Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00436046
• Collaborator: (none)
• Enrollment: 95
• Location: 1
• Arms: 3
• Duration (Months): 7
• Patients Per Site Per Month: 13.5

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Influenza	Biological: Trivalent inactivated influenza virus vaccine (2006-2007 formulation); Biological: Type 1 interferon	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Type 1 Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Apr 1, 2007
• Actual Study Completion Date: Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. [14 days after immunization.]

   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

2. Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization [28 days after immunization.]

   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

1. Local and/or Systemic Solicited Symptoms After Intranasal Immunization. [0-7 days following immunization]

   Number of participants (frequency) reporting solicited (systematically collected on a Memory Aid) reactogenicity events of any severity and number reporting severe occurrences.

2. Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. [14 days after immunization.]

   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.

3. Unsolicited Adverse Events After Intranasal Immunization [Non-serious AEs are collected through 28 days after vaccination. Serious AEs are collected through 180 days after vaccination.]

   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.

4. Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization. [28 days after immunization]

   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.

Other Outcome Measures

1. Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 14 Days After Intranasal Immunization. [14 days after immunization]

   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.

2. Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 28 Days After Intranasal Immunization. [28 days after immunization]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00436046
• Other Study ID Numbers: 06-0074; N01AI30039C
• First Posted: Feb 16, 2007
• Last Update Posted: Jun 13, 2011
• Last Verified: Oct 1, 2009

• Keywords provided by , ,: interferon, vaccine, influenza
• Additional relevant MeSH terms: Influenza, Human; Interferons

Study Results

Participant Flow

Recruitment Details	Healthy ambulatory adults were recruited from the surrounding community of the research clinic from March 16, 2007 through March 21, 2007.

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Period Title: Overall Study
STARTED	32	32	31
COMPLETED	32	32	31
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN	Total
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].	Total of all reporting groups
Overall Participants	32	32	31	95
Age (Count of Participants)
<=18 years	0 0%	1 3.1%	0 0%	1 1.1%
Between 18 and 65 years	32 100%	31 96.9%	31 100%	94 98.9%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.3 (5.2)	25.2 (4.8)	24.7 (4.9)	25.1 (4.9)
Sex: Female, Male (Count of Participants)
Female	22 68.8%	18 56.3%	23 74.2%	63 66.3%
Male	10 31.3%	14 43.8%	8 25.8%	32 33.7%
Region of Enrollment (participants) [Number]
United States	32 100%	32 100%	31 100%	95 100%

Outcome Measures

1. Primary Outcome

Title	Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization.
Description	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
Time Frame	14 days after immunization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
IgG to A/New Caledonia/20/99 at Day 14	3 9.4%	3 9.4%	5 16.1%
IgA to A/New Caledonia/20/99 at Day 14	0 0%	2 6.3%	1 3.2%
IgG to A/Wisconsin/67/2005 at Day 14	2 6.3%	3 9.4%	4 12.9%
IgA to A/Wisconsin/67/2005 at Day 14	3 9.4%	1 3.1%	6 19.4%

2. Secondary Outcome

Title	Local and/or Systemic Solicited Symptoms After Intranasal Immunization.
Description	Number of participants (frequency) reporting solicited (systematically collected on a Memory Aid) reactogenicity events of any severity and number reporting severe occurrences.
Time Frame	0-7 days following immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
Elevated Oral Temperature - Any severity	0 0%	1 3.1%	0 0%
Elevated Oral Temperature - Severe	0 0%	0 0%	0 0%
Feverishness - Any severity	0 0%	1 3.1%	2 6.5%
Feverishness - Severe	0 0%	1 3.1%	0 0%
Malaise - Any severity	7 21.9%	11 34.4%	9 29%
Malaise - Severe	0 0%	1 3.1%	2 6.5%
Myalgia - Any severity	7 21.9%	5 15.6%	5 16.1%
Myalgia - Severe	0 0%	1 3.1%	0 0%
Headache - Any severity	14 43.8%	17 53.1%	12 38.7%
Headache - Severe	0 0%	0 0%	1 3.2%
Nausea - Any severity	1 3.1%	1 3.1%	6 19.4%
Nausea - Severe	0 0%	1 3.1%	0 0%
Nasal Obstruction - Any severity	9 28.1%	10 31.3%	9 29%
Nasal Obstruction - Severe	0 0%	0 0%	0 0%
Nasal Discharge - Any severity	14 43.8%	14 43.8%	10 32.3%
Nasal Discharge - Severe	0 0%	0 0%	0 0%
Sneezing - Any severity	10 31.3%	13 40.6%	9 29%
Sneezing - Severe	0 0%	0 0%	0 0%
Sore Throat - Any severity	10 31.3%	10 31.3%	11 35.5%
Sore Throat - Severe	0 0%	0 0%	0 0%
Cough - Any severity	5 15.6%	5 15.6%	8 25.8%
Cough - Severe	0 0%	0 0%	0 0%
Any systemic symptom of any severity	21 65.6%	21 65.6%	20 64.5%
Severe systemic symptom	0 0%	1 3.1%	2 6.5%
Any local symptom of any severity	22 68.8%	24 75%	20 64.5%
Severe local symptom	0 0%	0 0%	0 0%
Any symptom of any severity	27 84.4%	28 87.5%	26 83.9%
Severe symptom	0 0%	1 3.1%	2 6.5%

