MI-CP217: A Study to Evaluate the Safety of HIN1 Monovalent Vaccine (MEDI3414) in Children 2 to 17 Years of Age

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00946101
• Collaborator: Department of Health and Human Services (U.S. Fed)
• Enrollment: 326
• Locations: 16
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 20.4
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The purpose of this study was to determine the safety and descriptive immunogenicity of the H1N1 influenza vaccine in healthy children.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: MEDI3414 [Influenza A(H1N1) live attenuated, intranasal]; Biological: Placebo	Phase 4

Detailed Description

The primary objective of this study was to assess the safety and descriptive immunogenicity of a monovalent influenza virus vaccine containing a new 6:2 influenza virus reassortant in healthy children.

Study Design

• Study Type: Interventional
• Actual Enrollment: 326 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of MEDI3414 in Children
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MEDI3414 [Influenza A (H1N1) vaccine] MEDI3414- Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of influenza virus type A/California/07/2009.	Biological: MEDI3414 [Influenza A(H1N1) live attenuated, intranasal]; 0.5 mL: (intranasal sprayer)
Placebo Comparator: Placebo Placebo - Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer	Biological: Placebo; Placebo was supplied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C). [Days 1- 8]

   The number of participants with fever between the two treatment groups was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo). The upper limit of the two-sided 95% confidence intervals was evaluated against the prespecified equivalence criterion of 10% which corresponded to the following hypotheses: H0 (null): rate difference ≥ 10%, HA (alternative): rate difference < 10%.

2. Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [Day 1, Day 15]

   Seroresponse is described as greater than or equal to a 4-fold rise in hemagglutination inhibition (HAI) titer from baseline. All immunogenicity analyses was based on the immunogenicity population.

3. Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [Day 1, Day 29]

   Seroresponse is described as greater than or equal to a 4-fold rise in HAI titer from baseline. All immunogenicity analyses are based on the immunogenicity population.

4. Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [Day 1, Day 57]

   Seroresponse is described as greater than or equal to a 4-fold rise in HAI titer from baseline. All immunogenicity analyses are based on the immunogenicity population.

Secondary Outcome Measures

1. Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1 [Days 1-8]

   Other solicited symptoms include fever (> 100°F [37.8°C] axillary), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) or tiredness/weakness, decreased appetite.

2. Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1 [Days 1-8]

3. Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1 [Days 1-8]

4. Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1 [Days 1-15]

5. Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1 [Days 1-15]

6. Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1 [Days 1-15]

7. Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2 [Days 29-36]

8. Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2 [Days 29-36]

9. Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2 [Days 29-36]

10. Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2 [Days 29-43]

11. Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2 [Days 29-43]

12. Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2 [Days 29-43]

13. Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1. [Days 1-29]

    An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).

14. Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1 [Days 1-29]

    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.

15. Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2. [Days 29-57]

    An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).

16. Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2 [Days 29-57]

    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.

17. Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product. [Days 1-209]

    An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).

18. Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product. [Days 1-209]

    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.

19. Number of Participants Who Achieve a Post Dose 1 (Day 15) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus. [Day 1, Day 15]

    All immunogenicity analyses are based on the immunogenicity population.

20. Number of Participants Who Achieve a Post Dose 1 (Day 29) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus. [Day 1, Day 29]

    All immunogenicity analyses are based on the immunogenicity population.

21. Number of Participants Who Achieve a Post Dose 2 (Day 57) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus. [Day 1, Day 57]

    All immunogenicity analyses are based on the immunogenicity population.

22. Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15) [Day 1, Day 15]

    All immunogenicity analyses are based on the immunogenicity population.

23. Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29) [Day 1, Day 29]

    All immunogenicity analyses are based on the immunogenicity population.

24. Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57) [Day 1, Day 57]

    All immunogenicity analyses are based on the immunogenicity population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female, 2 to 17 years of age (not yet reached their 18th birthday) at the time of randomization

• Healthy by medical history and physical exam

• Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU and written informed assent) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations

• Females of child-bearing potential, (ie, unless premenarchal, surgically sterile [eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy], has sterile male partner, or practices abstinence) must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 60 days after the second dose of investigational product. In addition, the subject must also have a negative urine or blood pregnancy test at screening and, if screening and Day 1 do not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment is required to assess the childbearing potential of a pre-adolescent or adolescent girl.

