pH1N1 Blinded Challenge Study

NCT07110532 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 23-001175N93019C00055
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

This protocol describes a clinical trial to develop and validate a Controlled Human Infection Model (CHIM) for influenza A/Arkansas/08/2020 (pH1N1). The study is designed to determine the optimal infectious dose of the pH1N1 challenge strain for use in future clinical trials evaluating influenza countermeasures. The study will enroll and challenge adult volunteers with the pH1N1 influenza virus challenge or sham inoculations. Given the adaptive design of this trial, the potential number of participants can vary. Depending on the pathway recommended by the PSRT and followed in the Trial Schema, the study population can range from around 30 to 99. The anticipated final sample size will be approximately 90 receiving pH1N1 challenge product plus and 6 persons receiving a sham inoculation. Participants will be pre-screened for health and for serological HAI antibody titers of \</1:40 against the challenge strain. Eligible participants will be enrolled sequentially into challenge cohorts and will be randomly assigned to receive a single dose of either sham inoculation or the interventional study product at a dose between 10\^6 to 10\^7 TCID50 (or 10\^5 TCID50 if needed). Dose titration will be conducted under an adaptive escalation schedule whereby dosing will start at 10\^6 TCID50 and escalate to the next dose if a pre-determined symptomatic influenza attack rate and clinical symptom score thresholds are not met and if the dose is determined to be safe with no pre-defined halting criteria being met. The primary objectives of this study are to determine the optimal infectious dose of a pH1N1 viral challenge to cause laboratory-confirmed clinical influenza and to assess the safety profile of pH1N1 viral challenge.

Conditions

Influenza

Keywords

challenge; Double-blind; Influenza; Influenza A; pH1N1; Random

Outcome Measures

Primary Outcomes (5)

• Number and percentage of participants reporting a related SAE at any time from the time of the first challenge inoculation.

  Through Day 57

• Number and percentage of participants reporting any related AE from the time of the first challenge inoculation.

  Through Day 29

• Number and percentage of participants with symptomatic influenza virus infection.

  "Symptomatic influenza virus infection" is defined as meeting both of these criteria: 1. Viral shedding detected in NP swab specimens by qualitative RT-PCR; and 2. A cumulative symptom score \>/=6 using a Modified Jackson Score.

  Day 2 through Day 6

• Number of related adverse events (AE) reported from the time of the first challenge inoculation.

  Through Day 29

• Number of related serious adverse events (SAE) from the time of the first challenge inoculation.

  Through Day 57

Secondary Outcomes (10)

• Duration of viral shedding quantified by number of days of qualitative RT-PCR influenza detections in NP swab samples

  Day 2 through Day 6

• Geometric Mean Fold Rise (GMFR).

  Day 6 through 29

• Geometric Mean Titers (GMTs).

  Day 6 through 29

• HAI and MN antibody geometric mean titers (GMTs) at baseline.

  Before Day 0

• Investigator-assessed clinical symptoms as measured by Modified Jackson Score, post challenge through antiviral administration.

  Through Day 6

Study Arms (12)

Cohort 1A

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus (RG) -A/Arkansas/08/2020 (pH1N1) at a dose of 10\^6 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the Protocol Safety Review Team (PSRT) agrees that the dose is safe then Cohort 1B and Cohort 2A will begin. If proven unsafe the dose will be de-escalated to Cohort XA. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 1B

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus (RG) -A/Arkansas/08/2020 (pH1N1) at a dose of 10\^6 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the PSRT agrees that the dose is safe then Cohort 1C and Cohort 2A will begin. If proven unsafe the dose will be de-escalated to Cohort XA. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 1C

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus (RG) -A/Arkansas/08/2020 (pH1N1) at a dose of 10\^6 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the PSRT agrees that the dose is safe then Cohort 2A will begin. If proven unsafe the dose will be de-escalated to Cohort XA. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 2A

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus (RG) -A/Arkansas/08/2020 (pH1N1) at a dose of 10\^7 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the PSRT agrees that the dose is safe then Cohort 2B will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 2B

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^7 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the PSRT agrees that the dose is safe then Cohort 2C will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 2C

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^7 TCID50. One of the subjects will receive a sham dose of 0 TCID50. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 3A

EXPERIMENTAL

Subjects will randomly be administered two inoculations of intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^5 TCID50 administered 2-5 hours apart. If the PSRT agrees that the dose is safe, then Cohort 3B will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 3B

