Safety and Effectiveness of a Seasonal Live Attenuated Influenza Vaccine in a Human Challenge Model of Infection With Wild-type (wt) Influenza A/California/2009 (H1N1)-Like Virus

NCT02950688 | Withdrawn Phase 1 DMC

• 1 other identifier: URMC 15-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the immune response produced by a seasonal live attenuated influenza vaccine (LAIV) when compared to placebo. The initial vaccination will be followed 2 months later by an inpatient trial evaluating safety, infectivity, clinical response, and viral shedding after exposure to the wild-type A/California/2009-like influenza challenge virus.

Conditions

Influenza, Human

Outcome Measures

Primary Outcomes (11)

• Frequency of any reactogenicity events after administration of seasonal LAIV

  Measured through Day 180

• Frequency of significant increases in nasal secretion hemagglutination (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)

  Measured through Day 84

• Frequency of instances of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT)

  Measured on Day 28 after immunization

• Frequency of detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay

  Measured on Day 7 following vaccination

• Frequency of challenge virus shedding on one or more days on Days 56-63 as assessed by culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR)

  Measured through Day 63

• A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by HAI assays

  Measured through Day 56

• A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by MN assays

  Measured through Day 56

• A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by blood serum titer

  Measured through Day 56

• Clinical symptoms recording of 10 key influenza symptoms (cough, sore throat, stuffy nose, dyspnea, fatigue, headache, myalgias, nausea, diarrhea, and feverishness) on an analog scale of severity

  Measured through Day 180

• Area under the curve (AUC) of symptom severity

  Measured through Day 180

• Total nasal mucus weight

  Nasal mucus weights will be determined by collecting tissues over 24 hours, weighing them and subtracting the dry weight.

  Measured through Day 180

Study Arms (2)

Group 1: Seasonal LAIV

EXPERIMENTAL

Participants will receive 1 dose of seasonal LAIV on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56.

Biological: Seasonal LAIV; Biological: Wild-type A/California/2009-like Influenza Virus

Group 2: Placebo

PLACEBO COMPARATOR

Participants will receive 1 dose of placebo on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56.

Biological: Placebo; Biological: Wild-type A/California/2009-like Influenza Virus

Interventions

Seasonal LAIV BIOLOGICAL

10\^7.0 fluorescent focus units (FFU); administered by intranasal spray

Also known as: FluMist Quadrivalent®

Group 1: Seasonal LAIV

Placebo BIOLOGICAL

Administered by intranasal spray

Group 2: Placebo

Wild-type A/California/2009-like Influenza Virus BIOLOGICAL

Approximately 3.5 x 10\^6 TCID50; administered intranasally

Group 1: Seasonal LAIV; Group 2: Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult males and non-pregnant females between 18 years and 45 years of age. Children will not be recruited or enrolled in this study for safety considerations and because of the need for isolation.
• General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
• Likely to be susceptible to the challenge virus as determined by a baseline serum HAI antibody titer to the A/California/09 wild-type virus of 1:8 or less.
• Agree to storage of blood specimens for future research.
• Available for the duration of the trial.
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Female subjects must agree to use effective birth control methods for the duration of the study (for example, pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse, surgical sterilization). All female subjects will be considered being of child-bearing potential except those who have undergone hysterectomy and those in whom menopause occurred at least 1 year prior to the study.

You may not qualify if:

• Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test.
• Currently breast-feeding.
• Body Mass Index (BMI) of less than 18.5 or greater than 40.
• Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
• Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
• Other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
• History of anaphylaxis.
• Allergy to oseltamivir as determined by subject report.
• Current diagnosis of asthma or reactive airway disease (within the past 2 years).
• History of Guillain-Barré Syndrome.
• Known immunodeficiency syndrome.
• Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination.
• Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination.
• Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) or any unlicensed vaccine within 6 months of enrollment.
• History of a surgical splenectomy.

Sponsors & Collaborators

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

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, 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

Study Officials

• John Treanor, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: November 1, 2016
• Primary Completion: December 1, 2020
• Last Updated: November 29, 2017

Record last verified: 2017-11

Locations

US (1)