Influenza A 2009 H1N1 Challenge Study in Healthy Adults

NCT01646138 | Completed Phase 1 Results DMC

• 2 other identifiers: 12007712-I-0077
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- A challenge study exposes a person to a disease and allows researchers to study the disease through the body's healing process. An influenza challenge study that looks at different amounts of the flu virus can provide more information on the smallest amount needed to cause an infection. Researchers want to give one dose of the Influenza A H1N1 virus to healthy volunteers to see how the body responds to the virus. Objectives:

• To find the smallest dose of Influenza A H1N1 virus that may cause a mild to moderate flu infection in a healthy adult.
• To study how the body s immune system responds to the virus. Eligibility:
• Healthy volunteers at least 18 years of age.
• Participants must be willing to remain in isolation for a minimum of 9 days. Design:
• Participants will be admitted to a hospital inpatient isolation unit. They will be screened with a physical exam and medical history. They will also have heart and lung function tests. Blood, urine, and nasal swab/wash samples will be collected.
• Participants will receive a single nasal spray of the flu virus. They will stay on the inpatient unit for at least 9 days.
• Participants will be monitored for the length of their stay. They will have frequent blood tests and other procedures as needed.
• Participants will be allowed to go home once they have had two negative tests for the virus. The tests will be given on two consecutive days....

Conditions

Influenza

Keywords

H1N1; Influenza; Human; Challenge Study; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Percent MMID

  Percent of individuals experiencing mild to moderate influenza infection (MMID, defined as active shedding and symptoms of influenza A) in each dosing group.

  67 days after influenza inoculation

Study Arms (1)

Challenge Virus

EXPERIMENTAL

The Ca/04/2009/H1N1 Vero Grown Challenge Virus was administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.

Biological: Ca/04/2009/H1N1 Vero Grown Challenge Virus

Interventions

Ca/04/2009/H1N1 Vero Grown Challenge Virus BIOLOGICAL

The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.

Challenge Virus

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Greater than or equal to 18 and less than or equal to 50 years of age.
• Agrees to not use tobacco products during participation in this study.
• Willingness to remain in isolation for the duration of viral shedding (at a minimum 9 days) and to comply with all study requirements.
• A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
• Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to and 8 weeks after administration of the influenza challenge virus. Acceptable methods of contraception include 1 or more of the following: 1) male partner who is sterile prior to the female participant s entry into the study and is the sole sexual partner for the female participant; 2) implants of levonorgestrel; 3) injectable progestogen; 4) an intrauterine device with a documented failure rate of \< 1%; 5) oral contraceptives; and 6) double barrier methods including diaphragm or condom with a spermicide.
• Willing to have samples stored for future research.
• Prechallenge serum hemagglutination-inhibition titer against the challenge strain of 1:16 or less.
• HIV uninfected.

You may not qualify if:

• Presence of self-reported or medically documented significant medical condition including but not limited to:
• Chronic pulmonary disease (e.g., asthma, emphysema).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
• Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
• Immunosuppression or ongoing malignancy.
• Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
• Postinfectious or postvaccine neurological sequelae.
• Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
• Persons greater than or equal to 65 years of age.
• Children \< 5 years of age.
• Residents of nursing homes.
• Persons of any age with significant chronic medical conditions such as:
• Chronic pulmonary disease (e.g., asthma).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
• Contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.

  PMID: 9449698 BACKGROUND

• Jameson J, Cruz J, Ennis FA. Human cytotoxic T-lymphocyte repertoire to influenza A viruses. J Virol. 1998 Nov;72(11):8682-9. doi: 10.1128/JVI.72.11.8682-8689.1998.

  PMID: 9765409 BACKGROUND

• McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe. 2007 Oct 11;2(4):240-9. doi: 10.1016/j.chom.2007.09.001.

  PMID: 18005742 BACKGROUND

• Memoli MJ, Han A, Walters KA, Czajkowski L, Reed S, Athota R, Angela Rosas L, Cervantes-Medina A, Park JK, Morens DM, Kash JC, Taubenberger JK. Influenza A Reinfection in Sequential Human Challenge: Implications for Protective Immunity and "Universal" Vaccine Development. Clin Infect Dis. 2020 Feb 14;70(5):748-753. doi: 10.1093/cid/ciz281.

  PMID: 30953061 DERIVED

• Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.

  PMID: 25416753 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

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: Matthew J. Memoli
• Organization: National Institute of Allergy and Infectious Diseases

memolim@niaid.nih.gov

+1 301 443 5971

Study Officials

• Matthew J Memoli, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)