Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures

NCT04576377 | Unknown Phase 4 DMC FDA Drug

• 2 other identifiers: BJC0331U01AI153700
• Study Type: interventional
• Target: 977
• Locations: 1 country
• Sites: 1

Brief Summary

The aims of this vaccine trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination with Flublok, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures") and participants who have poor immune responses to vaccination; and (3) to predict how influenza vaccinations and infections shape immunity.

Conditions

Influenza, Human

Outcome Measures

Primary Outcomes (2)

• Immune response to vaccination (4-fold rise in titer at day 30)

  The proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days (the targeted rise in antibody titre is defined as the proportion of participants with a four-fold or greater rise in titer, i.e. either a pre-vaccination hemagglutination inhibition titer \<10 and a post-vaccination hemagglutination inhibition titre ≥20, or a pre- vaccination hemagglutination inhibition titer ≥10 and at least a four-fold rise in post-vaccination hemagglutination inhibition antibody titer). The HAI assay has been unreliable for recent influenza A(H3N2) viruses, and if the vaccine strains or circulating strains in our study have this property we will use neutralization assays in place of HAI assays for the primary outcome for A(H3N2). Similarly, neutralization assays will be used if other influenza strains fail to hemagglutinate in the future.

  30 days after vaccination

• Immune response to vaccination (GMT ratio at day 30 and 182)

  The geometric mean titer (GMT) ratios between the vaccine group and the comparator group (placebo) against each of the vaccine strains at 30 days and 182 days

  30 days and 182 days after vaccination

Secondary Outcomes (6)

• Immune response to vaccination (antibody titer >=40 at day 30 and 182)

  30 days and 182 days after vaccination

• Immune response to vaccination (cell-mediated immunity)

  7 days and 30 days after vaccination

• Immune response to vaccination (antibody specificity)

  30 days and 182 days after vaccination

• Incidence of reactions after vaccination [Safety]

  30 days after vaccination

• Incidence of laboratory-confirmed influenza after vaccination (vaccine failure)

  One year after vaccination

Study Arms (2)

Influenza vaccination

EXPERIMENTAL

Biological: FluBlok

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

FluBlok BIOLOGICAL

Recombinant HA quadrivalent influenza vaccine (0.5mL Flublok®, Sanofi Pasteur) containing 180μg antigen, 45μg for each influenza strain included.

Influenza vaccination

Placebo OTHER

0.5mL saline placebo.

Placebo

Eligibility Criteria

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

You may qualify if:

• Aged 18-45 years at enrolment.
• Capable of providing informed consent.
• Resident in Hong Kong in the coming 2 years.

You may not qualify if:

• Vaccinated against influenza in the past 24 months.
• Included in one of the priority groups to receive influenza vaccination in Hong Kong (priority groups include pregnant women, long-stay residents of institutions for persons with disability, persons with chronic medical problems (chronic cardiovascular, lung, metabolic or kidney diseases, obesity (body mass index 30 or above) and chronic neurological condition), healthcare workers or persons working in poultry, pig farming or pig slaughtering industry).
• With diagnosed medical conditions related to their immune system.
• Currently taking medication for any condition that impairs immune system.
• Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as: Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component; moderate or severe acute illness with or without fever after any previous influenza vaccination; or a history of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.
• Individuals, who report medical conditions not suitable to receive intramuscular injection, such as bleeding disorders; habitually taking anticoagulants (with the exception of antiplatelets such as aspirin).
• Individuals who have any medical conditions not suitable to receive inactivated influenza vaccines as determined by a clinician.

Sponsors & Collaborators

• The University of Hong Kong: lead
• University of Chicago: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

The University of Hong Kong

Hong Kong, 00000, Hong Kong

Location

Related Publications (1)

• Cowling BJ, Wong SS, Santos JJS, Touyon L, Ort JT, Ye N, Kwok NKM, Ho F, Cheng SMS, Ip DKM, Peiris M, Webby RJ, Wilson PC, Valkenburg SA, Tsang JS, Leung NHL, Hensley SE, Cobey S. Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial. Clin Infect Dis. 2024 Oct 15;79(4):901-909. doi: 10.1093/cid/ciae380.

  PMID: 39041887 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

FluBlok

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 6, 2020
• Study Start: October 5, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: On publication of study results
• Access Criteria: Freely available on a public repository such as Dryad or Github

Locations

HK (1)