InfluenzaNCT02525055
Characterisation of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model
A study testing Infectious titre 1 (H3N2), Infectious titre 2 (H3N2) and Infectious titre 3 (H3N2) in people with Influenza, run by Hvivo.
Trial summary
The study will characterise Influenza A/Perth/16/2009(H3N2) virus in healthy participants using the viral challenge model. The study includes two cohorts. Cohort 1: A randomised, double-blind study of 4 titres of Challenge Virus to determine the optimum titre. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Infectious titre 1 (H3N2), Infectious titre 2 (H3N2) and Infectious titre 3 (H3N2)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to 11 Aug 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In good health with no history of major medical conditions.
- A total body weight ≥ 50 kg and a BMI of >18.
- Acceptable forms of effective contraception.
- An informed consent document signed and dated by the subject and Investigator.
- Sero-suitable for Challenge Virus.
Who cannot join
- Subjects who have a significant history of any tobacco use at any time (≥ total 10 pack year history, e.g. one pack a day for 10 years).
- Subjects who have been pregnant within six months prior to the study, or who have a positive pregnancy test at any point in the study.
- Any history or evidence of any clinically significant medical conditions (cardiovascular, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychotic, renal, and/or other major disease or malignancy).
- History or evidence of autoimmune disease or known immunodeficiency of any cause.
- Subjects with any history of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung condition of any aetiology.
- Positive human immunodeficiency virus (HIV), Hepatitis A (HAV), B (HBV), or C (HCV) test.
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- Any significant abnormality altering the anatomy of the nose or nasopharynx.
- Any clinically significant history of epistaxis (nose bleeds).
- Any nasal or sinus surgery within six months of inoculation.
- Recurrent history of clinically significant autonomic dysfunction.
- Any abnormal laboratory test or ECG.
- Confirmed positive test for drugs of abuse.
- Venous access deemed inadequate for the phlebotomy and cannulation.
- Any known allergies to the excipients in the Challenge Virus inoculums.
- Health care workers who work in units with severely immuno-compromised patients.
- Evidence of vaccinations within the four weeks prior to Human Viral Challenge or intention to receive travel vaccination before the last study visit.
- Receipt of blood or blood products, or loss (including blood donations) of 450 mL or more of blood, during the 3 months prior to inoculations.
- Presence of significant respiratory symptoms existing on the day of challenge or between admission to the unit and inoculation with virus.
- History suggestive of respiratory infection within 14 days prior to admission to the unit.
- Use within 28 days prior to Human Viral Challenge (Day 0) of nasal steroids * Use within seven days of any other medication or product (prescription or over-the-counter), for symptoms of hay fever, rhinitis, nasal congestion or respiratory tract infection.
- Receipt of systemic: glucocorticoids, antiviral drugs, or immunoglobulins (Igs) or any other cytotoxic or immunosuppressive drug.
- Receipt of any systemic chemotherapy agent at any time.
About this study
Official title: A Randomised, Double Blind Study To Characterise Influenza A/Perth/16/2009(H3N2) Virus
The study will characterise Influenza A/Perth/16/2009(H3N2) virus in healthy participants using the viral challenge model. The study includes two cohorts.
Cohort 1: A randomised, double-blind study of 4 titres of Challenge Virus to determine the optimum titre.
Cohort 2: An open-label extension arm in which all participants will receive the 'optimum' titre as identified from Cohort 1.
Read the detailed description
Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. Studies using experimental influenza virus infection in human participants have demonstrated that adult volunteers can be infected by nasal inoculation, and experimental infection is safe and not associated with transmission to contacts. The experimental virus is manufactured in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model.
The investigators chose an H3N2 influenza subtype given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control . The investigators first subjected the virus batch to rigorous adventitious agent testing, then confirmed the virus to be wild-type by Sanger sequencing and finally determined the virus titres appropriate for human use via the established ferret model. hVIVO team built on its previous experience with other H3N2 and H1N1 viruses to develop this unique model.
The first part of study (Cohort 1) was to determine the safety and optimal virus titre in healthy adult volunteers using our unique clinical quarantine facility in London, UK. After the first part of the study was completed, the study was amended to add an older population group (45-64 years old) in order to characterise the course of infection in an age group better representing the at-risk population.
