CompletedNCT02525055Updated Jan 27, 2020Results posted

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

An interventional study of Infectious titre 1 (H3N2) and Infectious titre 2 (H3N2) in Influenza, sponsored by Hvivo. Completed. Open to participants aged 18 Years to 64 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-27.

Sponsored by Hvivo · Not applicable, Interventional, and Basic science

Phase: Not applicable
Study type: Interventional
Enrollment: 46
Allocation: Randomized
Ages: 18 Years to 64 Years
Sex: All

Study 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.

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 studied

Influenza

Browse trials for

Influenza, Human 2,209

Keywords

Flu
Influenza
Human Viral Challenge Model
Wild-Type
H3N2
Universal Influenza Vaccine
Intra-seasonal vaccines
Antiviral

Who can participate

Ages eligible: 18 Years to 64 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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 design

Phase: Not applicable
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 46 participants (actual)

Study arms

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)
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)
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)
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)
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)
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)

Interventions

OtherInfectious titre 1 (H3N2)
Infectious titre 1: 2.8 x 10\*3 TCID50/mL
OtherInfectious titre 2 (H3N2)
Infectious titre 2: 2.5 x 10\*4 TCID50/mL
OtherInfectious titre 3 (H3N2)
Infectious titre 3: 3.6 x 10\*5 TCID50/mL
OtherInfectious titre 4 (H3N2)
Infectious titre 4: 4.7 x 10\*6 TCID50/mL
OtherInfectious titre 5 (H3N2) (Subjects aged 18 to 45 years old)
Infectious titre 5: 3.5 x 10\*5 TCID50/mL
OtherInfectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)
Infectious titre 5: 3.5 x 10\*5 TCID50/mL

What researchers measure

Primary outcomes

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)
Time frame: 8 days

Other outcomes

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

Results

Posted Jan 27, 2020

Participant flow

Participant flow — Overall Study
Milestone	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (18 to 45 Years Old)	Infectious Titre 5 (46 to 64 Years Old)
Started	6	6	6	6	6	16
Completed	6	6	6	6	6	16
Not completed	0	0	0	0	0	0

Outcome measures

PrimaryArea 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)

Time frame:: 8 days
Reported as:: Mean · mins*Eq log10 TCID50/mL

Area Under the Curve of Virus Load
mins*Eq log10 TCID50/mL	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (18 to 45 Years Old)	Infectious Titre 5 (46 to 64 Years Old)
Area Under the Curve of Virus Load	-2081.98 ± 869.61	18,973.90 ± 1048.23	15,944.09 ± 13751.39	12,201.14 ± 8877.43	9563.26 ± 10,536.96	11,710.28 ± 11833.87

Other pre-specifiedIncidence (Number and Percentage [%]) of Viral Challenge Emergent Adverse Events

Time frame:: 8 days

Results for this outcome have not been posted.

Adverse events

Collected over Adverse events are collected throughout the study from screening to last study visit (108 days). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Infectious Titre 1	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
Infectious Titre 2	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Infectious Titre 3	0/6 (0%)	0/6 (0%)	3/6 (50%)
Infectious Titre 4	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Infectious Titre 5 (Aged 18 to 45)	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Infectious Titre 5 (Aged 45 to 64)	0/16 (0%)	0/16 (0%)	10/16 (62.5%)

Most frequent other events

Showing 10 of 24

Most frequent other events
Event	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (Aged 18 to 45)	Infectious Titre 5 (Aged 45 to 64)
Procedural haemorrhageInjury, poisoning and procedural complications	1/6	1/6	3/6	1/6	0/6	2/16
C-reactive protein increasedInvestigations	0/6	0/6	0/6	0/6	0/6	3/16
ToothacheGastrointestinal disorders	0/6	0/6	0/6	1/6	0/6	0/16
Seasonal allergyImmune system disorders	0/6	0/6	0/6	0/6	1/6	0/16
Rash pustularInfections and infestations	0/6	1/6	0/6	0/6	0/6	0/16
Spirometry abnormalInvestigations	0/6	0/6	1/6	0/6	0/6	0/16
ALT increasedInvestigations	0/6	0/6	1/6	0/6	0/6	0/16
HeadacheNervous system disorders	0/6	0/6	0/6	0/6	1/6	2/16
Pain in extremityMusculoskeletal and connective tissue disorders	0/6	0/6	0/6	1/6	0/6	0/16
Oropharyngeal painRespiratory, thoracic and mediastinal disorders	0/6	0/6	0/6	1/6	0/6	0/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (18 to 45 Years Old)	Infectious Titre 5 (46 to 64 Years Old)	Total
<=18 years	0	0	0	0	0	0	0
Between 18 and 65 years	6	6	6	6	6	16	46
>=65 years	0	0	0	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (18 to 45 Years Old)	Infectious Titre 5 (46 to 64 Years Old)	Total
Female	4	1	2	3	2	5	17
Male	2	5	4	3	4	11	29

Region of Enrollment
Region of Enrollment(participants)	Infectious Titre 1	Infectious Titre 2	Infectious Titre 3	Infectious Titre 4	Infectious Titre 5 (18 to 45 Years Old)	Infectious Titre 5 (46 to 64 Years Old)	Total
United Kingdom	6	6	6	6	6	16	46

Study locations

No study locations are listed for this record.

References and documents

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 27280602 ↗
Fullen 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. Erratum In: PLoS One. 2016 Jun 9;11(6):e0157211. doi: 10.1371/journal.pone.0157211. PubMed 26761707 ↗

Registry details

Key details

Study ID: NCT02525055
Lead sponsor: Hvivo
Responsible party: Sponsor
First posted: Aug 17, 2015
Start date: Jan 2014
Primary completion: Aug 11, 2014
Completion: Aug 11, 2014
Results posted: Jan 27, 2020
Last update: Jan 27, 2020

Study contacts

Bryan Muray, MD

principal investigator · Hvivo

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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