Intradermal Trivalent Influenza Vaccine With Imiquimod

NCT01508884 | Completed

• 1 other identifier: HKU-2012-432
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the WHO International Health Regulations Emergency Committee declared an end to the 2009 H1N1 pandemic globally, the emergence of the novel 2009 H1N1 virus in March 2009 has affected more than 214 countries with at least 18000 deaths \[1\]. Patients with chronic underlying illness and extreme of ages are at risk of developing severe disease and complications \[2-3\]. Resistance to oseltamivir has also been reported \[4\]. Therefore, vaccination with the 2010/2011 trivalent influenza vaccine (TIV) with the 2009 H1N1-like virus incorporated will be the best protection against the influenza infection, especially among the at risk population. Recent study on dose sparing seasonal influenza vaccine delivered via a novel intradermal microneedle has demonstrated good immunogenic responses similar to full-dose intramuscular vaccination \[6\]. Poor immunogenicity of the H1N1 2009 component of the trivalent influenza has been reported \[7\]. Study has also suggested the combined intradermal vaccination with local stimulation of dermal antigen presenting cells by applying imiquimod cream (Aldara) to the injection site, which activate antigen presenting cells (APC) through the toll-like receptor 7 (TLR7) may produce better immunogenicity \[8\]. Imiquimod cream is currently registered for the treatment of warts and basal cell carcinoma. Scientific evidence has demonstrated that after treatment with imiquimod, the antigen is processed and presented to cells of the adaptive immune system leading to clearance of the virus and subsequent clearance of the lesions \[9\]. In addition to functional maturation, imiquimod induces migration of dendritic cells from the dermis to draining lymph nodes \[10,11\]. Subcutaneous administration of imiquimod as vaccine adjuvant simultaneously with the antigen of interest, has shown to induce enhanced responses towards the administered antigen \[12\]. We therefore performed a prospective, double blind, randomized controlled study to compare the safety and immunogenicity between intradermal 2011/2012 TIV immunization with pretreatment of imiquimod cream and conventional full dose intramuscular 2011/2012 TIV immunization with pretreatment of aqueous cream as control.

Conditions

Chronic Illness

Keywords

intradermal; influenza; vaccination

Outcome Measures

Primary Outcomes (1)

• Seroconversion rate

  The percentage of subjects with an hemagglutination inhibition antibody titre \<10 at baseline and a post-vaccination titre of ≥40 or a titre \>10 at baseline and at least a four-fold increase in titre post-vaccination on day 7

  day 7

Secondary Outcomes (15)

• Geometric mean titer old increase in influenza antibody titer

  day 21

• Seroprotection rate

  day 21

• Adverse events (Immediate)

  30 minutes after vaccination

• Geometric mean titer old increase in influenza antibody titer

  day 7

• Seroprotection rate

  day 7

Study Arms (3)

IM vaccine and placebo cream

ACTIVE COMPARATOR

A single dose of intramuscular influenza vaccine (15ug non-adjuvanted 2011/2012 TIV) with pre-treatment of the injected skin with aqueous cream

Biological: influenza vaccine; Drug: Aqueous cream

ID vaccine and placebo cream

ACTIVE COMPARATOR

A single dose of intradermal influenza vaccine (15ug non-adjuvanted 2011/2012 TIV) with pre-treatment of the injected skin with aqueous cream

Biological: influenza vaccine; Drug: Aqueous cream

ID vaccine and imiquimod cream

EXPERIMENTAL

A single dose intradermal influenza vaccine (15ug non-adjuvanted 2011/2012 TIV) with pre-treatment of the injected skin with imiquimod cream applied to the skin before vaccination

Biological: influenza vaccine; Drug: Imiquimod

Interventions

influenza vaccine BIOLOGICAL

single dose of intradermal 15 mcg non-adjuvanted 2011/2012 trivalent influenza vaccine

Also known as: Intanza 15

ID vaccine and imiquimod cream

Imiquimod DRUG

pretreatment with topical imiquimod cream to the injection site before vaccination

Also known as: Aldara

ID vaccine and imiquimod cream

Aqueous cream DRUG

pretreatment with topical aqueous cream to the injection site before vaccination

ID vaccine and placebo cream

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult patients at the age of 21 or above with chronic illness 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.

You may not qualify if:

• 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 2011/2012 TIV
• 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) infection, acute hepatitis B or C infection, autoimmune hepatitis and related 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Chronic Disease; Influenza, Human

Interventions

Influenza Vaccines; Imiquimod; vaxigrip

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ivan FN Hung, MD FRCP

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: January 9, 2012
• First Posted: January 12, 2012
• Study Start: January 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

HK (1)