Imiquimod and Influenza Vaccine for Immunocompromised Patients

Study Overview
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Brief Summary
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In this open label, single centre, pilot randomized controlled clinical trial the investigators aim to compare the immunogenicity and safety of a new influenza vaccination strategy consisting in the topical administration of imiquimod at the injection site before vaccination vs. a standard intramuscular vaccine injection in SOT recipients and HIV-infected individuals. The investigators planned to enroll 70 outpatients patients (50% solid-organ transplant recipients and 50% HIV-infected patients) regularly followed at the Transplantation center and the Infectious disease outpatients' clinics of the Lausanne University Hospital. Study participants will be randomized in a 1:1:1 ratio to receive the standard intramuscular vaccine (control group) or a topical application of an imiquimod containing cream followed by intramuscular (imiquimod-IM) or intradermal (imiquimod-ID) vaccine injection. After vaccination participants will be followed for a period of 180 days. Blood samples will be drawn at baseline and at day 21 and 180 for assessment of immunogenicity. Safety outcomes will be assessed immediately after vaccine administration, and at day 7 (phone call), 21 and 180.

Official Title
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Safety and Immunogenicity of Seasonal Influenza Vaccine With Topical Imiquimod in Immunocompromised Patients: A Randomized Controlled Pilot Trial

Conditions
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Influenza Vaccine

Intervention / Treatment
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* Biological: Intanza
* Biological: Mutagrip
* Drug: Aldara


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written, informed consent Age > 18 years HIV infection or at least 3 months after kidney transplantation Stable outpatients Able and willing to comply with the study protocol Exclusion Criteria: Documented egg and/or imiquimod allergy Previous life-threatening reaction to seasonal influenza vaccine (i.e. Guillain-Barré Syndrome) Previous severe reaction to imiquimod cream Pregnancy or breast-feeding Patients with autoimmune diseases For HIV-infected patients: Current active opportunistic infection For kidney transplant recipients: Ongoing therapy for rejection (including steroid pulse or prednisone > 2 mg/kg/day over more than 14 days) Ongoing therapy with IVIG and eculizumab or current and past (<6months) therapy with rituximab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intramuscular vaccine<br>The control intervention consists in the administration of the standard intramuscular influenza vaccine (Mutagrip®), containing 15 μg of each of the three viral strains without imiquimod. | Biological: Mutagrip<br> <br> |
| Experimental: Imiquimod and intradermal vaccine<br>In the imiquimod and intradermal vaccine arm, intervention consists in the topical application of a single bag of Aldara™ creme 5%, containing 12.5 mg of imiquimod, on a 16 cm2 square delimitated area on the non-dominant arm at the time of influenza vaccination. An intradermal influenza vaccine preparations containing 15 μg of each of the three viral strains (Intanza®) will be administrated in the centre of the marked area after the imiquimod cream is fully absorbed. | Biological: Intanza<br> <br> Drug: Aldara<br> <br> |
| Experimental: Imiquimod and intramuscular vaccine<br>In the imiquimod and intramuscular vaccine arm, intervention consists in the topical application of a single bag of Aldara™ creme 5%, containing 12.5 mg of imiquimod, on a 16 cm2 square delimitated area on the non-dominant arm at the time of influenza vaccination. An intramuscular influenza vaccine preparations containing 15 μg of each of the three viral strains (Mutagrip®) will be administrated in the centre of the marked area after the imiquimod cream is fully absorbed. | Biological: Mutagrip<br> <br> Drug: Aldara<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to the vaccine | Vaccine response rate (=seroconversion rate) at day 21 is the proportion of participants exhibiting a fourfold or greater increase of anti haemagglutinin (anti-HA) antibodies from baseline, measured by haemagglutinin inhibition (HI) assay 21 days after vaccination, for at least one viral strain. | 21 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rates | Seroprotection rates for each vaccine strain at baseline, and 21 and 180 days after vaccination. Seroprotection rate is defined as the proportion of patients exhibiting an anti-HA antibody titer of 1:32 or greater. | Baseline, 21 and 180 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza vaccine, Transplantation, imiquimod, HIV infection, immunogenicity