Evaluation of Human Immune Responses to Influenza Virus Vaccination in Healthy Volunteers

NCT02385123 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: 14-0071HHSN272201400004C
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants, with the aim of enrolling up to 70 participants. This study enrolled males and non-pregnant females, 18-49 years old, inclusive. The participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Total enrollment was 60 participants. Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. The study enrolled a total 60 participants. The primary objective of the study was to characterize HA-specific plasmablasts and memory B cells after influenza vaccination. Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.

Conditions

Influenza; Influenza Immunisation

Keywords

ex-vivo; Healthy Volunteers; Immune Response; Influenza; plasmablasts; Vaccine

Outcome Measures

Primary Outcomes (2)

• Percentage of Subjects Achieving Seroconversion (Pre-vaccination Hemagglutination Inhibition (HI) Titer <1:10 and a Post-vaccination HI Titer >1:40 or a Pre-vaccination HI Titer >1:10 and a Minimum Four-fold Rise in Post-vaccination HI Antibody Titer)

  Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using receptor destroying enzyme (RDE)-treated plasma and turkey red blood cells following the World Health Organization (WHO) standard protocol. For influenza B, guinea pig red blood cells were used instead.

  Day 28

• Percentage of Subjects With Pre-vaccination Titer <1:40

  Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using RDE-treated plasma and turkey red blood cells following the WHO standard protocol. For influenza B, guinea pig red blood cells were used instead.

  Day 0

Secondary Outcomes (21)

• Endpoint Immunoglobulin G (IgG) Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein

  Day 0

• Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein

  Day 180

• Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein

  Day 28

• Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region

  Day 0

• Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region

  Day 180

Study Arms (1)

Seasonal Flu Vaccine/Healthy Adult Volunteers

EXPERIMENTAL

0.5 ml of seasonal inactivated influenza vaccine (IIV) was administered intramuscularly (IM) on Day 0 of each study season, for this multi-year study. A total of 60 participants were enrolled in this study.

Biological: Influenza Virus Vaccine Inactivated

Interventions

Influenza Virus Vaccine Inactivated BIOLOGICAL

A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season.

Seasonal Flu Vaccine/Healthy Adult Volunteers

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects between 18 and 49 years of age, inclusive.
• Subjects capable of providing written informed consent prior to initiation of any study procedures. Subjects able to understand and comply with planned study procedures and be available for all study visits.
• Screening labs within normal limits per the local laboratory normal ranges or considered to be not clinically significant by the investigator. Normal laboratory ranges are as listed below:
• Hematology:
• Hemoglobin: Male- 12.9-16.1 gm/dL, Female- 11.4-14.4 gm/dL
• White blood cells (WBC): Male- 4.2-9.2 upper limit (uL), Female- 4-10 upper limit (uL)
• Platelet count: 150-400 upper limit (uL)
• Chemistries:
• Kidney function: Glomerular filtration rate (GFR) \> / = 60 mL/min/1.73 m\^2;
• Liver enzymes: Albumin \> / = 3.5 g/dL; alanine aminotransferase (ALT) \<66 U/L; aspartate aminotransferase (AST) \<62 U/L
• Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season.
• Female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit, enrollment visit and all subsequent study visits longer than 14 days since the last pregnancy test.

You may not qualify if:

• Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). This information will be obtained verbally from the patient.
• If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
• Chronic medical conditions that cause immunodeficiency or that require medications which could alter immune function such as immunosuppressants and immunoenhancers.
• Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation. This includes any chronic medical disease or condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study
• Have an acute illness, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
• Persons taking anticoagulants, long-term aspirin therapy, or long-term systemic steroids (greater than 3 months in the past 12 months and any within 30 days).
• Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the study vaccine;
• Have a known latex allergy;
• Have a history of severe reactions following previous immunization with licensed influenza virus vaccines.
• Have a history of Guillain-Barre syndrome.
• Subjects who had or are suspected to have had an influenza infection in the current influenza season.
• Subjects who, at screening, have abnormal vital signs and/or physical exam, including a temperature \> / = 38.0 C, Systolic blood pressure \< / = 90 or \> / = 160 mmHg, pulse \< / = 60 or \> 110 beats per minute, new rash, signs of infection.
• Subjects who have already received the seasonal influenza vaccine in the current influenza vaccination season.

Sponsors & Collaborators

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

Study Sites (1)

Emory University Hospital - W. Dean Warren General Clinical Research Center (GCRC)

Atlanta, Georgia, 30322-1059, United States

Location

Related Publications (4)

• Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.

  PMID: 12517228 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014. MMWR Recomm Rep. 2013 Sep 20;62(RR-07):1-43.

  PMID: 24048214 BACKGROUND

• Kunzel W, Glathe H, Engelmann H, Van Hoecke C. Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time. Vaccine. 1996 Aug;14(12):1108-10. doi: 10.1016/0264-410x(96)00061-8.

  PMID: 8911005 BACKGROUND

• Pica N, Palese P. Toward a universal influenza virus vaccine: prospects and challenges. Annu Rev Med. 2013;64:189-202. doi: 10.1146/annurev-med-120611-145115.

  PMID: 23327522 BACKGROUND

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due to the COVID-19 pandemic, all non-essential research was halted at our site (mid-March 2020). New enrollments and follow-up visits were halted, impacting the timing of participants' subsequent follow-up visits. There were participants whose Day 180 visits (final visits) were impacted. We requested an expansion of the Day 180 visit window. Due to the ongoing pandemic, our site was unable to resume participant research activities for this study, which closed to accrual on 3/31/2020.

Results Point of Contact

• Title: Rafi Ahmed, PhD
• Organization: Emory University

rahmed@emory.edu

404-727-3571

Study Officials

• Aneesh Mehta, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 11, 2015
• Study Start: April 1, 2015
• Primary Completion: December 6, 2019
• Study Completion: December 31, 2020
• Last Updated: October 25, 2023
• Results First Posted: October 25, 2023

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)