Back to resultsIntradermal Influenza Vaccine With Topical Imiquimod in Elderly and Chronic Illness Patients
Primary Purpose
Influenza
Status
Unknown status
Phase
Phase 3
Locations
Hong Kong
Study Type
Interventional
Intervention
Vaxigrip tetra
Fluzone high-dose
Aldara 5% Topical Cream
Aqueous cream BP
Sponsored by
About this trial
This is an interventional prevention trial for Influenza focused on measuring influenza, intradermal, imiquimod, high-dose, vaccine
Eligibility Criteria
Inclusion Criteria:
- Recruited subjects include subjects ≥50 years or adult subjects ≥18 years with chronic illness attending GOPD or SOPD in HKWC.
- All subjects/ next of kin give 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:
- Inability to comprehend and to follow all required study procedures.
- 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 an active neoplastic disease or a history of active hematologic malignancy.
4. Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
6. Have known active human immunodeficiency virus (HIV) infection. 7. Received an agent on clinical trial (vaccine, drug, 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.
8. Tympanic temperature ≥ 38°C within 3 days of intended study vaccination 9. Have a history of alcohol or drug abuse in the last 5 years. 10. Have a history of Guillain-Barré Syndrome. 11. Pregnant during the study period. 12. Have any condition that the investigator believes may interfere with successful completion of the study.
Sites / Locations
- University of Hong Kong, Queen Mary HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
IQ
IM
HD
Arm Description
Year 1: a single dose ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream Year 2: randomised into 3 subgroups. Group IQ1: ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream Group IQ2: IM QIV (15 µg of hemagglutinin per strain with pre-treatment of the injected skin with aqueous cream. Group IQ3: ID normal saline vaccination with pre-treatment of the injected skin with imiquimod (Aldara) cream. Year 3: IQ1 and IQ2 same treatment as second year. IQ3 same as first year.
Year 1: a single dose IM QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream Year 2: randomised into 3 subgroups. Group IM1: IM QIV (15 µg of hemagglutinin per strain with pre-treatment of the injected skin with aqueous cream. Group IM2: ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream. Group IM3: IM normal saline vaccination with aqueous cream pretreatment. Year 3: IM1 and IM2 same treatment as second year. IM3 same as first year.
Year 1: a single high-dose IM TIV (60 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream Year 2: Group HD1: IM QIV (60 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream. Group HD2: IM normal saline vaccination with aqueous cream pretreatment. Year 3: Group HD1 same treatment as second year. HD2 same as first year.
Outcomes
Primary Outcome Measures
Mortality
death rate
Overall hospitalisation
hospitalisation rate for all diagnosis
Hospitalisation for influenza
hospitalisation rate with microbiological confirmation of influenza
Hospitalisation for pneumonia
hospitalisation rate with a clinical diagnosis of pneumonia
Secondary Outcome Measures
immediate adverse events
immediate adverse events
adverse events
Local: redness, swelling, induration, pain and ecchymosis. Redness, swelling, and induration will be graded based on size: Grade 1, under 20mm; Grade 2, 20-50mm. Pain will be graded as follows: Grade 1, pain on touch, Grade 2, pain when arm is moved Systemic: fever, headache, malaise, myalgia, arthralgia and severe adverse events.
immunogenicity
GMT, seroconversion rate, seroprotection rate and GMT fold increase by HI and MN assays on day, 21, 6 months and 1 year
Full Information
NCT ID
NCT04143451
First Posted
October 18, 2019
Last Updated
April 27, 2021
Sponsor
The University of Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT04143451
Brief Title
Intradermal Influenza Vaccine With Topical Imiquimod in Elderly and Chronic Illness Patients
Official Title
Intradermal Quadrivalent Influenza Vaccine With Topical Imiquimod in Elderly & Chronic Ill Subjects, a Double-Blind Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 23, 2019 (Actual)
Primary Completion Date
September 30, 2022 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Hong Kong
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To compare the safety and clinical efficacy (death, overall hospitalization, hospitalization for influenza or pneumonia) of ID QIV delivered via an intradermal device with imiquimod cream pretreatment with conventional intramuscular (IM) standard dose QIV and IM high-dose TIV
Detailed Description
This is a prospective; double-blind randomized controlled study performed in the HKWC. Recruited subjects include subjects ≥50 years and adult subjects ≥18 years with chronic illness. Eligible subjects will be randomly allocated (3:3:2) into one of the three groups in the first year. Group IQ: topical 5% 250mg imiquimod ointment followed by intradermal QIV, Group IM: topical aqueous-cream followed by IM QIV and Group HD: topical aqueous-cream followed by intramuscular high-dose TIV. Hemagglutination inhibition and neutralization antibody titres will be assayed. We plan to recruit 4000 subjects, 1500 subjects in each of the IQ and IM group (500 subjects in each subgroup with 3 subgroups) and 1000 subjects for the HD group (500 subjects in each subgroup with 2 subgroups).
