) and micro-neutralisation assay (MNA) in serum samples

Time Frame

8 weeks

Title

Systemic influenza A virus-specific T-cell response

Description

Systemic influenza A virus-specific T-cell response determined by T-cell proliferation assay in blood samples

Time Frame

8 weeks

Title

Systemic natural killer cell cytotoxicity

Description

Systemic natural killer cell cytotoxicity in blood samples

Time Frame

5 weeks

Title

Systemic T-cell Granzyme B assay

Description

Systemic T-cell Granzyme B assay in blood samples

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Oleg Kiselev, Prof

Organizational Affiliation

Research Institute of Influenza, Russian Academy of Medical Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Institute of Influenza, Russian Academy of Medical Sciences

City

Saint Petersburg

ZIP/Postal Code

197376

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31155415

Citation

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.

Results Reference

derived

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Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults

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