Evaluation of Anti-Hemagglutinin (Anti-HA) Antibodies as Protection From the Flu in Healthy People

NCT01971255 | Completed Phase 1 Results DMC

• 2 other identifiers: 13021513-I-0215
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Researchers want to know if a certain type of antibody in the blood affects whether people get influenza (the flu). They will study 2 different groups with different levels of anti-HA antibodies and expose them to the flu virus. They will study how the flu develops in a healthy person. This may lead to future studies to develop new vaccines and treatments for the flu. Objective: \- To study how people can be protected from flu infection. Eligibility: \- Healthy volunteers 18 to 50 years of age. Design:

• Participants will be screened through the use of a medical history, physical exam, and laboratory tests.
• Groups of 7 participants will stay in an isolation unit in a hospital for at least 9 days with no visitors.
• Participants will be screened again upon admission. They will also have:
• ECG: soft electrodes will be stuck to the skin. A machine will record the heart s electrical signals.
• Echocardiogram: a small probe will be held to the chest to take pictures of the heart.
• Lung tests: participants will blow into a machine.
• They will also have nasal fluid collected. This will be done either with a swab or with a tube of water washing out the nose. This will be done once every day.
• The flu virus will be sprayed into the participant s nose. This will be done only once.
• Participants will complete a questionnaire on day 1 and twice a day after that for 14 days.
• A medical team will watch participants 24 hours a day. They will go home after 2 days of negative flu tests.
• Participants will have 4 follow-up visits over 8 weeks.

Conditions

Influenza

Keywords

Influenza A; HAI; H1N1; Challenge Study; Correlates of Protection

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Mild to Moderate Influenza Disease (MMID)

  This was determined by presence of the combination of symptoms of influenza and presence of a positive clinical test for influenza. If both were present then the participant had positive MMID.

  Within 10 days of inoculation

Secondary Outcomes (5)

• Clinical Disease Severity Score

  Within 28 days after inoculation

• Duration of Shedding (Days)

  Within 14 days of inoculation

• Duration of Symptoms (Days)

  within 68 days after inoculation

• Number of Symptoms

  within 68 days after inoculation

• Number of Participants With Influenza Symptoms

  within 68 days after inoculation

Study Arms (2)

High Titer (HAI > or = 1:40)

EXPERIMENTAL

Subjects with prechallenge hemagglutination inhibition (HAI) titers of ≥1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r 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.

Biological: Ca/04/2009/H1N1r Challenge Virus

Low Titer (HAI < 1:40)

EXPERIMENTAL

Subjects with prechallenge hemagglutination inhibition (HAI) titers of \<1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r 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.

Biological: Ca/04/2009/H1N1r Challenge Virus

Interventions

Ca/04/2009/H1N1r 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.

High Titer (HAI > or = 1:40); Low Titer (HAI < 1:40)

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 nonchildbearing 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 (HAI) titer against the challenge virus of greater than or equal to 1:40 or less than or equal to 1:10 during a screening visit in protocol #11-I-0183
• HIV uninfected.
• 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).

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)

• Potter CW, Oxford JS. Determinants of immunity to influenza infection in man. Br Med Bull. 1979 Jan;35(1):69-75. doi: 10.1093/oxfordjournals.bmb.a071545. No abstract available.

  PMID: 367490 BACKGROUND

• Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg (Lond). 1972 Dec;70(4):767-77. doi: 10.1017/s0022172400022610.

  PMID: 4509641 BACKGROUND

• Cox RJ. Correlates of protection to influenza virus, where do we go from here? Hum Vaccin Immunother. 2013 Feb;9(2):405-8. doi: 10.4161/hv.22908. Epub 2013 Jan 4.

  PMID: 23291930 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

• Han A, Poon JL, Powers JH 3rd, Leidy NK, Yu R, Memoli MJ. Using the Influenza Patient-reported Outcome (FLU-PRO) diary to evaluate symptoms of influenza viral infection in a healthy human challenge model. BMC Infect Dis. 2018 Jul 28;18(1):353. doi: 10.1186/s12879-018-3220-8.

  PMID: 30055573 DERIVED

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 James 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
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: October 29, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 24, 2017
• Results First Posted: April 24, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)