• Males, unless not sexually active, must use an effective method of birth control with a female partner and must agree to continue using such contraceptive precautions for at least 30 days after the second dose of investigational product (from Day 1 through Day 59 of the study)

• Subject's legal representative available by telephone

• Subject/subject's legal representative is able to understand and comply with the requirements of the protocol, as judged by the investigator

• Ability to complete follow-up period of 180 days after Dose 2 as required by the protocol

Exclusion Criteria:

• History of hypersensitivity to any component of the investigational product including egg or egg protein, gelatin or arginine, or serious, life-threatening, or severe reactions to previous influenza vaccinations

• History of hypersensitivity to gentamicin

• Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (eg, asthma), chronic metabolic diseases (eg, diabetes mellitus), renal dysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year

• Acute febrile (> 100.0°F oral or equivalent) and/or clinically significant respiratory illness (eg, cough or sore throat) within 14 days prior to randomization

• History of asthma, or in children < 5 years of age, history of recurrent wheezing

• Any known immunosuppressive condition or immune deficiency disease, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy

• History of Guillain-Barré syndrome

• A household contact who is severely immunocompromised (eg, hematopoietic stem cell transplant recipient, during those periods in which the immunocompromised individual requires care in a protective environment); subject should additionally avoid close contact with severely immunocompromised individuals for at least 21 days after receipt of investigational product

• Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the second dose of investigational product (use of licensed agents for indications not listed in the package insert is permitted)

• Use of aspirin or salicylate-containing products within 30 days prior to randomization or expected receipt through 30 days after final vaccination

• Expected receipt of antipyretic or analgesic medication (non-salicylate-containing) on a daily or every other day basis from randomization through 14 days after receipt of each dose of investigational product

• Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of each dose of investigational product

• Receipt of any nonstudy vaccine within 30 days before or after Dose 1 or expected receipt of any nonstudy vaccine within 30 days before or after Dose 2

• Known or suspected mitochondrial encephalomyopathy

• Adolescent subject is pregnant or a nursing mother

• Any condition (eg, chronic cough, allergic rhinitis) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

• Subject, legal representative, or immediate family member of subject is an employee of the clinical study site or is otherwise in involved with the conduct of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinic Research, Inc.	Mobile	Alabama	United States	36608
2	Benchmark Research	Sacramento	California	United States	95816
3	California Research Foundation	San Diego	California	United States	92103-6204
4	Benchmark Research	San Francisco	California	United States	94102
5	Kentucky Pediatric Research Center	Bardstown	Kentucky	United States	40004
6	Central Kentucky Research Associates, Inc.	Lexington	Kentucky	United States	40509
7	Sundance Clinical Research	St. Louis	Missouri	United States	63141
8	Meridian Clinical Research	Omaha	Nebraska	United States	68134
9	Clinical Research Center of Nevada	Henderson	Nevada	United States	89105
10	Rochester Clinical Research Inc.	Rochester	New York	United States	14069
11	Primary Physicians Research, Inc.	Pittsburgh	Pennsylvania	United States	15241
12	Omega Medical Research	Warwick	Rhode Island	United States	02886
13	Spartanburg Medical Research	Spartanburg	South Carolina	United States	29303
14	Benchmark Research	Austin	Texas	United States	78705
15	Benchmark Research Ft. Worth	Ft. Worth	Texas	United States	76135
16	Benchmark Research San Angelo	San Angelo	Texas	United States	76904

Sponsors and Collaborators

• MedImmune LLC
• Department of Health and Human Services

Investigators

• Study Director: Elissa Malkin, D.O., MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00946101
• Other Study ID Numbers: MI-CP217; HHS/ASPR
• First Posted: Jul 24, 2009
• Last Update Posted: Aug 11, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: randomized, double-blind, placebo-controlled

Study Results

Participant Flow

Recruitment Details	Study participation began once written informed consent was obtained. The first and last dates of informed consent were 03 Aug 2009 and 19 Aug 2009. Once informed consent was obtained, a subject identification number was assigned using an interactive voice response system, and screening evaluations began to assess study eligibility.
Pre-assignment Detail	Eligible subjects were randomly assigned in a 4:1 ratio to receive 2 doses of study monovalent vaccine or placebo by intranasal spray; the doses were administered approximately 28 days apart, on Days 1 and 29.

