MI-CP215: A Study to Evaluate the Safety of H1N1 Monovalent Vaccine (MEDI3414) in Healthy Adults

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00945893
• Collaborator: Department of Health and Human Services (U.S. Fed)
• Enrollment: 300
• Locations: 5
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 60
• Patients Per Site Per Month: 8.6

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 adults.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: MEDI3414 [Influenza A/H1N1 live attenuated, intranasal]; Other: 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 adults.

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 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 Adults
• 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
Experimental: MEDI3414 [Influenza A (H1N1) vaccine] MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 fluorescent focus units (FFU) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.	Biological: MEDI3414 [Influenza A/H1N1 live attenuated, intranasal]; 0.5 mL; (intranasal sprayer); Other Names: MEDI3414
Placebo Comparator: Placebo Placebo -Placebo was supplied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer.	Other: Placebo; (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 Oral 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 (CIs) for the rate difference (Vaccine minus Placebo). The upper limit of the two-sided 95% CI 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 Experienced a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [Day 1, Day 15]

   Seroresponse was defined as a ≥ 4-fold rise in hemagglutination inhibition (HAI) titer from baseline. All immunogenicity analyses were based on the immunogenicity population.

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

   Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were based on the immunogenicity population.

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

   Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were based on the immunogenicity population.

Secondary Outcome Measures

1. Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 1 [Days 1-8]

   Solicited symptoms were events considered likely to occur post dosing. For this study, other solicited symptoms included: Fever (> 100°F [37.8°C] oral), Runny nose, Sore throat, Cough, Vomiting, Muscle aches, Chills, Decreased activity (tiredness), and Headache.

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

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

4. Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 1 [Days 1-15]

5. Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 1 [Days 1-15]

6. Number of Participant Using Anti-pyretic and Analgesic Agents Within 14 Days Post Vaccination, Dose 1 [Days 1-15]

7. Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 2 [Days 29-36]

8. Number of Participants Reporting AEs Within 7 Days Post Vaccination, Dose 2 [Days 29-36]

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

10. Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 2 [Days 29-43]

11. Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 2 [Days 29-43]

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

13. Number of Participants With Serious Adverse Events (SAEs) Through 28 Days Post Vaccination, 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 birth defect 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.

14. Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days Post Vaccination, 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).

15. Number of Participants With SAEs Through 28 Days Post Vaccination, 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 birth defect 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.

16. Number of Participants With NOCDs Within 28 Days Post Vaccination, 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).

17. Number of Participants With SAEs Through 180 Days Post Final Dose [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 birth defect 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.

18. Number of Participants With NOCDs Through 180 Days Post Final Dose. [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).

19. Number of Participants Who Achieved a Post Dose 1 (Day 15) HAI Titer ≥ 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 Achieved a Post Dose 1 (Day 29) HAI Titer ≥ 32 Against the H1N1 Strain in All Subjects Regardless of Baseline Serostatus [Day 1, Day 29]

    All immunogenicity analyses are based on the immunogenicity population.

21. Number of Participants Who Achieved a Post Dose 2 (Day 57) HAI Titer ≥ 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 29) [Day 1, Day 57]

    All immunogenicity analyses are based on the immunogenicity population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female, 18 to 49 years of age (not yet reached their 50th birthday) at the time of randomization

• Healthy by medical history and physical examination

• 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) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations

• Females of childbearing potential, (ie, unless surgically sterile [eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy], has sterile male partner, is at least 1 year post menopause, 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.

• 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 is available by telephone

• Subject is able to understand and comply with the requirements of the protocol, as judged by the investigator

• Subject is able 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

• 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)

• Expected receipt of antipyretic or analgesic medication 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

• 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 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	Covance Daytona Beach	Daytona Beach	Florida	United States	30060
2	Pharmax Research Clinic	Miami	Florida	United States	33126
3	Miami Research Associates	South Miami	Florida	United States	33143
4	Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
5	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• MedImmune LLC
• Department of Health and Human Services

Investigators

• Study Director: Raburn Mallory, M.D., MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT00945893
• Other Study ID Numbers: MI-CP215; HHS/ASPR
• First Posted: Jul 24, 2009
• Last Update Posted: Sep 12, 2011
• Last Verified: Sep 1, 2011

