Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00436046
First received: February 15, 2007
Last updated: June 9, 2011
Last verified: October 2009
  Purpose

Influenza is a virus infection that causes sickness from the nose to the lungs. It is thought that type 1 interferon (a protein that helps the immune system fight viruses) will make flu vaccines more effective. This study will determine if type 1 interferon added to a specific flu vaccine will help the immune system of healthy adults fight off infection better than vaccine alone. Ninety volunteers, ages 18-40, will participate in this study. They will attend 3 study visits and have a final follow-up study visit, email, or phone call about six months after the vaccination. Volunteers will receive a single dose of study vaccine sprayed into the nose. Study procedures including blood samples and nasal washes (the inside of the nose is washed out) will be collected to evaluate immune system responses.


Condition Intervention Phase
Influenza
Biological: Trivalent inactivated influenza virus vaccine (2006-2007 formulation)
Biological: Type 1 interferon
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Type 1 Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. [ Time Frame: 14 days after immunization. ] [ Designated as safety issue: No ]
    Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at day 14 after immunization, relative to pre-immunization levels

  • Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization [ Time Frame: 28 days after immunization. ] [ Designated as safety issue: No ]
    Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at day 28 after immunization, relative to pre-immunization levels.


Secondary Outcome Measures:
  • Local and/or Systemic Solicited Symptoms After Intranasal Immunization. [ Time Frame: 0-7 days following immunization ] [ Designated as safety issue: Yes ]
    Number of participants (frequency) reporting solicited (systematically collected on a Memory Aid) reactogenicity events of any severity and number reporting severe occurrences.

  • Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. [ Time Frame: 14 days after immunization. ] [ Designated as safety issue: No ]
    Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 14 days after immunization, relative to pre-immunization levels.

  • Unsolicited Adverse Events After Intranasal Immunization [ Time Frame: Non-serious AEs are collected through 28 days after vaccination. Serious AEs are collected through 180 days after vaccination. ] [ Designated as safety issue: Yes ]
    Number of subjects (frequency) with spontaneous reports of Adverse Events of any severity and severe or higher severity, during the 28 days after vaccination regardless of relatedness. Events reported by more than 5.6% of subjects in any group are reported by MedDRA Preferred Term.

  • Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization. [ Time Frame: 28 days after immunization ] [ Designated as safety issue: No ]
    Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 28 days after immunization, relative to pre-immunization levels.


Enrollment: 95
Study Start Date: March 2007
Study Completion Date: October 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: 0.6 ml of IVV
30 subjects to receive 0.6 ml of inactivated influenza virus vaccine (IVV).
Biological: Trivalent inactivated influenza virus vaccine (2006-2007 formulation)
Commercially available trivalent inactivated influenza virus vaccine without or with 1 of 2 dosages of commercially available type 1 interferon administered once by nasal instillation. Dosages: 0.6 ml of IVV or 0.7 ml of IVV.
Experimental: Group 3: 0.7 ml of IVV + 10M units of IFN
30 subjects to receive 0.7 ml of IVV containing 10M units of interferon (IFN).
Biological: Trivalent inactivated influenza virus vaccine (2006-2007 formulation)
Commercially available trivalent inactivated influenza virus vaccine without or with 1 of 2 dosages of commercially available type 1 interferon administered once by nasal instillation. Dosages: 0.6 ml of IVV or 0.7 ml of IVV.
Biological: Type 1 interferon
Commercially available lyophilized IFN; dosages 1 M unit (Mu) of IFN; 10 M units (Mu) of IFN.
Experimental: Group 2: 0.6 ml of IVV + 1M unit of IFN
30 subjects to receive 0.6 ml of IVV containing 1M units of interferon (IFN).
Biological: Trivalent inactivated influenza virus vaccine (2006-2007 formulation)
Commercially available trivalent inactivated influenza virus vaccine without or with 1 of 2 dosages of commercially available type 1 interferon administered once by nasal instillation. Dosages: 0.6 ml of IVV or 0.7 ml of IVV.
Biological: Type 1 interferon
Commercially available lyophilized IFN; dosages 1 M unit (Mu) of IFN; 10 M units (Mu) of IFN.

