Intradermal Influenza Vaccine in the Young
Primary Purpose
Influenza Viral Infections
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Imiquimod ointment
Aqueous cream
Intradermal influenza vaccine
Intramuscular influenza vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Influenza Viral Infections
Eligibility Criteria
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.
Sites / Locations
- The University of Hong Kong, Queen Mary Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Sham Comparator
Active Comparator
Active Comparator
Arm Label
ID TIV + imiquimod
ID sham + imiquimod
IM TIV + aq
ID TIV + aq
Arm Description
imiquimod ointment followed by intradermal influenza vaccine
imiquimod ointment followed by sham intradermal influenza vaccine
aqueous cream followed by intramuscular influenza vaccine
aqueous cream followed by intradermal influenza vaccine
Outcomes
Primary Outcome Measures
Seroconversion rate
Hemagglutination inhibition assay
Secondary Outcome Measures
Seroprotection rate
Hemagglutination inhibition assay
GMT fold increase
Hemagglutination inhibition assay
GMT
Microneutralization antibody assay
Seroconversion rate
Hemagglutination inhibition assay
Seroprotection rate
Hemagglutination inhibition assay
GMT fold increase
Hemagglutination inhibition assay
GMT
Microneutralization antibody assay
Adverse events
Solicited local and systemic adverse reactions monitored from time of vaccination till day 7.
Full Information
NCT ID
NCT02103023
First Posted
March 28, 2014
Last Updated
December 3, 2014
Sponsor
The University of Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT02103023
Brief Title
Intradermal Influenza Vaccine in the Young
Official Title
Intradermal Trivalent Influenza Vaccine in Young Adults, a Double-blind Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Hong Kong
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Viral Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ID TIV + imiquimod
Arm Type
Experimental
Arm Description
imiquimod ointment followed by intradermal influenza vaccine
Arm Title
ID sham + imiquimod
Arm Type
Sham Comparator
Arm Description
imiquimod ointment followed by sham intradermal influenza vaccine
Arm Title
IM TIV + aq
Arm Type
Active Comparator
Arm Description
aqueous cream followed by intramuscular influenza vaccine
Arm Title
ID TIV + aq
Arm Type
Active Comparator
Arm Description
aqueous cream followed by intradermal influenza vaccine
Intervention Type
Drug
Intervention Name(s)
Imiquimod ointment
Other Intervention Name(s)
Aldara
Intervention Description
5% 250mg imiquimod ointment
Intervention Type
Drug
Intervention Name(s)
Aqueous cream
Other Intervention Name(s)
Aqueous cream BP
Intervention Description
aqueous cream
Intervention Type
Biological
Intervention Name(s)
Intradermal influenza vaccine
Intervention Description
intradermal trivalent influenza vaccine (Intanza15)
Intervention Type
Biological
Intervention Name(s)
Intramuscular influenza vaccine
Intervention Description
intramuscular trivalent influenza vaccine (Vaxigrip)
Primary Outcome Measure Information:
Title
Seroconversion rate
Description
Hemagglutination inhibition assay
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
Seroprotection rate
Description
Hemagglutination inhibition assay
Time Frame
Day 7
Title
GMT fold increase
Description
Hemagglutination inhibition assay
Time Frame
Day 7
Title
GMT
Description
Microneutralization antibody assay
Time Frame
Day 7
Title
Seroconversion rate
Description
Hemagglutination inhibition assay
Time Frame
Day 21
Title
Seroprotection rate
Description
Hemagglutination inhibition assay
Time Frame
Day 21
Title
GMT fold increase
Description
Hemagglutination inhibition assay
Time Frame
Day 21
Title
GMT
Description
Microneutralization antibody assay
Time Frame
Day 21
Title
Adverse events
Description
Solicited local and systemic adverse reactions monitored from time of vaccination till day 7.
Time Frame
Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kwok-Yung Yuen, MD FRCP
Organizational Affiliation
The University of Hong Kong
Official's Role
Study Chair
Facility Information:
Facility Name
The University of Hong Kong, Queen Mary Hospital
City
Hong Kong
State/Province
Hong Kong
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
26559482
Citation
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.
Results Reference
derived
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Intradermal Influenza Vaccine in the Young
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