Single Dose Texas 2017 (H3N2) Challenge Study

NCT06476275 | Completed Phase 1 FDA Drug

• 1 other identifier: Pro00114712
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of the present study is to utilize the recombinant H3N2 (A/Texas/71/2017 (H3N2, clade 3C3a)) influenza virus for a controlled human infection model to study host responses to influenza virus with the aim of identifying volatile markers in exhaled breath and expression markers in saliva for early detection of infection after pathogen exposure. This study will aim to recruit up to 40 healthy volunteers between ages 18-45 who will receive a single dose of either intranasally administered placebo (sham inoculum) or the virus challenge strain at a concentration known to elicit a \~60-80% attack rate. The response to influenza challenge will be measured by clinical, laboratory, immunological, digital biomarker, on-breath volatile organic compound data and host RNA expression in both blood and saliva. The study will enroll and challenge up to 34 healthy adult volunteers with live virus plus approximately 6 sham-inoculated controls who will be prescreened for study inclusion to have serological antibody titers of ≤1:40 against the challenge strain. Each participant will complete up to 3 weeks of follow-up post confinement.

Conditions

Influenza Viral Infections

Keywords

Host response; Wearable monitoring devices; Influenza challenge study

Outcome Measures

Primary Outcomes (3)

• Number of participants with detectable viral shedding in nasopharyngeal (NP) swab(s) by qualitative RT-PCR over any 2 days and with symptomatic infection

  24 hours post challenge through Day 8

• Number of participants with On-breath volatile markers that correlate with clinical symptoms

  On-breath volatile markers that correlate with early, pre-symptomatic influenza viral infection, early asymptomatic influenza viral infection, clinical symptoms of infection throughout the confinement period and viral shedding. Captured by the Owlstone Medical Breath Biopsy Collection Station and identified and quantified by thermal-desorption gas chromatography mass spectrometry (TD-GC-MS).

  Baseline (Day -1) through Day 8

• Number of participants with Biomarker expression changes that correlate with clinical symptoms

  Biomarker expression changes in saliva that correlate with early, pre-symptomatic influenza viral infection, early asymptomatic influenza viral infection, clinical symptoms of infection throughout the confinement period and viral shedding. Quantitative RNA expression levels at baseline and post challenge serial timepoints using next-level genomic sequencing (NGS) and RT-qPCR.

  Baseline (Day -1) through Day 8

Study Arms (2)

Influenza A/Texas/71/2017 (H3N2)

EXPERIMENTAL

Recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus at 106 TCID50 dose. This dose has an attack rate of \>70%, and a good safety profile related to adverse events reporting. Each vial of virus stock and diluent will be individually labeled with the product name, description and caution statement.

Biological: Influenza A/Texas/71/2017 (H3N2)

Sham Product

SHAM COMPARATOR

The viral stock diluent will be used as a sham inoculum, without the viral stock added. Each vial of sham will be labeled with the product name, description and caution statement.

Biological: Sham placebo

Interventions

Influenza A/Texas/71/2017 (H3N2) BIOLOGICAL

Virus will be administered intranasally

Influenza A/Texas/71/2017 (H3N2)

Sham placebo BIOLOGICAL

Placebo will be administered intranasally

Sham Product

Eligibility Criteria

• Age: 18 Years - 46 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedure
• Are able to understand and comply with planned study procedures and be available for all study visits
• Agree to remain an inpatient for at least 7 days after challenge AND until they have no viral shedding, determined by qualitative RT-PCR beginning on Study Day 6
• Healthy males and non-pregnant, non-breastfeeding females aged ≥ 18 and \< 46 years of age at enrollment NOTE: Female subjects of childbearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test upon admission to the confinement unit AND a negative pregnancy test before any CXR (if ≥ 7 days have passed since a serum pregnancy test).
• Women of childbearing potential must agree to use or have practiced true abstinence or use at least one acceptable primary form of contraception for at least 30 days prior to challenge
• Non-habitual smoker of tobacco, e-cigarettes or marijuana
• No self-reported or known history of alcoholism within the last 2 years and agrees to abstain from alcohol for at least one week before admission and throughout the confinement period
• No self-reported or known history of restricted drug use for at least 30 days prior to challenge and agrees to abstain from restricted drugs throughout the confinement period
• Negative drug urine toxicology result on screening (i.e., amphetamines, cocaine, and opiates) and on admission to the challenge unit (i.e., amphetamines, cocaine, and opiates)
• Agree not to use the listed prescription or over the counter medications within 7 days prior to and through confinement period, unless approved by the investigator

You may not qualify if:

• Vital signs as follows:
• Pulse is 47 to 99 beats per minute, inclusive
• Systolic blood pressure is 85 to 139 mmHg, inclusive
• Diastolic blood pressure is 55 to 89 mmHg, inclusive
• SpO2 \> 95%; RR \< 18
• Oral temperature is less than 100.6°F
• Eligibility laboratory values (WBC, Absolute Lymphocyte Count, Hgb, PLTs, ALT and Cr) are within acceptable parameters
• Body mass index (BMI) \>18.5 and \<40 kg/m2 at screening
• Other screening tests (ECG and CXR) are within normal reference range or not deemed clinically significant by the PI or appropriate sub-investigator
• Negative test for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) at screening
• Negative multiplex respiratory virus panel on Day -2, and Day -1
• Negative RT-PCR test for SARS-CoV-2 on screening and Day -2
• HAI antibody titer ≤1:40 against influenza A/Texas/71/2017 (H3N2) at screening
• Presence of self-reported or medically documented significant medical or psychiatric condition(s)
• NOTE: Significant medical or psychiatric conditions include but are not limited to:

Sponsors & Collaborators

• Duke University: lead
• United States Department of Defense: collaborator
• Owlstone Ltd: collaborator
• Darwin Biosciences: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2024
• First Posted: June 26, 2024
• Study Start: September 11, 2024
• Primary Completion: January 15, 2025
• Study Completion: February 10, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)