Intradermal Influenza Vaccine With Topical Imiquimod in Elderly and Chronic Illness Patients

Influenza Clinical Trial

Official title:

Intradermal Quadrivalent Influenza Vaccine With Topical Imiquimod in Elderly & Chronic Ill Subjects, a Double-Blind Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04143451
• Other study ID #: UW 17-372
• Status: Recruiting
• Phase: Phase 3
• Start date: October 23, 2019
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2021
• Source: The University of Hong Kong
• Contact: Ivan FN Hung, MD FRCP
• Phone: 22554049
• Email: ivanhung[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: March 31, 2023
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Recruited subjects include subjects =50 years or adult subjects =18 years with chronic illness attending GOPD or SOPD in HKWC.

2. All subjects/ next of kin give written informed consent.

3. 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:

1. Inability to comprehend and to follow all required study procedures.

2. Have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.

3. 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.

4. 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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Vaxigrip tetra
quadrivalent influenza vaccine
• Fluzone high-dose
high-dose trivalent influenza vaccine

Drug:
• Aldara 5% Topical Cream
imiquimod cream
• Aqueous cream BP
inactive aqueous cream

Locations

Country	Name	City	State
Hong Kong	University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	death rate	3 years
Primary	Overall hospitalisation	hospitalisation rate for all diagnosis	3 years
Primary	Hospitalisation for influenza	hospitalisation rate with microbiological confirmation of influenza	3 years
Primary	Hospitalisation for pneumonia	hospitalisation rate with a clinical diagnosis of pneumonia	3 years
Secondary	immediate adverse events	immediate adverse events	5 minutes post vaccination
Secondary	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.	7 days post vaccination
Secondary	immunogenicity	GMT, seroconversion rate, seroprotection rate and GMT fold increase by HI and MN assays on day, 21, 6 months and 1 year	at 21 days, 6 months and 1 year after each vaccination