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

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 adults.

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 adults.

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

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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 |
| --- | --- |
| Experimental: MEDI3414 [Influenza A (H1N1) vaccine]<br>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]<br>* 0.5 mL; (intranasal sprayer)<br>* Other names: MEDI3414;|
| Placebo Comparator: Placebo<br>Placebo -Placebo was supplied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer. | Other: Placebo<br>* (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 Oral 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 (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% | Days 1-8 | 
| Number of Participants Who Experienced a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | Seroresponse was defined as a ≥ 4-fold rise in hemagglutination inhibition (HAI) titer from baseline. All immunogenicity analyses were based on the immunogenicity population. | Day 1, Day 15 | 
| Number of Participants Who Experienced a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were based on the immunogenicity population. | Day 1, Day 29 | 
| Number of Participants Who Experienced a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All immunogenicity analyses were based on the immunogenicity population. | Day 1, Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 1 | 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. | Days 1-8 | 
| Number of Participants Reporting Adverse Events (AEs) Within 7 Days Post Vaccination, Dose 1 |  | Days 1-8 | 
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days Post Vaccination, Dose 1. |  | Days 1-8 | 
| Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 1 |  | Days 1-15 | 
| Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 1 |  | Days 1-15 | 
| Number of Participant Using Anti-pyretic and Analgesic Agents Within 14 Days Post Vaccination, Dose 1 |  | Days 1-15 | 
| Number of Participants With Any Solicited Symptom Within 7 Days Post Vaccination, Dose 2 |  | Days 29-36 | 
| Number of Participants Reporting AEs Within 7 Days Post Vaccination, Dose 2 |  | Days 29-36 | 
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days Post Vaccination, Dose 2 |  | Days 29-36 | 
| Number of Participants With Any Solicited Symptom Within 14 Days Post Vaccination, Dose 2 |  | Days 29-43 | 
| Number of Participants Reporting AEs Within 14 Days Post Vaccination, Dose 2 |  | Days 29-43 | 
| Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days Post Vaccination, Dose 2 |  | Days 29-43 | 
| Number of Participants With Serious Adverse Events (SAEs) Through 28 Days Post Vaccination, 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 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. | Days 1-29 | 
| Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days Post Vaccination, 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 SAEs Through 28 Days Post Vaccination, 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 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. | Days 29-57 | 
| Number of Participants With NOCDs Within 28 Days Post Vaccination, 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 Through 180 Days Post Final Dose | 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. | Days 1-209 | 
| Number of Participants With NOCDs Through 180 Days Post Final Dose. | 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 Who Achieved a Post Dose 1 (Day 15) HAI Titer ≥ 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 Achieved a Post Dose 1 (Day 29) HAI Titer ≥ 32 Against the H1N1 Strain in All Subjects Regardless of Baseline Serostatus | All immunogenicity analyses are based on the immunogenicity population. | Day 1, Day 29 | 
| 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 | 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 29) | All immunogenicity analyses are based on the immunogenicity population. | Day 1, Day 57 |