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Period Title: Overall Study
STARTED	261	65
Day 15 Post Dose 1	260	64
Day 15 Post Dose 2	254	63
COMPLETED	257	63
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo	Total
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Total of all reporting groups
Overall Participants	261	65	326
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.9 (4.3)	9.2 (4.3)	9.0 (4.3)
Sex: Female, Male (Count of Participants)
Female	130 49.8%	36 55.4%	166 50.9%
Male	131 50.2%	29 44.6%	160 49.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	50 19.2%	17 26.2%	67 20.6%
Not Hispanic or Latino	211 80.8%	48 73.8%	259 79.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	4 1.5%	0 0%	4 1.2%
Asian	2 0.8%	4 6.2%	6 1.8%
Native Hawaiian or Other Pacific Islander	2 0.8%	0 0%	2 0.6%
Black or African American	43 16.5%	12 18.5%	55 16.9%
White	198 75.9%	43 66.2%	241 73.9%
More than one race	8 3.1%	1 1.5%	9 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Other	4 1.5%	5 7.7%	9 2.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C).
Description	The number of participants with fever between the two treatment groups was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo). The upper limit of the two-sided 95% confidence intervals was evaluated against the prespecified equivalence criterion of 10% which corresponded to the following hypotheses: H0 (null): rate difference ≥ 10%, HA (alternative): rate difference < 10%.
Time Frame	Days 1- 8

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	4 1.5%	1 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The rate of subjects with fever between the two treatment groups was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo). The upper limit of the two-sided 95% confidence intervals was evaluated against the pre-specified equivalence criterion of 10% which corresponds to the following hypotheses: H0 (null): rate difference ≥ 10%, HA (alternative): rate difference < 10%
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	For the calculation of the power to rule out a 10% increase of fever rate in vaccine recipients with 300 evaluable subjects (240 vaccine and 60 placebo recipients), it is assumed that the true fever rate in the monovalent vaccine group is 3.0% to 8.0%,and the true fever rate in placebo group is 0% to 3% lower than the fever rate in the vaccine group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -6.4 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse is described as greater than or equal to a 4-fold rise in hemagglutination inhibition (HAI) titer from baseline. All immunogenicity analyses was based on the immunogenicity population.
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis (H1N1=129; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	129	32
Number [participants]	10 3.8%	2 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The number of subjects who experienced a post-dose seroresponse was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -12.8 to 9.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse is described as greater than or equal to a 4-fold rise in HAI titer from baseline. All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65) and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 (H1N1=126; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	126	32
Number [participants]	14 5.4%	2 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The number of subjects who experienced a post-dose seroresponse was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; -9.6 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse is described as greater than or equal to a 4-fold rise in HAI titer from baseline. All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 57

Outcome Measure Data

Analysis Population Description

Participants who received 2 doses of the same study vaccine (H1N1=258; Placebo=65) and had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis (H1N1=250; Placebo=62).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	250	62
Number [participants]	80 30.7%	9 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The number of subjects who experienced a post-dose seroresponse was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	17.5
	Confidence Interval	(2-Sided) 95%; 5.5 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1
Description	Other solicited symptoms include fever (> 100°F [37.8°C] axillary), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) or tiredness/weakness, decreased appetite.
Time Frame	Days 1-8

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65), experienced any follow-up for safety and had solicited symptoms data available during the reporting period (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	97 37.2%	21 32.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	Rates of solicited symptoms following each dose (Days 1 to 8 and Days 1 to 15) between the two treatment groups were compated following each dose. Exact two-sided 95% confidence intervals (Chan and Zhang, 1999) on the rate difference (Vaccine minus Placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	5.1
	Confidence Interval	(2-Sided) 95%; -8.4 to 17.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1
Time Frame	Days 1-8

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	28 10.7%	7 10.8%

7. Secondary Outcome

Title	Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1
Time Frame	Days 1-8

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	18 6.9%	1 1.5%

8. Secondary Outcome

Title	Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65), experienced any follow-up for safety, and had solicited symptoms data available during the reporting period (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	122 46.7%	22 33.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	Rates of solicited symptoms following each dose (Days 1 to 8 and Days 1 to 15) between the two treatment groups were compared following each dose. Exact two-sided 95% confidence intervals (Chan and Zhang, 1999) on the rate difference (Vaccine minus Placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	13.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	47 18%	11 16.9%

