Influenza Challenge Study to Determine the Optimal Infection Dose and Safety of a Recombinant H3N2 (A/Texas/71/2017 (H3N2, Clade 3C3a) Influenza Strain

NCT04978454 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20-000575N93019C00054
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

An open-label, dose-ranging influenza challenge study in healthy adult volunteers to determine the optimal infection dose and safety of a recombinant H3N2 (A/Texas/ A/Texas/71/2017 (H3N2, clade 3C3a) influenza strain. The goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be sufficiently high for utilization in future vaccine or intervention studies. The optimal dose of the three considered is broadly defined as the minimum challenge virus dose that elicits the highest AR without meeting safety-stopping criteria. Additionally, viral recovery, clinical symptoms, and immune responses over the post-challenge period will be described by challenge dose group. This study will last for up to 1 year depending upon the number of challenge cohorts enrolled given the adaptive dose-escalation design. The populations are healthy males and non-pregnant, non-breastfeeding females aged = 18 and \< 46 years of age with a serum HAI antibody titer of \</=1:40 against influenza A/Texas/71/2017 (H3N2), clade 3C3a. The study will enroll and challenge up to 106 (plus 8 shams) healthy adult volunteers with the H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus challenge strain. The primary objectives are: 1) To determine the optimal infectious dose of a recombinant influenza virus (A/Texas/71/2017 (H3N2), clade 3C3a) to be used as a clinical challenge strain in future vaccine efficacy or intervention studies as assessed by viral shedding and clinical symptoms. 2) To describe viral detection by quantitative and qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) from study subjects at baseline and post-challenge. 3) To document clinical symptoms from self-reported surveys and standardized symptom scales at baseline and post-challenge.

Conditions

Influenza

Keywords

A/Texas/71/2017; Influenza; Influenza Challenge Study; Recombinant H3N2; Recombinant H3N2 Influenza Strain; Safety

Outcome Measures

Primary Outcomes (6)

• Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge.

  Symptomatic influenza virus infection is defined as meeting both of the following criteria: 1. Viral shedding (as determined by a positive qualitative RT-PCR result or a detectable quantitative RT-PCR result) on at least two days beginning 24 hours after challenge until Study Day 8. 2. A cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes.

  Day 2 through Day 8

• Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge.

  Viral shedding status (yes/no) is determined by at least one of: a positive qualitative reverse transcription-polymerase chain reaction (RT-PCR) result from multiplex assay, or a detectable quantitative RT-PCR result.

  Day 1 through discharge from the inpatient unit (Day 8 to Day 10)

• Mean Peak Viral Load (VL) After Challenge

  The magnitude of viral shedding is measured via quantitative RT-PCR. Peak VL post-challenge is computed for each participant as the maximum log-10 viral copies/mL.

  Day 2 through Day 8

• Mean Duration of Viral Shedding

  Viral shedding status (yes/no) for each day during the challenge period is determined by at least one of: a positive qualitative RT-PCR result from multiplex assay, or a detectable quantitative RT-PCR result. The duration of shedding for each participant was computed as the number of days from the initial positive NP swab until the day after the final positive NP swab. Intermittent negative results were ignored for this computation.

  Day 2 through Day 8

• Mean Maximum Cumulative Modified Jackson Score (MJS)

  The cumulative symptom score from daily component symptoms is computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using the Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. The maximum cumulative score post-challenge was computed for each participant.

  Day 2 through Day 8

• Number and Percentage of Participants Symptomatic for Influenza.

  Participants were categorized as symptomatic if they reported a cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes.

  Day 2 through Day 8

Secondary Outcomes (10)

• Number of Adverse Events (AEs) Reported From Challenge Through Day 29

  Day 1 through Day 29

• Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29.

  Day 1 through Day 29

• Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57

  Day 1 through Day 57

• Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57

  Day 1 through Day 57

• Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day

  Day 8, Day 15, and Day 29

Study Arms (8)

Cohort 1A

EXPERIMENTAL

10\^4 TCID50of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 80% of subjects meet the case definition for influenza in Cohort 1A, the dose will escalate to include Cohort 2A. N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 1B

EXPERIMENTAL

10\^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A and 1B meet the case definition for influenza, proceed to Cohort 1C. Cumulatively, if fewer than 80% of subjects in Cohorts 1A and 1B meet the case definition for influenza, the dose will escalate to include Cohort 2A. N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 1C

EXPERIMENTAL

10\^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and sham sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more of the subjects in Cohorts 1A, 1B, and 1C combined meet the case definition for influenza then the optimal dose of 104 TCID50 will be selected. Cumulatively, if fewer than 80% of subjects in Cohorts 1A, 1B, and 1C meet the case definition for influenza the dose will escalate to include Cohort 2A. N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 2A

EXPERIMENTAL

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more subjects in Cohort 2A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 70% of subjects meet the case definition for influenza in Cohort 2A, the dose will escalate to include Cohort 3A. N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 2B