Study Results

Participant Flow

Recruitment Details	Subjects were screened for the study within 14 days prior to randomization. The first and last dates of informed consent were 03 Aug 2009 and 18 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 monovalent vaccine or placebo by intranasal spray; the doses were administered approximately 28 days apart, on Days 1 and 29.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Period Title: Overall Study
STARTED	60	240
Day 15 Post Dose 1	60	238
Day 15 Post Dose 2	54	226
COMPLETED	57	230
NOT COMPLETED	3	10

Baseline Characteristics

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]	Total
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.	Total of all reporting groups
Overall Participants	60	240	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.1 (8.9)	33.3 (9.2)	33.5 (9.2)
Sex: Female, Male (Count of Participants)
Female	33 55%	138 57.5%	171 57%
Male	27 45%	102 42.5%	129 43%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 30%	95 39.6%	113 37.7%
Not Hispanic or Latino	42 70%	145 60.4%	187 62.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	0 0%	1 0.4%	1 0.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	1 0.3%
Black or African American	13 21.7%	37 15.4%	50 16.7%
White	47 78.3%	199 82.9%	246 82%
More than one race	0 0%	1 0.4%	1 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Other	0 0%	1 0.4%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Oral 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 (CIs) for the rate difference (Vaccine minus Placebo). The upper limit of the two-sided 95% CI 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

Safety Population was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The upper limit of the two-sided 95% CI 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%
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The currently proposed study provided at least 99.9% power to rule out a rate increase of 10 percentage points assuming the true difference between the treatment groups is zero and the true fever rate is ≤ 3%. Power is also high if the true difference is slightly greater than zero and the true fever rate is ≤ 3%.
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%; -6.0 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants Who Experienced a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse was defined as a ≥ 4-fold rise in hemagglutination inhibition (HAI) titer from baseline. All immunogenicity analyses were based on the immunogenicity population.
Time Frame	Day 1, Day 15

Outcome Measure Data

Analysis Population Description

For each treatment group, participants were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw occur on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	30	120
Number [Participants]	0 0%	3 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants who experienced a post-dose seroresponse was compared based on the upper limit of the limit of the two-sided 95% exact CI 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	2.5
	Confidence Interval	(2-Sided) 95%; -8.8 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Participants Who Experienced a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were based on the immunogenicity population.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

For each treatment group, participants were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw occur on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	29	115
Number [Participants]	0 0%	7 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants who experienced a post-dose seroresponse was compared based on the upper limit of the two-sided 95% exact CIs 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	6.1
	Confidence Interval	(2-Sided) 95%; -5.6 to 12.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Participants Who Experienced a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
Description	Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were 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 investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	54	222
Number [Participants]	3 5%	33 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants who experienced a post-dose seroresponse was compared based on the upper limit of the limit of the two-sided 95% exact CI 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	9.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 1
Description	Solicited symptoms were events considered likely to occur post dosing. For this study, other solicited symptoms included: Fever (> 100°F [37.8°C] oral), Runny nose, Sore throat, Cough, Vomiting, Muscle aches, Chills, Decreased activity (tiredness), and Headache.
Time Frame	Days 1-8

Outcome Measure Data

Analysis Population Description

The Safety population for solicited symptoms was defined as all participants who received at least one dose of investigational product, had any follow-up for safety and had solicited symptom data available during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	19 31.7%	100 41.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	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% CIs (Chan and Zhang, 1999) on the rate difference (monovalent vaccine minus placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -4.1 to 22.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	7 11.7%	26 10.8%

7. Secondary Outcome

Title	Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days Post Vaccination, Dose 1.
Time Frame	Days 1-8

Outcome Measure Data

Analysis Population Description

The Safety population was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	3 5%	20 8.3%

8. Secondary Outcome

Title	Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The Safety Population for solicited symptoms was defined as all participants who received at least one dose of investigational product, had any follow-up for safety and had solicited symptom data available during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	28 46.7%	113 47.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	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% CIs (Chan and Zhang, 1999) on the rate difference (monovalent vaccine minus placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -13.9 to 14.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	10 16.7%	38 15.8%

10. Secondary Outcome

Title	Number of Participant Using Anti-pyretic and Analgesic Agents Within 14 Days Post Vaccination, Dose 1
Time Frame	Days 1-15

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	3 5%	30 12.5%

11. Secondary Outcome

Title	Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 2
Time Frame	Days 29-36

