Intradermal Influenza Vaccine in the Young

Intradermal Trivalent Influenza Vaccine in Young Adults, a Double-blind Randomized Controlled Trial

Influenza poses a heavy burden to our health service. The WHO estimates that seasonal influenza causes 250,000-500,000 deaths worldwide each year. Various strategies including intradermal vaccination and new vaccine adjuvants have been shown to improve immunogenicity. Recently, imiquimod, a synthetic Toll-like receptor 7 (TLR7) agonist useful for the treatment of DNA virus infection, have been shown to improve vaccine immunogenicity against influenza virus in mouse model. The objective of this prospective double-blind randomized controlled trial is to evaluate the effect and safety of topical treatment with imiquimod immediately before intradermal influenza vaccination in healthy young adults.

Study Overview

• Status: Completed
• Conditions: Influenza Viral Infections
• Intervention / Treatment: Drug: Imiquimod ointment; Biological: Intradermal influenza vaccine; Drug: Aqueous cream; Biological: Intramuscular influenza vaccine

Detailed Description

Influenza poses a heavy burden to our health service. Seasonal, zoonotic and pandemic influenza are constant global threats. The WHO estimates that seasonal influenza causes 250,000-500,000 deaths worldwide each year, with an even higher mortality during the pandemic periods. Moreover zoonotic influenza such as the avian-origin H5N1 and more recently the H7N9 influenza are associated with a much higher mortality than seasonal influenza. Vaccine immunogenicity among elderly individuals is also suboptimal due to immunosenescence. Various strategies including intradermal vaccination and new vaccine adjuvants have been shown to improve immunogenicity.

Recently, imiquimod, a synthetic Toll-like receptor 7 (TLR7) agonist useful for the treatment of DNA virus infection, have been shown to improve vaccine immunogenicity against influenza virus in both mouse model. The objective of this prospective double-blind randomized controlled trial is to evaluate the effect and safety of topical treatment with imiquimod immediately before intradermal influenza vaccination. Our a priori hypothesis is that imiquimod pretreatment would expedite and augment the immunogenicity of influenza vaccination.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • The University of Hong Kong, Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult patients at the age of 18-30 years and given written informed consent
• Subjects must be available to complete the study and comply with study procedures.
• Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.

Exclusion Criteria:

• Clinically significant immune-related diseases or significant recent co-morbidities
• Inability to comprehend and to follow all required study procedures
• History or any illness that might interfere with the results of the study or pose additional risk to the subjects due to participation in the study
• Have received trivalent influenza vaccine within the same year
• Have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
• Have a known allergy to eggs or other components of the Study Vaccines (including gelatin, formaldehyde, octoxinol, thimerosal, and chicken protein), or history of any anaphylaxis, serious vaccine reactions, to any excipients.
• Have a positive urine or serum pregnancy test within 24 hours prior to vaccination, or women who are breastfeeding.
• Female of childbearing potential, not using any acceptable contraceptive methods for at least 2 months prior to study entry or that do not plan to use acceptable birth control measures during the first 3 weeks after vaccination.
• Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
• Have an active neoplastic disease or a history of any hematologic malignancy.
• Have long-term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed).
• Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
• Have known active human immunodeficiency virus (HIV), Hepatitis C infection or autoimmune hepatitis and cirrhosis.
• Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
• History of progressive or severe neurological disorders Have received any licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 21 days following the second vaccination (only exception being unadjuvanted seasonal influenza vaccines which are allowed until 1 week prior to and after 1 week study vaccinations).
• Axillary temperature ≥ 38°C or oral temperature ≥ 38.5°C within 3 days of intended study vaccination
• Surgery planned during the study period that in the Investigator's opinion would interfere with the study visits schedule
• Have a history of alcohol or drug abuse in the last 5 years.
• Have a history of Guillain-Barré Syndrome. Have any condition that the investigator believes may interfere with successful completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ID TIV + imiquimod; imiquimod ointment followed by intradermal influenza vaccine	Drug: Imiquimod ointment; 5% 250mg imiquimod ointment; Other Names: Aldara; Biological: Intradermal influenza vaccine; intradermal trivalent influenza vaccine (Intanza15)
Sham Comparator: ID sham + imiquimod; imiquimod ointment followed by sham intradermal influenza vaccine	Drug: Imiquimod ointment; 5% 250mg imiquimod ointment; Other Names: Aldara
Active Comparator: IM TIV + aq; aqueous cream followed by intramuscular influenza vaccine	Drug: Aqueous cream; aqueous cream; Other Names: Aqueous cream BP; Biological: Intramuscular influenza vaccine; intramuscular trivalent influenza vaccine (Vaxigrip)
Active Comparator: ID TIV + aq; aqueous cream followed by intradermal influenza vaccine	Biological: Intradermal influenza vaccine; intradermal trivalent influenza vaccine (Intanza15); Drug: Aqueous cream; aqueous cream; Other Names: Aqueous cream BP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rate	Hemagglutination inhibition assay	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection rate	Hemagglutination inhibition assay	Day 7
GMT fold increase	Hemagglutination inhibition assay	Day 7
GMT	Microneutralization antibody assay	Day 7
Seroconversion rate	Hemagglutination inhibition assay	Day 21
Seroprotection rate	Hemagglutination inhibition assay	Day 21
GMT fold increase	Hemagglutination inhibition assay	Day 21
GMT	Microneutralization antibody assay	Day 21
Adverse events	Solicited local and systemic adverse reactions monitored from time of vaccination till day 7.	Day 7

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Study Chair: Kwok-Yung Yuen, MD FRCP, The University of Hong Kong

Publications and helpful links

General Publications

• Hung IF, Zhang AJ, To KK, Chan JF, Li P, Wong TL, Zhang R, Chan TC, Chan BC, Wai HH, Chan LW, Fong HP, Hui RK, Kong KL, Leung AC, Ngan AH, Tsang LW, Yeung AP, Yiu GC, Yung W, Lau JY, Chen H, Chan KH, Yuen KY. Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial. Lancet Infect Dis. 2016 Feb;16(2):209-18. doi: 10.1016/S1473-3099(15)00354-0. Epub 2015 Nov 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Estimate): December 5, 2014
• Last Update Submitted That Met QC Criteria: December 3, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Virus Diseases; Influenza, Human; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Vaccines; Imiquimod
• Other Study ID Numbers: UW 14-016