EXPERIMENTAL

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1.If 70% or more subjects in Cohort 2A and 2B meet the case definition for influenza, proceed to Cohort 2C. Cumulatively, if fewer than 70% of subjects in Cohorts 2A and 2B meet the case definition for influenza, the dose will escalate to include Cohort 3A N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 2C

EXPERIMENTAL

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more of the subjects in Cohorts 2A, 2B, and 2C combined meet the case definition for influenza then the optimal dose of 10\^4 TCID50 will be selected. Cumulatively, if fewer than 70% of subjects in Cohorts 2A, 2B, and 2C meet the case definition for influenza the dose will escalate to include Cohort 3A. N = 13

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 3A

EXPERIMENTAL

10\^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If no safety threshold is met (halting conditions) proceed to Cohort 3B. N = 18

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Cohort 3B

EXPERIMENTAL

10\^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. N = 18

Biological: Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Other: Placebo

Interventions

Influenza RG-A/Texas/71/2017 (H3N2) Challenge BIOLOGICAL

RG-A/Texas/71/2017 (H3N2) is an infectious influenza virus and requires handling at BioSafety Level 2. The challenge virus will be administered intranasally in a volume of approximately 0.5 mL per nostril. Intranasal challenge will be carried out using the Intranasal Mucosal Atomization ( MAD Nasa(TM)) Device attached to a 1 mL syringe.

Cohort 1A; Cohort 1B; Cohort 1C; Cohort 2A; Cohort 2B; Cohort 2C; Cohort 3A; Cohort 3B

Placebo OTHER

Sucrose phosphate glutamate (SPG) inoculum

Cohort 1A; Cohort 1B; Cohort 1C; Cohort 2A; Cohort 2B; Cohort 2C; Cohort 3A; Cohort 3B

Eligibility Criteria

• Age: 18 Years - 45 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 Reverse Transcription - Polymerase Chain Reaction (RT-PCR) beginning on Study Day 6
• No viral shedding is defined as two negative RT-PCR tests 12 or more hours apart
• Healthy\* males and non-pregnant, non-breastfeeding females aged \> / = 18 and \< 46 years of age at enrollment
• 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
• Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement with history of documented radiological confirmation test at least 90 days after the procedure).
• True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the influenza challenge virus, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. Must use at least one acceptable primary form of contraception for at least 30 days prior to challenge and at least one acceptable primary form of contraception during the remainder of the study or approximately 57 days after confinement.
• NOTE: These criteria are applicable to female subjects in a heterosexual relationship AND of child-bearing potential. These criteria do not apply to subjects in a same sex relationship.
• Non-habitual smoker\* of tobacco, e-cigarettes or marijuana
• \*Non-habitual smokers are those who smoke no more than four cigarettes, other tobacco products, e-cigarettes (to include vaping and Juuling products) or marijuana in a week and agree not to smoke cigarettes, other tobacco products, e-cigarettes and/or marijuana products during participation in the study.
• 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 for at least one week before admission and throughout the confinement period
• Negative drug urine toxicology result on screening (i.e., amphetamines, cocaine, and opiates) and on admission to the confinement unit (i.e., amphetamines, cocaine, and opiates)\*

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
• Saturation of Peripheral Oxygen (SpO2) \>/= 95%; Respiratory Rate (RR) \</= 18
• Oral temperature is less than 100.6 degrees Fahrenheit
• Eligibility laboratory values White Blood Cell (WBC), Absolute Lymphocyte Count, Hemoglobin (Hgb), Platelets (PLTs), Alanine Transaminase (ALT) and Creatinine(Cr) are within acceptable parameters\*
• \*Labs within normal range or grade 1 abnormalities deemed not clinically significant by a study investigator are considered acceptable
• Body mass index (BMI) \> 18.5 and \< 40 kg/m2 at screening
• Other screening tests Electrocardiogram (ECG) and Chest x-ray(CXR) are within normal reference range or not deemed clinically significant by the Principle Investigator(PI) or appropriate sub-investigator\*
• \*Designated clinician licensed to make medical diagnoses and listed on the Form FDA 1572
• Negative test for Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) at screening
• Negative respiratory virus panel by BIOFIRE(R) FILMARRAY(R) respiratory panel by bioMérieux or by Luminex xTAG(R) on Day -2, and Day -1
• Negative RT-PCR test for severe acute respiratory syndrome coronavirus 2(SARS-CoV 2) on screening and Day -2
• Hemagglutination Inhibition Test (HAI) antibody titer \</=1:40 against influenza A/Texas/71/2017 (H3N2) at screening

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-4606, United States

Location

Duke University Trent Drive

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Christopher Woods
• Organization: Duke University Medical Center

chris.woods@duke.edu

919-684-7916

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 27, 2021
• Study Start: August 19, 2021
• Primary Completion: September 22, 2022
• Study Completion: September 22, 2022
• Last Updated: August 28, 2025
• Results First Posted: November 30, 2023

Record last verified: 2023-07-25

Locations

US (2)