10. Secondary Outcome

Title	Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	27 10.3%	2 3.1%

11. Secondary Outcome

Title	Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-36

Outcome Measure Data

Analysis Population Description

The safety population for solicited symptoms Dose 2 included all participants who received Dose 2 (H1N1=258; Placebo=65), experienced any follow-up for safety and had solicited symptom data available during the reporting period (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	65 24.9%	20 30.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	Rates of solicited symptoms following each dose (Days 1 to 8 and Days 1 to 15) between the two treatment groups were compared following each dose. Exact two-sided 95% confidence intervals (Chan and Zhang, 1999) on the rate difference (Vaccine minus Placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	-6.3
	Confidence Interval	(2-Sided) 95%; -19.7 to 6.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-36

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo) and experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	20 7.7%	2 3.1%

13. Secondary Outcome

Title	Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-36

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo=65) and experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	10 3.8%	5 7.7%

14. Secondary Outcome

Title	Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-43

Outcome Measure Data

Analysis Population Description

The safety population for solicited symptoms Dose 2 included all participants who received Dose 2 (H1N1=258; Placebo=65), experienced any follow-up for safety and had solicited symptom data available during the reporting period (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	93 35.6%	27 41.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine
	Comments	Rates of solicited symptoms following each dose (Days 1 to 8 and Days 1 to 15) between the two treatment groups were compared following each dose. Exact two-sided 95% confidence intervals (Chan and Zhang, 1999) on the rate difference (Vaccine minus Placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) 95%; -20.3 to 7.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-43

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo=65), experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	35 13.4%	9 13.8%

16. Secondary Outcome

Title	Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2
Time Frame	Days 29-43

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo=65), experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	22 8.4%	11 16.9%

17. Secondary Outcome

Title	Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1.
Description	An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).
Time Frame	Days 1-29

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1
Description	SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame	Days 1-29

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	1 0.4%	0 0%

19. Secondary Outcome

Title	Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2.
Description	An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).
Time Frame	Days 29-57

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo=65) and experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	0 0%	1 1.5%

20. Secondary Outcome

Title	Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2
Description	SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame	Days 29-57

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received Dose 2 (H1N1=258; Placebo=65) and experienced any follow-up for safety (H1N1=255; Placebo=63).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	255	63
Number [participants]	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product.
Description	An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of NOCDs included, but were not limited to, diabetes, asthma, autoimmune disease (eg, lupus, rheumatoid arthritis), and neurological disease (eg, epilepsy, autism). Examples of events not considered NOCDs were mild eczema, diagnosis of a congenital anomaly present at study entry, or acute illness (eg, otitis media, bronchitis).
Time Frame	Days 1-209

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [Participants]	0 0%	1 1.5%

22. Secondary Outcome

Title	Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product.
Description	SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame	Days 1-209

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of investigational product (H1N1=259; Placebo=65) and experienced any follow-up for safety (H1N1=259; Placebo=65).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	259	65
Number [participants]	2 0.8%	1 1.5%

23. Secondary Outcome

Title	Number of Participants Who Achieve a Post Dose 1 (Day 15) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus.
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis (H1N1=129; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	129	32
Number [participants]	13 5%	1 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine
	Comments	The number of subjects who achieved a post Dose 1 HAI titer greater than or equal to 32 against the H1N1 strain was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	7.0
	Confidence Interval	(2-Sided) 95%; -6.1 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Number of Participants Who Achieve a Post Dose 1 (Day 29) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus.
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis (H1N1=126; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	126	32
Number [participants]	13 5%	1 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The number of subjects who achieved a post Dose 1 HAI titer greater than or equal to 32 against the H1N1 strain was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 95%; -5.8 to 15.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Number of Participants Who Achieve a Post Dose 2 (Day 57) HAI Titer Greater Than or Equal to 32 Against the H1N1 Strain in All Participants, Regardless of Baseline Serostatus.
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 57

