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

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

Detailed Description
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of MEDI3414 in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: MEDI3414 [Influenza A(H1N1) live attenuated, intranasal]
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | Days 1- 8 | 
| 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. | Day 1, Day 15 | 
| 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. | Day 1, Day 29 | 
| 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. | Day 1, Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 1-8 | 
| 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 | 
| 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. | 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). | Days 1-29 | 
| 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. | Days 1-29 | 
| 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). | Days 29-57 | 
| 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. | Days 29-57 | 
| 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). | Days 1-209 | 
| 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. | Days 1-209 | 
| 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. | Day 1, Day 15 | 
| 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. | Day 1, Day 29 | 
| 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. | Day 1, Day 57 | 
| 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. | Day 1, Day 15 | 
| Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29) | All immunogenicity analyses are based on the immunogenicity population. | Day 1, Day 29 | 
| Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57) | All immunogenicity analyses are based on the immunogenicity population. | Day 1, Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized, double-blind, placebo-controlled