- Conditions
- Influenza
- Being tested
- Infectious titre 1 (H3N2), Infectious titre 2 (H3N2), Infectious titre 3 (H3N2), Infectious titre 4 (H3N2), Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)
- Keywords
- Flu, Influenza, Human Viral Challenge Model, Wild-Type, H3N2, Universal Influenza Vaccine, Intra-seasonal vaccines, Antiviral
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infectious titre 1 (H3N2)Other
Infectious titre 1: 2.8 x 10*3 TCID50/mL
Infectious titre 2 (H3N2)Other
Infectious titre 2: 2.5 x 10*4 TCID50/mL
Infectious titre 3 (H3N2)Other
Infectious titre 3: 3.6 x 10*5 TCID50/mL
Infectious titre 4 (H3N2)Other
Infectious titre 4: 4.7 x 10*6 TCID50/mL
Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)Other
Infectious titre 5: 3.5 x 10*5 TCID50/mL
Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)Other
Infectious titre 5: 3.5 x 10*5 TCID50/mL
| Study group | Role | What they receive |
|---|---|---|
| Infectious titre 1 | Experimental | 6 participants aged 18 to 45 were inoculated with 1mL containing 2.8 x 10*3 TCID50 of virus Receives: Other: Infectious titre 1 (H3N2) |
| Infectious titre 2 | Experimental | 6 participants aged 18 to 45 were inoculated with 1mL containing 2.5 x 10*4 TCID50 of virus Receives: Other: Infectious titre 2 (H3N2) |
| Infectious titre 3 | Experimental | 6 participants aged 18 to 45 were inoculated with 1mL containing 3.6 x 10*5 TCID50 of virus Receives: Other: Infectious titre 3 (H3N2) |
| Infectious titre 4 | Experimental | 6 participants aged 18 to 45 were inoculated with 1mL containing 4.7 x 10*6 TCID50 of virus Receives: Other: Infectious titre 4 (H3N2) |
| Infectious titre 5 (age 18 to 45 y) | Experimental | 6 participants aged 18 to 45 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus. Receives: Other: Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old) |
| Infectious titre 5 (age 46 to 64 y) | Experimental | 16 participants aged 46 to 64 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus. Receives: Other: Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve of Virus Load
Area under the curve (AUC) of the Challenge Viral load, measured by nasopharyngeal swab quantitative polymerase chain reaction [qPCR], from Day 1 to Day 8 post-Viral Challenge. Nasopharyngeal swabs are collected up to 3 times per day ( every 8 hours +/- 30mins)
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study startJan 2014
- Primary completion11 Aug 2014
- Study completion11 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hvivo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bryan Muray, MD, Principal investigator, Hvivo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525055
- Sponsor's protocol ID
- RVL-vCS-003
- Status last verified
- Jan 2020
- First submitted
- 6 Aug 2015
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Fullen DJ, Noulin N, Catchpole A, Fathi H, Murray EJ, Mann A, Eze K, Balaratnam G, Borley DW, Gilbert A, Lambkin-Williams R. Correction: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model. PLoS One. 2016 Jun 9;11(6):e0157211. doi: 10.1371/journal.pone.0157211. eCollection 2016.
PubMed 27280602Fullen DJ, Noulin N, Catchpole A, Fathi H, Murray EJ, Mann A, Eze K, Balaratnam G, Borley DW, Gilbert A, Lambkin-Williams R. Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model. PLoS One. 2016 Jan 13;11(1):e0145902. doi: 10.1371/journal.pone.0145902. eCollection 2016.
PubMed 26761707
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double Blind Study To Characterise Influenza A/Perth/16/2009(H3N2) Virus
- ClinicalTrials.gov ID
- NCT02525055
- Acronym / sponsor ID
- RVL-vCS-003
- Conditions
- Influenza
- Keywords
- Flu, Influenza, Human Viral Challenge Model, Wild-Type, H3N2, Universal Influenza Vaccine, Intra-seasonal vaccines, Antiviral
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- HvivoIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- 11 Aug 2014 (actual)
- Study completion
- 11 Aug 2014 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will characterise Influenza A/Perth/16/2009(H3N2) virus in healthy participants using the viral challenge model. The study includes two cohorts.
Cohort 1: A randomised, double-blind study of 4 titres of Challenge Virus to determine the optimum titre.
Cohort 2: An open-label extension arm in which all participants will receive the 'optimum' titre as identified from Cohort 1.
Detailed description
Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. Studies using experimental influenza virus infection in human participants have demonstrated that adult volunteers can be infected by nasal inoculation, and experimental infection is safe and not associated with transmission to contacts. The experimental virus is manufactured in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model.
The investigators chose an H3N2 influenza subtype given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control . The investigators first subjected the virus batch to rigorous adventitious agent testing, then confirmed the virus to be wild-type by Sanger sequencing and finally determined the virus titres appropriate for human use via the established ferret model. hVIVO team built on its previous experience with other H3N2 and H1N1 viruses to develop this unique model.