In the following year, the IQ and IM groups will be further randomized equally into three subgroups: IQ1, IQ2 and IQ3; IM1, IM2 and IM3; and two subgroups for HD group: HD1 and HD2. Subjects randomized to IQ1, IM1 will receive the QIV with the same topical treatment, delivery mode and vaccine as the first year and HD1 will receive the TIV with the same topical treatment, delivery mode and vaccine as the first year. Subgroup IQ2 and IM2 will be vaccinated as follow: IQ2 will receive topical aqueous-cream followed by IM QIV, IM2 will receive topical imiquimod ointment followed by ID QIV. Subgroup IQ3, IM3, HD2 will receive normal saline as the vaccine for that year, but delivered by the same mode and topical treatment. In the third year, subgroups IQ1, IQ2, IM1, IM2 and HD1 will receive the same topical treatment, delivery mode and vaccine as the second year. Subgroup IQ3, IM3 and HD2 will receive the same topical treatment, delivery mode and vaccine as the first year.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
influenza, intradermal, imiquimod, high-dose, vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Double blind randomised controlled trial
Masking
ParticipantInvestigator
Masking Description
Double-blind randomization will be performed. Only the study nurse has knowledge of the type of topical treatment applied. Subjects and investigators remain blinded to the route and type of vaccination.
Allocation
Randomized
Enrollment
4000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IQ
Arm Type
Active Comparator
Arm Description
Year 1: a single dose ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream
Year 2: randomised into 3 subgroups. Group IQ1: ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream Group IQ2: IM QIV (15 µg of hemagglutinin per strain with pre-treatment of the injected skin with aqueous cream. Group IQ3: ID normal saline vaccination with pre-treatment of the injected skin with imiquimod (Aldara) cream.
Year 3: IQ1 and IQ2 same treatment as second year. IQ3 same as first year.
Arm Title
IM
Arm Type
Active Comparator
Arm Description
Year 1: a single dose IM QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream
Year 2: randomised into 3 subgroups. Group IM1: IM QIV (15 µg of hemagglutinin per strain with pre-treatment of the injected skin with aqueous cream. Group IM2: ID QIV (15 µg of hemagglutinin per strain) with pre-treatment of the injected skin with imiquimod (Aldara) cream. Group IM3: IM normal saline vaccination with aqueous cream pretreatment.
Year 3: IM1 and IM2 same treatment as second year. IM3 same as first year.
Arm Title
HD
Arm Type
Active Comparator
Arm Description
Year 1: a single high-dose IM TIV (60 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream
Year 2: Group HD1: IM QIV (60 µg of hemagglutinin per strain) with pre-treatment of the injected skin with aqueous cream. Group HD2: IM normal saline vaccination with aqueous cream pretreatment.
Year 3: Group HD1 same treatment as second year. HD2 same as first year.
Intervention Type
Biological
Intervention Name(s)
Vaxigrip tetra
Intervention Description
quadrivalent influenza vaccine
Intervention Type
Biological
Intervention Name(s)
Fluzone high-dose
Intervention Description
high-dose trivalent influenza vaccine
Intervention Type
Drug
Intervention Name(s)
Aldara 5% Topical Cream
Intervention Description
imiquimod cream
Intervention Type
Drug
Intervention Name(s)
Aqueous cream BP
Intervention Description
inactive aqueous cream
Primary Outcome Measure Information:
Title
Mortality
Description
death rate
Time Frame
3 years
Title
Overall hospitalisation
Description
hospitalisation rate for all diagnosis
Time Frame
3 years
Title
Hospitalisation for influenza
Description
hospitalisation rate with microbiological confirmation of influenza
Time Frame
3 years
Title
Hospitalisation for pneumonia
Description
hospitalisation rate with a clinical diagnosis of pneumonia
Time Frame
3 years
Secondary Outcome Measure Information:
Title
immediate adverse events
Description
immediate adverse events
Time Frame
5 minutes post vaccination
Title
adverse events
Description
Local: redness, swelling, induration, pain and ecchymosis. Redness, swelling, and induration will be graded based on size: Grade 1, under 20mm; Grade 2, 20-50mm. Pain will be graded as follows: Grade 1, pain on touch, Grade 2, pain when arm is moved Systemic: fever, headache, malaise, myalgia, arthralgia and severe adverse events.
Time Frame
7 days post vaccination
Title
immunogenicity
Description
GMT, seroconversion rate, seroprotection rate and GMT fold increase by HI and MN assays on day, 21, 6 months and 1 year
Time Frame
at 21 days, 6 months and 1 year after each vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Recruited subjects include subjects ≥50 years or adult subjects ≥18 years with chronic illness attending GOPD or SOPD in HKWC.
All subjects/ next of kin give 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:
Inability to comprehend and to follow all required study procedures.
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 an active neoplastic disease or a history of active hematologic malignancy.
4. Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
6. Have known active human immunodeficiency virus (HIV) infection. 7. Received an agent on clinical trial (vaccine, drug, 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.
8. Tympanic temperature ≥ 38°C within 3 days of intended study vaccination 9. Have a history of alcohol or drug abuse in the last 5 years. 10. Have a history of Guillain-Barré Syndrome. 11. Pregnant during the study period. 12. Have any condition that the investigator believes may interfere with successful completion of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ivan FN Hung, MD FRCP
Phone
22554049
Email
ivanhung@hku.hk
First Name & Middle Initial & Last Name or Official Title & Degree
Kelvin To, MD FRCPath
Phone
22553111
Email
kelvinto@hku.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ivan FN Hung, MD FRCP
Organizational Affiliation
The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Hong Kong, Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ivan FN Hung, MD FRCP
Phone
852 22554049
Email
ivanfn@gmail.com
First Name & Middle Initial & Last Name & Degree
Kelvin To, MD FRCPath
First Name & Middle Initial & Last Name & Degree
KY Yuen, MD FRCPath
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intradermal Influenza Vaccine With Topical Imiquimod in Elderly and Chronic Illness Patients
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