Detailed Description:

Influenza is primarily a virus infection of the respiratory tract mucosa from the nose to the terminal bronchioles. Immunity to influenza virus infection is mediated primarily by antibody in respiratory secretions at the mucosal surface. To meet the need for improved inactivated vaccines, one potential approach is to increase the frequency and magnitude of antibody in secretions by administering inactivated influenza virus vaccine (IVV) intranasally and to optimize responses by including a mucosal adjuvant. The primary hypothesis of this study is that Type 1 interferon (IFN) will provide an adjuvant effect at the respiratory mucosal surface for production of IgA and/or IgG antibody to the influenza strains when added to IVV and administered intranasally. The primary objective of the study is to determine whether including type 1 IFN with IVV, administered intranasally, to healthy adults will enhance antibody responses in nasal secretions compared to intranasal administration of IVV alone. This is a single-center, randomized, double-blind, clinical trial to determine if type 1 IFN will act as a mucosal adjuvant for antibody responses to influenza viruses after administration with IVV intranasally. Subjects will be healthy adults between the ages of 18 and 40. The study will enroll 30 subjects in each of three groups, a group given 0.6 ml of IVV, a group given 0.6 ml of IVV containing 1M units of IFN and a group given 0.7 ml of IVV containing 10M units of IFN. The vaccine or vaccine/interferon combination will be administered to the subjects intranasally once. Blood and nasal secretions will be obtained before vaccination and again two and four weeks after immunization. Each subject will be asked to complete a memory aid for seven days and to report any unexpected adverse events (AEs) to study personnel. The subject will report to the clinic or be contacted by phone or e-mail at six months after vaccination regarding occurrence of any unreported serious adverse events (SAEs). The three nasal secretions will be used for testing for IgA and IgG antibody to the A/H1N1 and A/H3N2 HA in enzyme-linked immunosorbent assay (ELISA) tests. The three blood samples will be tested in HAI and neutralization tests for antibody to the A/H1N1 and A/H3N2 vaccine antigens.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or non-pregnant female (as indicated by a negative urine pregnancy test immediately prior to vaccine administration) between the ages of 18 and 40 years.
  • Women of childbearing potential who are at risk of becoming pregnant must agree to practice adequate contraception (e.g., barrier method, abstinence, and licensed hormonal methods) for at least 3 months after immunization.
  • Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature), medical history and a targeted physical examination based on medical history.
  • Able to understand and comply with planned study procedures.
  • Provides informed consent prior to any study procedures and is available for all study visits.

Exclusion Criteria:

  • Has a known allergy to eggs, chicken protein or other components of the vaccine.
  • Has a positive urine pregnancy test prior to vaccination (if female of childbearing potential), is lactating, or has the intention to become pregnant within 3 months of receipt of vaccine.
  • Is undergoing immunosuppression as a result of an underlying illness or treatment.
  • Has an active neoplastic disease or a history of any hematologic malignancy.
  • Is using oral or parenteral steroids or other immunosuppressive or cytotoxic drugs.
  • Has used any nasal or aerosol treatments in the past 2 weeks or likely to use any in the next 2 weeks.
  • Has a diagnosis of hay fever or asthma.
  • Has a history of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study.
  • Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric diagnosis.
  • Has received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
  • Has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses (this includes, but is not limited to: known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients).
  • Has a history of severe reactions following immunization with contemporary influenza virus vaccines.
  • Has an acute illness, including an oral temperature greater than 100.4 degrees F, within 1 week prior to vaccination.
  • Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in the study, or expects to receive an experimental agent during the 6-month study period.
  • Is planning to enroll in another clinical trial at any time during the study period.
  • Has known active human immunodeficiency virus, hepatitis B or hepatitis C infection.
  • Has a history of alcohol or drug abuse in the last 5 years.
  • Has a history of Guillain-Barre syndrome.
  • Has received the 2006-2007 formulation influenza vaccine by injection or by nose drops (fall of 2006 or since).
  • Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436046

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Director, ORA, HHS/NIAID/DMID
ClinicalTrials.gov Identifier: NCT00436046     History of Changes
Other Study ID Numbers: 06-0074, N01AI30039C
Study First Received: February 15, 2007
Results First Received: October 9, 2008
Last Updated: June 9, 2011
Health Authority: United States: Institutional Review Board
United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
interferon, vaccine, influenza

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Interferons
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 15, 2014