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

• ClinicalTrials.gov Identifier: NCT00945893
• Recruitment Status: Completed
• First Posted: July 24, 2009
• Results First Posted: September 5, 2011
• Last Update Posted: September 12, 2011
• Sponsor: MedImmune LLC
• Collaborator: Department of Health and Human Services
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: July 23, 2009
• First Posted Date: July 24, 2009
• Results First Submitted Date: June 17, 2011
• Results First Posted Date: September 5, 2011
• Last Update Posted Date: September 12, 2011
• Study Start Date: August 2009
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2011)

• Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Oral Temperature ≥ 101°F (38.3°C). [ Time Frame: 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%
• Number of Participants Who Experienced a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [ Time Frame: 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.
• Number of Participants Who Experienced a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [ Time Frame: 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.
• Number of Participants Who Experienced a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: July 23, 2009): The primary safety endpoint of this study is fever post Dose 1; the primary immunogenicity endpoint is the proportion of subjects who experience a post-dose seroresponse against the H1N1 Strain. [ Time Frame: (Safety) Days 1-14 ]

Current Secondary Outcome Measures (submitted: September 6, 2011)

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

• Original Secondary Outcome Measures (submitted: July 23, 2009): To assess other solicited symptoms, antipyretic and analgesic use, and AEs that occur within 7 days post-dose with investigational product; secondary immunogenicity endpoints: include the post dose strain-specific serum HAI antibody geometric mean titers [ Time Frame: Day 1 and Day 29 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety of H1N1 Monovalent Vaccine (MEDI3414) in Healthy Adults
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of MEDI3414 in Adults
• Brief Summary: The purpose of this study was to determine the safety and descriptive immunogenicity of the H1N1 influenza vaccine in healthy adults.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Healthy

Intervention

• Biological: MEDI3414 [Influenza A/H1N1 live attenuated, intranasal]
  0.5 mL; (intranasal sprayer)
  Other Name: MEDI3414
• Other: Placebo
  (intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer)

Study Arms

• 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.
  Intervention: Biological: MEDI3414 [Influenza A/H1N1 live attenuated, intranasal]
• Placebo Comparator: Placebo
  Placebo -Placebo was supplied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer.
  Intervention: Other: Placebo

• Publications *: Mallory RM, Malkin E, Ambrose CS, Bellamy T, Shi L, Yi T, Jones T, Kemble G, Dubovsky F. Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials. PLoS One. 2010 Oct 29;5(10):e13755. doi: 10.1371/journal.pone.0013755.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 23, 2009): 300
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 49 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00945893
• Other Study ID Numbers: MI-CP215; HHS/ASPR ( Other Grant/Funding Number: HHSO100200900002I )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: MedImmune LLC
• Study Sponsor: MedImmune LLC
• Collaborators: Department of Health and Human Services

Investigators

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

• PRS Account: MedImmune LLC
• Verification Date: September 2011