The first part of study (Cohort 1) was to determine the safety and optimal virus titre in healthy adult volunteers using our unique clinical quarantine facility in London, UK. After the first part of the study was completed, the study was amended to add an older population group (45-64 years old) in order to characterise the course of infection in an age group better representing the at-risk population.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Infectious titre 1 | Experimental | Other: Infectious titre 1 (H3N2)6 participants aged 18 to 45 were inoculated with 1mL containing 2.8 x 10*3 TCID50 of virus |
| Infectious titre 2 | Experimental | Other: Infectious titre 2 (H3N2)6 participants aged 18 to 45 were inoculated with 1mL containing 2.5 x 10*4 TCID50 of virus |
| Infectious titre 3 | Experimental | Other: Infectious titre 3 (H3N2)6 participants aged 18 to 45 were inoculated with 1mL containing 3.6 x 10*5 TCID50 of virus |
| Infectious titre 4 | Experimental | Other: Infectious titre 4 (H3N2)6 participants aged 18 to 45 were inoculated with 1mL containing 4.7 x 10*6 TCID50 of virus |
| Infectious titre 5 (age 18 to 45 y) | Experimental | Other: Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)6 participants aged 18 to 45 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus. |
| Infectious titre 5 (age 46 to 64 y) | Experimental | Other: Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)16 participants aged 46 to 64 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- In good health with no history of major medical conditions.
- A total body weight ≥ 50 kg and a BMI of >18.
- Acceptable forms of effective contraception.
- An informed consent document signed and dated by the subject and Investigator.
- Sero-suitable for Challenge Virus.
Key exclusion criteria (22 listed)
- Subjects who have a significant history of any tobacco use at any time (≥ total 10 pack year history, e.g. one pack a day for 10 years).
- Subjects who have been pregnant within six months prior to the study, or who have a positive pregnancy test at any point in the study.
- Any history or evidence of any clinically significant medical conditions (cardiovascular, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychotic, renal, and/or other major disease or malignancy).
- History or evidence of autoimmune disease or known immunodeficiency of any cause.
- Subjects with any history of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung condition of any aetiology.
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 |
|---|---|---|
| Infectious titre 1 (H3N2)Infectious titre 1: 2.8 x 10*3 TCID50/mL | Other | Infectious titre 1 |
| Infectious titre 2 (H3N2)Infectious titre 2: 2.5 x 10*4 TCID50/mL | Other | Infectious titre 2 |
| Infectious titre 3 (H3N2)Infectious titre 3: 3.6 x 10*5 TCID50/mL | Other | Infectious titre 3 |
| Infectious titre 4 (H3N2)Infectious titre 4: 4.7 x 10*6 TCID50/mL | Other | Infectious titre 4 |
| Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)Infectious titre 5: 3.5 x 10*5 TCID50/mL | Other | Infectious titre 5 (age 18 to 45 y) |
| Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)Infectious titre 5: 3.5 x 10*5 TCID50/mL | Other | Infectious titre 5 (age 46 to 64 y) |
Primary outcome
Area Under the Curve of Virus Load
Time frame: 8 days
Area under the curve (AUC) of the Challenge Viral load, measured by nasopharyngeal swab quantitative polymerase chain reaction [qPCR], from Day 1 to Day 8 post-Viral Challenge. Nasopharyngeal swabs are collected up to 3 times per day ( every 8 hours +/- 30mins)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27280602Fullen DJ, Noulin N, Catchpole A, Fathi H, Murray EJ, Mann A, Eze K, Balaratnam G, Borley DW, Gilbert A, Lambkin-Williams R. Correction: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model. PLoS One. 2016 Jun 9;11(6):e0157211. doi: 10.1371/journal.pone.0157211. eCollection 2016.
- Derived from this study: PubMed 26761707Fullen DJ, Noulin N, Catchpole A, Fathi H, Murray EJ, Mann A, Eze K, Balaratnam G, Borley DW, Gilbert A, Lambkin-Williams R. Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model. PLoS One. 2016 Jan 13;11(1):e0145902. doi: 10.1371/journal.pone.0145902. eCollection 2016.
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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.
Bryan Muray, MD principal investigator
Hvivo
Questions about this trial
What is this clinical trial studying?
A study testing Infectious titre 1 (H3N2), Infectious titre 2 (H3N2) and Infectious titre 3 (H3N2) in people with Influenza, run by Hvivo.
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 5 inclusion and 22 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 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Curve of Virus Load (time frame: 8 days). 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 NCT02525055, which also lists 2 linked publications.
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 27 Jan 2020.