3. Secondary Outcome

Title	Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization.
Description	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.
Time Frame	14 days after immunization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
HAI - A/New Caledonia/20/99 at Day 14	13 40.6%	16 50%	11 35.5%
HAI - A/Wisconsin/67/2005 at Day 14	12 37.5%	21 65.6%	7 22.6%
Neutralization - A/New Caledonia/20/99 at Day 14	12 37.5%	13 40.6%	9 29%
Neutralization - A/Wisconsin/67/2005 at Day 14	13 40.6%	16 50%	10 32.3%

4. Secondary Outcome

Title	Unsolicited Adverse Events After Intranasal Immunization
Description	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.
Time Frame	Non-serious AEs are collected through 28 days after vaccination. Serious AEs are collected through 180 days after vaccination.

Outcome Measure Data

Analysis Population Description

A reporting threshold of 5.6% was selected after reviewing adverse event rates in healthy adult volunteers in similar studies sponsored by NIAID. We determined 5.6% to be the upper bound of the confidence interval to exclude reporting events that occur in 75% of healthy adults.

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
Abdominal pain upper - Any severity	2 6.3%	0 0%	0 0%
Abdominal pain upper - Severe	0 0%	0 0%	0 0%
Upper respiratory tract infection - Any severity	4 12.5%	3 9.4%	3 9.7%
Upper respiratory tract infection - Severe	0 0%	1 3.1%	0 0%
Dysgeusia - Any severity	2 6.3%	1 3.1%	0 0%
Dysgeusia - Severe	0 0%	0 0%	0 0%
Pharyngolaryngeal pain - Any severity	1 3.1%	2 6.3%	1 3.2%
Pharyngolaryngeal pain - Severe	0 0%	0 0%	0 0%
Rhinorrhoea - Any severity	3 9.4%	0 0%	1 3.2%
Rhinorrhoea - Severe	0 0%	0 0%	0 0%
Dizziness - Any severity	2 6.3%	0 0%	0 0%
Dizziness - Severe	0 0%	0 0%	0 0%
Dysphonia - Any severity	0 0%	0 0%	2 6.5%
Dysphonia - Severe	0 0%	0 0%	0 0%
Postnasal drip - Any severity	0 0%	0 0%	2 6.5%
Postnasal drip - Severe	0 0%	0 0%	0 0%
Diarrhoea - Any severity	0 0%	3 9.4%	0 0%
Diarrhoea - Severe	0 0%	0 0%	0 0%

5. Other Pre-specified Outcome

Title	Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 14 Days After Intranasal Immunization.
Description	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.
Time Frame	14 days after immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
HAI - B/Malaysia/2506/2004 at Day 14	11 34.4%	13 40.6%	8 25.8%
Neutralization - B/Malaysia/2506/2004 at Day 14	9 28.1%	12 37.5%	8 25.8%

6. Primary Outcome

Title	Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization
Description	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.
Time Frame	28 days after immunization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
IgG to A/New Caledonia/20/99 at Day 28	1 3.1%	3 9.4%	3 9.7%
IgA to A/New Caledonia/20/99 at Day 28	1 3.1%	3 9.4%	1 3.2%
IgG to A/Wisconsin/67/2005 at Day 28	3 9.4%	4 12.5%	6 19.4%
IgA to A/Wisconsin/67/2005 at Day 28	3 9.4%	3 9.4%	4 12.9%