EXPERIMENTAL

Subjects will randomly be administered two inoculations of intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^7 TCID50 administered 2-5 hours apart. If the PSRT agrees that the dose is safe, then Cohort 4 will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort 4

EXPERIMENTAL

Subjects will randomly be administered two inoculations of intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^6 TCID50 administered 2-5 hours apart. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort XA

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^5 TCID50. One of the subjects will receive a sham dose of 0 TCID50. De-escalation will occur after PSRT review of Cohort 1A, Cohort 1B, and Cohort 1C. If the PSRT agrees that the dose is safe then Cohort XB will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort XB

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^5 TCID50. One of the subjects will receive a sham dose of 0 TCID50. If the PSRT agrees that the dose is safe then Cohort XC will begin. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Cohort XC

EXPERIMENTAL

Subjects will randomly be administered a single intranasal virus, (RG) -A/Arkansas/08/2020 (pH1N1), at a dose of 10\^5 TCID50. One of the subjects will receive a sham dose of 0 TCID50. N=30

Biological: A/Arkansas/08/2020 (pH1N1); Other: Sham/Diluent (1X SPG+Arg+Gel)

Interventions

A/Arkansas/08/2020 (pH1N1) BIOLOGICAL

GMP-grade, cell-based influenza A (pH1N1) virus (Lot #24-005), derived via reverse genetics for use in controlled human infection studies.

Cohort 1A; Cohort 1B; Cohort 1C; Cohort 2A; Cohort 2B; Cohort 2C; Cohort 3A; Cohort 3B; Cohort 4; Cohort XA; Cohort XB; Cohort XC

Sham/Diluent (1X SPG+Arg+Gel) OTHER

Sterile diluent containing 1X Sucrose Phosphate Glutamate (SPG), 1% arginine, and 1% hydrolyzed gelatin, used as a sham comparator in the human challenge trial.

Cohort 1A; Cohort 1B; Cohort 1C; Cohort 2A; Cohort 2B; Cohort 2C; Cohort 3A; Cohort 3B; Cohort 4; Cohort XA; Cohort XB; Cohort XC

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provides signed and dated informed consent form prior to the initiation of any trial procedures.
• Able to understand and agrees to comply with all planned trial procedures and to be available for all study visits.
• Age \>/= 18 and \</= 55 years at time of enrollment.
• Must agree to collection of venous blood and nasal absorption specimens per protocol and enrollment in DMID 19-0025 biorepository protocol for use of residual/repository research blood specimens.
• In good general health.\*

You may not qualify if:

• Able to take oral medication and willing to receive oseltamivir phosphate and/or baloxavir marboxil as part of the study.
• Participants of childbearing potential\* agree to the use of acceptable forms of contraception\*\* for at least 30 days prior to enrollment and agree to use such a method during study participation.
• \*Childbearing potential in a participant is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year since last menses if menopausal.
• \*\*Acceptable forms of primary contraception include true abstinence (100% of time no insertional sexual intercourse), or, if heterosexual intercourse is anticipated, monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to enrollment, intrauterine devices, birth control pills, condoms, and injectable/implantable/insertable/transdermal hormonal birth control products. Must use at least one acceptable form of contraception for at least 30 days prior to enrollment and through study completion.
• Non-smoker or non-habitual smoker\* of tobacco, e-cigarettes, or marijuana
• \*A non-habitual smoker is a person who smokes no more than four cigarettes, other tobacco products, e-cigarettes (to include vaping and Juul products), and/or marijuana in a week.
• No self-reported or known history of alcoholism within the 2 years prior to enrollment.
• No self-reported or known history of illicit drug use for at least 30 days prior to enrollment.
• Agrees not to use the listed prescription or over the counter medications\* within 7 days prior to confinement and through the confinement period\*\*.
• \*Oseltamivir, zanamivir, peramivir, baloxavir marboxil, amantadine, rimantadine, aspirin, intranasal steroids, decongestants, antihistamines, and non-steroidal anti-inflammatory drugs (NSAIDs)
• \*\*An exception can be made with the approval of the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572
• Screening pulse is 55 to 100 beats per minute, inclusive\*
• \*Screening pulse values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.
• Screening systolic blood pressure is 90 to 140 mmHg, inclusive\*
• \*Screening systolic blood pressure values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.

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, 21201-1509, United States

RECRUITING

Duke Vaccine and Trials Unit

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Meagan Deming

CONTACT

14107068333; mdeming@som.umaryland.edu

Study Design

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

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: August 7, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): August 18, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04-01

Locations

US (2)