Outcome Measure Data

Analysis Population Description

The Safety Population for solicited symptoms dose 2 was defined as all participants who received Dose 2, had any follow-up for safety and had solicited symptom data available during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	15 25%	61 25.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	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% CIs (Chan and Zhang, 1999) on the rate difference (monovalent vaccine minus placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -14.7 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants Reporting AEs Within 7 Days Post Vaccination, Dose 2
Time Frame	Days 29-36

Outcome Measure Data

Analysis Population Description

Participants in the Safety Population who received Dose 2 and had any follow-up for safety during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	3 5%	12 5%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the safety population who received Dose 2 and had any follow-up for safety during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	2 3.3%	4 1.7%

14. Secondary Outcome

Title	Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 2
Time Frame	Days 29-43

Outcome Measure Data

Analysis Population Description

Participants in the Safety Population who received Dose 2 and had solicited symptom data available during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	17 28.3%	75 31.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	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% CIs (Chan and Zhang, 1999) on the rate difference (monovalent vaccine minus placebo) were constructed. There were no prespecified equivalence criteria for the secondary analyses.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -12.6 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 2
Time Frame	Days 29-43

Outcome Measure Data

Analysis Population Description

Participants in the Safety Population who received Dose 2 and had any follow-up for safety during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	4 6.7%	18 7.5%

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Safety Population who received Dose 2 and had any follow-up for safety during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	2 3.3%	10 4.2%

17. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) Through 28 Days Post Vaccination, 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 birth defect 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 was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days Post Vaccination, 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 was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	0 0%	1 0.4%

19. Secondary Outcome

Title	Number of Participants With SAEs Through 28 Days Post Vaccination, 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 birth defect 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

Participants in the Safety Population for Dose 2 who received Dose 2 and had any follow-up for safety during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	0 0%	0 0%

20. Secondary Outcome

Title	Number of Participants With NOCDs Within 28 Days Post Vaccination, 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

Participants in the Safety Population for Dose 2 who received Dose 2 and had any safety follow-up during the reporting period.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	55	228
Number [Participants]	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With SAEs Through 180 Days Post Final Dose
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 birth defect 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 was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	2 3.3%	3 1.3%

22. Secondary Outcome

Title	Number of Participants With NOCDs Through 180 Days Post Final Dose.
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 was defined as all participants who received at least one dose of investigational product and had any follow-up for safety.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	60	240
Number [Participants]	1 1.7%	1 0.4%

23. Secondary Outcome

Title	Number of Participants Who Achieved a Post Dose 1 (Day 15) HAI Titer ≥ 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 were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	30	120
Number [Participants]	1 1.7%	11 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants 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 CI 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	5.8
	Confidence Interval	(2-Sided) 95%; -7.7 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Number of Participants Who Achieved a Post Dose 1 (Day 29) HAI Titer ≥ 32 Against the H1N1 Strain in All Subjects 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 were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	29	115
Number [Participants]	4 6.7%	9 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants 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 CI 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	-6.0
	Confidence Interval	(2-Sided) 95%; -23.5 to 5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Number of Participants Who Achieved a Post Dose 2 (Day 57) HAI Titer ≥ 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 investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	54	222
Number [Participants]	6 10%	30 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI3414 [Influenza A (H1N1) Vaccine]
	Comments	The number of participants 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 CI 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	2.4
	Confidence Interval	(2-Sided) 95%; -9.3 to 10.8
	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 were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	30	120
Geometric Mean (Full Range) [Titer]	2.64	3.46

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 were randomized at a 1:1 ratio to have their post Dose 1 immunogenicity blood draw on either Day 15 or Day 29. Participants who received Dose 1 of the investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 1 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	29	115
Geometric Mean (Full Range) [Titer]	4.96	3.44

28. Secondary Outcome

Title	Serum HAI GMTs in All Participants Regardless of Baseline Serostatus, Dose 2 (Day 29)
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 investigational product and had valid HAI measurements from blood samples obtained at baseline and post Dose 2 were included in the analysis.

Arm/Group Title	Placebo	MEDI3414 [Influenza A (H1N1) Vaccine]
Arm/Group Description	Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.	MEDI3414 - Monovalent vaccine was supplied in intranasal sprayers containing a total volume of 0.5mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10^7 FFU (fluorescent focus units) of live, attenuated influenza virus reassortant A/California/7/2009 strain that was propagated in chicken eggs. H1N1 monovalent influenza vaccine (MEDI3414) contained no preservatives and no adjuvants.
Measure Participants	54	222
Geometric Mean (Full Range) [Titer]	3.90	4.86

Adverse Events

Time Frame	Safety evaluation consisted of AEs through 7 days and 14 days after each vaccination, SAEs and NOCDs through 28 days after each vaccination, and SAEs and NOCDs through 180 days after the final vaccination.
Adverse Event Reporting Description	Telephone contacts were made by site personnel to the subject at various times during the study to assess safety.
Arm/Group Title	H1N1 Monovalent Vaccine Days 1-15		Placebo Days 1-15		H1N1 Monovalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent Days 58-209		Placebo Days 58-209
Arm/Group Description	A/California/7/2009 strain of the live, attenuated influenza virus reassortant 10^7 FFU that was propagated in chicken eggs. MEDI3414 contained no preservatives and no adjuvants. Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.		Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.		A/California/7/2009 strain of the live, attenuated influenza virus reassortant 10^7 FFU that was propagated in chicken eggs. MEDI3414 contained no preservatives and no adjuvants. Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.		Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.		A/California/7/2009 strain of the live, attenuated influenza virus reassortant 10^7 FFU that was propagated in chicken eggs. MEDI3414 contained no preservatives and no adjuvants. Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.		Placebo (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer). Subjects received two doses by intranasal spray; each dose was administered approximately 28 days apart on Days 1 and 29.
All Cause Mortality
	H1N1 Monovalent Vaccine Days 1-15		Placebo Days 1-15		H1N1 Monovalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent 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 1-15		Placebo Days 1-15		H1N1 Monovalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent 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	0/240 (0%)		0/60 (0%)		0/228 (0%)		0/55 (0%)		3/240 (1.3%)		2/60 (3.3%)
Hepatobiliary disorders
Gallbladder disorder	0/240 (0%)	0	0/60 (0%)	0	0/228 (0%)	0	0/55 (0%)	0	0/240 (0%)	0	1/60 (1.7%)	1
Infections and infestations
Cellulitis	0/240 (0%)	0	0/60 (0%)	0	0/228 (0%)	0	0/55 (0%)	0	1/240 (0.4%)	1	0/60 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	0/240 (0%)	0	0/60 (0%)	0	0/228 (0%)	0	0/55 (0%)	0	0/240 (0%)	0	1/60 (1.7%)	1
Pregnancy, puerperium and perinatal conditions
Premature baby	0/240 (0%)	0	0/60 (0%)	0	0/228 (0%)	0	0/55 (0%)	0	1/240 (0.4%)	1	0/60 (0%)	0
Psychiatric disorders
Depression	0/240 (0%)	0	0/60 (0%)	0	0/228 (0%)	0	0/55 (0%)	0	1/240 (0.4%)	1	0/60 (0%)	0
Other (Not Including Serious) Adverse Events
	H1N1 Monovalent Vaccine Days 1-15		Placebo Days 1-15		H1N1 Monovalent Vaccine Days 29-57		Placebo Days 29-57		H1N1 Monovalent 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	17/240 (7.1%)		9/60 (15%)		13/228 (5.7%)		1/55 (1.8%)		0/240 (0%)		0/60 (0%)
Gastrointestinal disorders
Diarrhoea	4/240 (1.7%)	4	2/60 (3.3%)	2	4/228 (1.8%)	4	0/55 (0%)	0	0/240 (0%)	0	0/60 (0%)	0
Nausea	5/240 (2.1%)	5	2/60 (3.3%)	2	1/228 (0.4%)	1	0/55 (0%)	0	0/240 (0%)	0	0/60 (0%)	0
Infections and infestations
Ear infection	0/240 (0%)	0	2/60 (3.3%)	2	0/228 (0%)	0	0/55 (0%)	0	0/240 (0%)	0	0/60 (0%)	0
Respiratory, thoracic and mediastinal disorders
Sneezing	4/240 (1.7%)	4	2/60 (3.3%)	2	3/228 (1.3%)	3	1/55 (1.8%)	1	0/240 (0%)	0	0/60 (0%)	0
Nasal Congestion	4/240 (1.7%)	4	1/60 (1.7%)	1	5/228 (2.2%)	5	0/55 (0%)	0	0/240 (0%)	0	0/60 (0%)	0

Limitations/Caveats

[Not Specified]

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