Influenza, AvianPhase 1NCT03745274
Two Doses of GHB04L1 for Pandemic Influenza Prophylaxis in Healthy Adults
A Phase 1 study testing GHB04L1 in people with Influenza, Avian, run by AVIR Green Hills Biotechnology AG at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Avian
- What is being tested?
- GHB04L1
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteRussia
- Study dates
- 19 Dec 2008to 27 May 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Russia1 site
Research Institute of Influenza, Russian Academy of Medical Sciences
Saint Petersburg, 197376
About this study
Official title: 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.
Read the 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.
- Conditions
- Influenza, Avian
- Being tested
- GHB04L1, Placebo
- Medical subject headings
- Influenza in Birds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GHB04L1Biological
Solution
PlaceboOther
Buffer solution
| Study group | Role | What they receive |
|---|---|---|
| GHB04L1 | Experimental | 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. Receives: Biological: GHB04L1 |
| Placebo | Placebo comparator | Placebo (buffer) is administered as intranasal aerosol on day 1 and on day 29. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of adverse events
Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration
Measured: 8 weeks
Secondary outcomes (7)
Viral shedding
Presence of GHB04L1 in mucosal samples from the nose
Measured: 3 days
Local immune response
Local influenza A virus-specific immune response (IgA) in mucosal samples from the nose
Measured: 8 weeks
Local cytokines response
Local cytokines response in mucosal samples from the nose
Measured: 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
Measured: 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
Measured: 8 weeks
Systemic natural killer cell cytotoxicity
Systemic natural killer cell cytotoxicity in blood samples
Measured: 5 weeks
Systemic T-cell Granzyme B assay
Systemic T-cell Granzyme B assay in blood samples
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start19 Dec 2008
- Primary completion27 May 2009
- Study completion27 May 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Influenza, AvianStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVIR Green Hills Biotechnology AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oleg Kiselev, Prof, Principal investigator, Research Institute of Influenza, Russian Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03745274
- Sponsor's protocol ID
- GHB-CS02
- Status last verified
- Nov 2018
- First submitted
- 15 Nov 2018
- Last updated
- 20 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31155415
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-blind, Placebo-controlled, Phase I Dose- Escalation Study of Two Doses GHB04L1 in Healthy Adults
- ClinicalTrials.gov ID
- NCT03745274
- Acronym / sponsor ID
- GHB-CS02
- Conditions
- Influenza, Avian
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AVIR Green Hills Biotechnology AGIndustry (pharma, biotech, devices)
- Study start
- 19 Dec 2008 (actual)
- Primary completion
- 27 May 2009 (actual)
- Study completion
- 27 May 2009 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GHB04L1 | Experimental | Biological: GHB04L1GHB04L1 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 | Placebo comparator | Other: PlaceboPlacebo (buffer) is administered as intranasal aerosol on day 1 and on day 29. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GHB04L1Solution | Biological | GHB04L1 |
| PlaceboBuffer solution | Other | Placebo |
Primary outcome
Occurrence of adverse events
Time frame: 8 weeks
Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration
7 secondary outcomes
Viral shedding
Time frame: 3 days
Local immune response
Time frame: 8 weeks
Local cytokines response
Time frame: 3 days
Systemic influenza A virus-specific antibody response
Time frame: 8 weeks
Systemic influenza A virus-specific T-cell response
Time frame: 8 weeks
Systemic natural killer cell cytotoxicity
Time frame: 5 weeks
Systemic T-cell Granzyme B assay
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Derived from this study: PubMed 31155415Nicolodi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oleg Kiselev, Prof principal investigator
Research Institute of Influenza, Russian Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GHB04L1 in people with Influenza, Avian, run by AVIR Green Hills Biotechnology AG at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of adverse events (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03745274, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2018.