Outcome Measure Data

Analysis Population Description

Participants who received 2 doses of the same study vaccine (H1N1=258; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis (H1N1=250; Placebo=62).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	250	62
Number [participants]	66 25.3%	6 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	H1N1 Monovalent Influenza Vaccine, Placebo
	Comments	The number of subjects who achieved a post Dose 2 HAI titer greater than or equal to 32 against the H1N1 strain was compared based on the upper limit of the two-sided 95% exact confidence intervals for the rate difference (Vaccine minus Placebo).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	rate difference
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 5.9 to 25.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15)
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis (H1N1=129; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	129	32
Geometric Mean (Full Range) [titer]	3.55	2.89

27. Secondary Outcome

Title	Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29)
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

Participants who received Dose 1 of study vaccine (H1N1=259; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis (H1N1=126; Placebo=32).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	126	32
Geometric Mean (Full Range) [titer]	3.53	2.71

28. Secondary Outcome

Title	Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57)
Description	All immunogenicity analyses are based on the immunogenicity population.
Time Frame	Day 1, Day 57

Outcome Measure Data

Analysis Population Description

Participants who received 2 doses of the same study vaccine (H1N1=258; Placebo=65), had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis (H1N1=250; Placebo=62).

Arm/Group Title	H1N1 Monovalent Influenza Vaccine	Placebo
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009. Subjects were to receive two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers. Subjects were to receive a total of 2 doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
Measure Participants	250	62
Geometric Mean (Full Range) [titer]	7.61	3.70

Adverse Events

Time Frame	Adverse event data were collected through 14 days after each vaccination, ie, Days 1-15 and Days 29-43. Serious adverse events (SAEs) were collected through 28 days after each vaccination, ie, Days 1-28 and Days 29-57 and through 180 days post last dose.
Adverse Event Reporting Description	Telephone contacts were made by site personnel to the participant/participant's parent or legal guardian at various times during the study to assess safety.
Arm/Group Title	H1N1 Monovalent Vaccine Days 1-28		Placebo Days 1-28		H1N1 Monvalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent Vaccine Days 58-209		Placebo Days 58-209
Arm/Group Description	MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009.		Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers		MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009.		Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers.		MEDI3414- Monovalent vaccine supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of influenza virus type A/California/07/2009.		Placebo - 0.5 mL of sucrose-phosphate buffer contained in intranasal sprayers.
All Cause Mortality
	H1N1 Monovalent Vaccine Days 1-28		Placebo Days 1-28		H1N1 Monvalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent Vaccine Days 58-209		Placebo Days 58-209
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	H1N1 Monovalent Vaccine Days 1-28		Placebo Days 1-28		H1N1 Monvalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent Vaccine Days 58-209		Placebo Days 58-209
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/259 (0.4%)		0/65 (0%)		0/255 (0%)		0/63 (0%)		1/259 (0.4%)		1/65 (1.5%)
Infections and infestations
Cellulitis staphylococcal	0/259 (0%)	0	0/65 (0%)	0	0/255 (0%)	0	0/63 (0%)	0	0/255 (0%)	0	1/63 (1.6%)	1
Osteomyelitis	0/259 (0%)	0	0/65 (0%)	0	0/255 (0%)	0	0/63 (0%)	0	1/255 (0.4%)	1	0/63 (0%)	0
Psychiatric disorders
Depression	1/259 (0.4%)	1	0/65 (0%)	0	0/255 (0%)	0	0/63 (0%)	0	0/255 (0%)	0	0/63 (0%)	0
Other (Not Including Serious) Adverse Events
	H1N1 Monovalent Vaccine Days 1-28		Placebo Days 1-28		H1N1 Monvalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent Vaccine Days 58-209		Placebo Days 58-209
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/259 (5%)		2/65 (3.1%)		11/255 (4.3%)		3/63 (4.8%)		0/255 (0%)		0/63 (0%)
Gastrointestinal disorders
nausea	5/259 (1.9%)	6	2/65 (3.1%)	2	2/255 (0.8%)	3	1/63 (1.6%)	2	0/255 (0%)	0	0/63 (0%)	0
vomiting	7/259 (2.7%)	7	1/65 (1.5%)	1	6/255 (2.4%)	6	2/63 (3.2%)	2	0/255 (0%)	0	0/63 (0%)	0
diarrhea	4/259 (1.5%)	4	1/65 (1.5%)	1	5/255 (2%)	5	0/63 (0%)	0	0/255 (0%)	0	0/63 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.