7. Secondary Outcome

Title	Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization.
Description	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.
Time Frame	28 days after immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
HAI - A/New Caledonia/20/99 at Day 28	14 43.8%	17 53.1%	11 35.5%
HAI - A/Wisconsin/67/2005 at Day 28	20 62.5%	23 71.9%	7 22.6%
Neutralization - A/New Caledonia/20/99 at Day 28	15 46.9%	17 53.1%	10 32.3%
Neutralization - A/Wisconsin/67/2005 at Day 28	13 40.6%	17 53.1%	8 25.8%

8. Other Pre-specified Outcome

Title	Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 28 Days After Intranasal Immunization.
Description	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.
Time Frame	28 days after immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVV With 1M IFN	IVV Without IFN	IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].	IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).	IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
Measure Participants	32	32	31
HAI - B/Malaysia/2506/2004 at Day 28	16 50%	14 43.8%	9 29%
Neutralization - B/Malaysia/2506/2004 at Day 28	13 40.6%	16 50%	13 41.9%

Adverse Events

Time Frame	Subjects recorded solicited symptoms on a memory aid for 8 days (Day 0-7)following vaccination. Unsolicited non-serious adverse events were collected for 28 days after vaccination and serious adverse events were collected through Day 180
Adverse Event Reporting Description	The occurrence of a solicited symptom on any day(s) at any severity within the 8 day (Day 0-7) period was considered one event.
Arm/Group Title	IVV With 1M IFN		IVV Without IFN		IVV With 10M IFN
Arm/Group Description	IVV (inactivated influenza virus vaccine) plus 1 Molar unit of IFN (Interferon): 0.6ml of the mixture will be given [0.5 ml of vaccine plus 0.1 ml (1 Molar unit) of IFN].		IVV only: 0.6 ml of IVV alone (0.5 ml of vaccine plus 0.1 ml of saline).		IVV plus 10 Molar units of IFN: 0.7 ml of the mixture will be given [0.5 ml of vaccine plus 0.2 ml (10 Molar units) of IFN].
All Cause Mortality
	IVV With 1M IFN		IVV Without IFN		IVV With 10M IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IVV With 1M IFN		IVV Without IFN		IVV With 10M IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	IVV With 1M IFN		IVV Without IFN		IVV With 10M IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/32 (90.6%)		29/32 (90.6%)		26/31 (83.9%)
Gastrointestinal disorders
Abdominal pain upper	2/32 (6.3%)	2	0/32 (0%)	0	0/31 (0%)	0
Diarrhoea	0/32 (0%)	0	3/32 (9.4%)	3	0/31 (0%)	0
Nausea	1/32 (3.1%)	1	1/32 (3.1%)	1	6/31 (19.4%)	6
General disorders
Feeling hot	0/32 (0%)	0	1/32 (3.1%)	1	2/31 (6.5%)	2
Malaise	7/32 (21.9%)	7	11/32 (34.4%)	11	9/31 (29%)	9
Infections and infestations
Upper respiratory tract infection	4/32 (12.5%)	4	3/32 (9.4%)	3	3/31 (9.7%)	3
Musculoskeletal and connective tissue disorders
Myalgia	7/32 (21.9%)	7	5/32 (15.6%)	5	5/31 (16.1%)	5
Nervous system disorders
Dizziness	2/32 (6.3%)	2	0/32 (0%)	0	0/31 (0%)	0
Dysgeusia	2/32 (6.3%)	2	1/32 (3.1%)	1	0/31 (0%)	0
Headache	14/32 (43.8%)	14	17/32 (53.1%)	17	12/31 (38.7%)	12
Respiratory, thoracic and mediastinal disorders
Dysphonia	0/32 (0%)	0	0/32 (0%)	0	2/31 (6.5%)	2
Pharyngolaryngeal pain	1/32 (3.1%)	1	2/32 (6.3%)	2	1/31 (3.2%)	1
Postnasal drip	0/32 (0%)	0	0/32 (0%)	0	2/31 (6.5%)	2
Rhinorrhoea	3/32 (9.4%)	3	0/32 (0%)	0	1/31 (3.2%)	1
Cough	5/32 (15.6%)	5	5/32 (15.6%)	5	8/31 (25.8%)	8
Rhinorrhoea	14/32 (43.8%)	14	14/32 (43.8%)	14	10/31 (32.3%)	10
Nasal congestion	9/32 (28.1%)	9	10/32 (31.3%)	10	9/31 (29%)	9
Sneezing	10/32 (31.3%)	10	13/32 (40.6%)	13	9/31 (29%)	9
Pharyngolaryngeal pain	10/32 (31.3%)	10	10/32 (31.3%)	10	11/31 (35.5%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.