Characterisation of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model

January 23, 2020 updated by: Hvivo

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Infectious titre 1
6 participants aged 18 to 45 were inoculated with 1mL containing 2.8 x 10*3 TCID50 of virus
Other: Infectious titre 1 (H3N2)
Infectious titre 1: 2.8 x 10*3 TCID50/mL
Experimental: Infectious titre 2
6 participants aged 18 to 45 were inoculated with 1mL containing 2.5 x 10*4 TCID50 of virus
Other: Infectious titre 2 (H3N2)
Infectious titre 2: 2.5 x 10*4 TCID50/mL
Experimental: Infectious titre 3
6 participants aged 18 to 45 were inoculated with 1mL containing 3.6 x 10*5 TCID50 of virus
Other: Infectious titre 3 (H3N2)
Infectious titre 3: 3.6 x 10*5 TCID50/mL
Experimental: Infectious titre 4
6 participants aged 18 to 45 were inoculated with 1mL containing 4.7 x 10*6 TCID50 of virus
Other: Infectious titre 4 (H3N2)
Infectious titre 4: 4.7 x 10*6 TCID50/mL
Experimental: Infectious titre 5 (age 18 to 45 y)
6 participants aged 18 to 45 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus.
Other: Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)
Infectious titre 5: 3.5 x 10*5 TCID50/mL
Experimental: Infectious titre 5 (age 46 to 64 y)
16 participants aged 46 to 64 were inoculated with 1mL containing 3.5 x 10*5 TCID50 of virus.
Other: Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)
Infectious titre 5: 3.5 x 10*5 TCID50/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
8 days

Other Outcome Measures

Outcome Measure
Time Frame
Incidence (Number and Percentage [%]) of Viral Challenge Emergent Adverse Events
Time Frame: 8 days
8 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hvivo

Investigators

  • Principal Investigator: Bryan Muray, MD, Hvivo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

August 11, 2014

Study Completion (Actual)

August 11, 2014

Study Registration Dates

First Submitted

August 6, 2015

First Submitted That Met QC Criteria

August 13, 2015

First Posted (Estimate)

August 17, 2015

Study Record Updates

Last Update Posted (Actual)

January 27, 2020

Last Update Submitted That Met QC Criteria

January 23, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RVL-vCS-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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