Enhancing Influenza Vaccination in Seniors With TLR (Toll Like Receptor) Agonists

NCT01737580 | Completed Phase 1 DMC

• 1 other identifier: H12-02574
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

The application of the TLR7/8 (Toll Like Receptor) agonist gel (immune response helper) resiquimod will enhance the immune response to the intradermal influenza vaccine in seniors 65-75 years of age.

Conditions

Influenza Vaccination in Seniors

Keywords

influenza, human; influenza vaccines; older adults; immune response

Outcome Measures

Primary Outcomes (3)

• Reactogenicity of the vaccine regimens

  Reactogenicity of the vaccine regimens (Intanza+resiquimod gel; Intanza+placebo gel) will be collected from Day 0 (pre vaccination) to Day 7. The change from Day 0 to Day 7 will be measured. The following information will be collected and compared 1) local pain (none, mild, moderate, severe; 2) injection site redness, swelling, induration measured in millimeters; itchiness present or not 3) bruising; 4) fever-values greater than or equal to 38.0 will be considered fever; 5) general symptoms-shivering, sweating nausea, vomiting diarrhea will be measured for presence or absence; 6) general symptoms-myalgia (muscle aches), arthralgia (joint aches), malaise (feeling unwell), tiredness/fatigue, headache and sleep disturbance will be measured as mild, moderate or severe

  Day 0 - Day 28

• HAI (hemagglutination inhibition)titres

  The primary immunologic outcome will be the 28 day post vaccination immune (HAI, hemagglutination immune assay titer)responses to the 3 vaccine strains present in each vaccine, assessed by the EMEA/CHMP (European Medicines Evaluation/Committee on Human Medicinal Products) Agency criteria for evaluation on immune response to influenza vaccines in persons over 60 years of age. The measurements include seroconversion rate (CHMP threshold greater than 30%), geometric mean titre (GMT) fold-increase or ratio (threshold greater than 2) and seroprotection rate (threshold greater than 60%). Whether the CHMP threshold for each measurement is met or exceeded per strain will be noted between products as descriptive information.

  Day 28 post vaccination

• Granzyme B levels and Interferon gamma to interleukin 10 ratios

  The day 0 (pre vaccination) and day 28 Granzyme B levels and Interferon gamma to interleukin 10 ratios will be measured and the change in levels from Day 0 to Day 28 will be compared in the 2 groups: 1) Intanza+resiquimod gel; 2) Intanza+placebo gel

  Day 0 and Day 28 post vaccination

Secondary Outcomes (2)

• Change in Microneutralization titres

  Day 0 and Day 28 post vaccination

• baseline Granzyme B Activity

  Day 0 and Day 28 post vaccination

Study Arms (2)

Intanza+resiquimod gel

ACTIVE COMPARATOR

Intanza 15mcg intradermal injection + resiquimod gel applied to the vaccination site immediately post vaccination.

Drug: resiquimod

Intanza + placebo gel

PLACEBO COMPARATOR

Intanza 15mcg intradermal injection + placebo gel applied to the vaccination site immediately post vaccination.

Drug: placebo gel

Interventions

resiquimod DRUG

Also known as: R-848

Intanza+resiquimod gel

placebo gel DRUG

Intanza + placebo gel

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• written informed consent provided by the subject, who can be male or female
• subjects who the investigator believes can and will comply with the requirements of the protocol (i.e. return for follow-up visits, record safety observations and able to converse with study personnel including by personal telephone
• male or female age 65-75 years at visit 1
• in generally good health (stable chronic conditions acceptable), living independently or with minimal assistance (clinical frailty score 1-5) and able to attend clinic appointments
• receipt of influenza vaccination for the 2012-2013 influenza season

You may not qualify if:

• receipt of any live vaccine within 4 weeks or inactivated vaccine within one week of visit 1 or planned administration of any non-study vaccines between visits 1 and 2
• systemic hypersensitivity to influenza vaccine, hen's eggs or other vaccine constituent e.g. neomycin sulphate, kanamycin, formalin
• severe reaction to any previous influenza vaccine or vaccine component
• bleeding disorder, including anticoagulant therapy or thrombocytopenia, that contraindicates IM (intramuscular) injection or blood collection (does not include daily low dose ASA (acetylsalicylic acid), Plavix, and certain other mild anticoagulants with minimal bleeding risk)
• incapacity to provide fully informed consent or be attentive to follow-up observations, resulting from cognitive impairment, abuse of alcohol, or drug addiction
• lack of telephone access, inadequate fluency in English, uncertain availability during the 4 week study participation
• immune compromise resulting from disease or immunosuppressive systemic medication use within 3 months of visit 1
• receipt of blood or blood products within 3 months of visit 1
• unstable medical conditions, as indicated by a requirement for hospitalization or a substantial medication change to stabilize said condition within 3 months.
• personal frailty, determined by Clinical Frailty score of 6-7 (moderately frail or severely frail)or failure on the TUG test (Timed Up and Go time greater than 10 seconds) or inability to walk 1/4 mile, based on self report
• history of Guillain-Barre Syndrome
• psoriasis
• recent or current febrile illness with oral temperature greater or equal to 38.0 degrees centigrade or other moderate to severe illness within the previous 48 hours (may vaccinate once condition has resolved)

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

resiquimod

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Jan P Dutz, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: November 29, 2012
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 28, 2013

Record last verified: 2013-08

Locations

CA (1)