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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04143451
Recruitment Status : Recruiting
First Posted : October 29, 2019
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Dr Ivan FN Hung, The University of Hong Kong

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

Condition or disease Intervention/treatment Phase
Influenza Biological: Vaxigrip tetra Biological: Fluzone high-dose Drug: Aldara 5% Topical Cream Drug: Aqueous cream BP Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4000 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double blind randomised controlled trial
Masking: Double (Participant, Investigator)
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.
Primary Purpose: Prevention
Official Title: Intradermal Quadrivalent Influenza Vaccine With Topical Imiquimod in Elderly & Chronic Ill Subjects, a Double-Blind Randomized Controlled Trial
Actual Study Start Date : October 23, 2019
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Active Comparator: IQ

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.

Biological: Vaxigrip tetra
quadrivalent influenza vaccine

Drug: Aldara 5% Topical Cream
imiquimod cream

Active Comparator: IM

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.

Biological: Vaxigrip tetra
quadrivalent influenza vaccine

Drug: Aqueous cream BP
inactive aqueous cream

Active Comparator: HD

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.

Biological: Fluzone high-dose
high-dose trivalent influenza vaccine

Drug: Aqueous cream BP
inactive aqueous cream




Primary Outcome Measures :
  1. Mortality [ Time Frame: 3 years ]
    death rate

  2. Overall hospitalisation [ Time Frame: 3 years ]
    hospitalisation rate for all diagnosis

  3. Hospitalisation for influenza [ Time Frame: 3 years ]
    hospitalisation rate with microbiological confirmation of influenza

  4. Hospitalisation for pneumonia [ Time Frame: 3 years ]
    hospitalisation rate with a clinical diagnosis of pneumonia


Secondary Outcome Measures :
  1. immediate adverse events [ Time Frame: 5 minutes post vaccination ]
    immediate adverse events

  2. adverse events [ Time Frame: 7 days post vaccination ]
    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.

  3. immunogenicity [ Time Frame: at 21 days, 6 months and 1 year after each vaccination ]
    GMT, seroconversion rate, seroprotection rate and GMT fold increase by HI and MN assays on day, 21, 6 months and 1 year



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04143451


Contacts
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Contact: Ivan FN Hung, MD FRCP 22554049 ivanhung@hku.hk
Contact: Kelvin To, MD FRCPath 22553111 kelvinto@hku.hk

Locations
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Hong Kong
University of Hong Kong, Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Ivan FN Hung, MD FRCP    852 22554049    ivanfn@gmail.com   
Sub-Investigator: Kelvin To, MD FRCPath         
Sub-Investigator: KY Yuen, MD FRCPath         
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong

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Responsible Party: Dr Ivan FN Hung, Professor of Medicine, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04143451    
Other Study ID Numbers: UW 17-372
First Posted: October 29, 2019    Key Record Dates
Last Update Posted: November 7, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Dr Ivan FN Hung, The University of Hong Kong:
influenza, intradermal, imiquimod, high-dose, vaccine
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Imiquimod
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers