Influenza
Conditions
Keywords
randomized, double-blind, placebo-controlled
Brief summary
The purpose of this study was to determine the safety and descriptive immunogenicity of the H1N1 influenza vaccine in healthy children.
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.
Interventions
BIOLOGICALMEDI3414 [Influenza A(H1N1) live attenuated, intranasal]
0.5 mL: (intranasal sprayer)
BIOLOGICALPlacebo
Placebo was supplied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer
Sponsors
Department of Health and Human Services
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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%. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1 | Days 1-15 | — |
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1 | Days 1-15 | — |
| Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2 | Days 29-36 | — |
| Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2 | Days 29-36 | — |
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2 | Days 29-36 | — |
| Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2 | Days 29-43 | — |
| Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2 | Days 29-43 | — |
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2 | Days 29-43 | — |
| 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). |
| 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. |
| 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. |
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1 | Days 1-8 | — |
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1 | Days 1-8 | — |
| Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1 | Days 1-15 | — |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| H1N1 Monovalent Influenza Vaccine 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. | 261 |
| Placebo 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. | 65 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal of consent | 2 | 0 |
Baseline characteristics
| Characteristic | H1N1 Monovalent Influenza Vaccine | Total | Placebo |
|---|---|---|---|
| Age Continuous | 8.9 years STANDARD_DEVIATION 4.3 | 9.0 years STANDARD_DEVIATION 4.3 | 9.2 years STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 67 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 211 Participants | 259 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 participants | 4 participants | 0 participants |
| Race (NIH/OMB) Asian | 2 participants | 6 participants | 4 participants |
| Race (NIH/OMB) Black or African American | 43 participants | 55 participants | 12 participants |
| Race (NIH/OMB) More than one race | 8 participants | 9 participants | 1 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 participants | 2 participants | 0 participants |
| Race (NIH/OMB) Other | 4 participants | 9 participants | 5 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) White | 198 participants | 241 participants | 43 participants |
| Sex: Female, Male Female | 130 Participants | 166 Participants | 36 Participants |
| Sex: Female, Male Male | 131 Participants | 160 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 259 | 2 / 65 | 11 / 255 | 3 / 63 | 0 / 255 | 0 / 63 |
| serious Total, serious adverse events | 1 / 259 | 0 / 65 | 0 / 255 | 0 / 63 | 1 / 259 | 1 / 65 |
Outcome results
Primary
Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 10 participants |
| Placebo | Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 2 participants |
Comparison: 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).95% CI: [-12.8, 9.8]score
Primary
Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 14 participants |
| Placebo | Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 2 participants |
Comparison: 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).95% CI: [-9.6, 13.8]score
Primary
Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 80 participants |
| Placebo | Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | 9 participants |
Comparison: 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).95% CI: [5.5, 27.1]score
Primary
Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C).
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C). | 4 participants |
| Placebo | Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C). | 1 participants |
Comparison: 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%95% CI: [-6.4, 3.1]score
Secondary
Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1
Time frame: Days 1-8
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1 | 28 participants |
| Placebo | Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1 | 7 participants |
Secondary
Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1
Time frame: Days 1-15
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1 | 47 participants |
| Placebo | Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1 | 11 participants |
Secondary
Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-43
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2 | 35 participants |
| Placebo | Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2 | 9 participants |
Secondary
Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-36
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2 | 20 participants |
| Placebo | Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2 | 2 participants |
Secondary
Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1
Time frame: Days 1-15
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1 | 27 participants |
| Placebo | Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1 | 2 participants |
Secondary
Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-43
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2 | 22 participants |
| Placebo | Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2 | 11 participants |
Secondary
Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1
Time frame: Days 1-8
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1 | 18 participants |
| Placebo | Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1 | 1 participants |
Secondary
Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-36
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2 | 10 participants |
| Placebo | Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2 | 5 participants |
Secondary
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.
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 15
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | 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. | 13 participants |
| Placebo | 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. | 1 participants |
Comparison: 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).95% CI: [-6.1, 14.7]score
Secondary
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.
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 29
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | 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. | 13 participants |
| Placebo | 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. | 1 participants |
Comparison: 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).95% CI: [-5.8, 15.1]score
Secondary
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.
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 57
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | 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. | 66 participants |
| Placebo | 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. | 6 participants |
Comparison: 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).95% CI: [5.9, 25.2]score
Secondary
Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1
Time frame: Days 1-15
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1 | 122 participants |
| Placebo | Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1 | 22 participants |
Comparison: 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.95% CI: [-0.4, 25.7]score
Secondary
Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-43
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2 | 93 participants |
| Placebo | Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2 | 27 participants |
Comparison: 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.95% CI: [-20.3, 7.1]score
Secondary
Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1 | 97 participants |
| Placebo | Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1 | 21 participants |
Comparison: 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.95% CI: [-8.4, 17.6]score
Secondary
Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2
Time frame: Days 29-36
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2 | 65 participants |
| Placebo | Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2 | 20 participants |
Comparison: 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.95% CI: [-19.7, 6.1]score
Secondary
Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1. | 0 participants |
| Placebo | Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1. | 0 participants |
Secondary
Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product. | 0 Participants |
| Placebo | Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product. | 1 Participants |
Secondary
Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2. | 0 participants |
| Placebo | Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2. | 1 participants |
Secondary
Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product. | 2 participants |
| Placebo | Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product. | 1 participants |
Secondary
Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2 | 0 participants |
| Placebo | Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2 | 0 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1 | 1 participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1 | 0 participants |
Secondary
Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15)
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 15
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15) | 3.55 titer |
| Placebo | Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15) | 2.89 titer |
Secondary
Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29)
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 29
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29) | 3.53 titer |
| Placebo | Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29) | 2.71 titer |
Secondary
Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57)
All immunogenicity analyses are based on the immunogenicity population.
Time frame: Day 1, Day 57
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| H1N1 Monovalent Influenza Vaccine | Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57) | 7.61 titer |
| Placebo | Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57) | 3.70 titer |