Clinical trial NCT00946101: A Study to Evaluate the Safety of HIN1 Monovalent Vaccine (MEDI3414) in Children 2 to 17 Years of Age
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of MEDI3414 in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: randomized, double-blind, placebo-controlled
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2009-07-24
Enrollment: 326
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Fever Post Dose 1 (Days 1-8), Defined as an Axillary Temperature ≥ 101°F (38.3°C).
timeFrame: Days 1- 8
measure: Number of Participants Who Experience a Post Dose 1 (Day 15) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
timeFrame: Day 1, Day 15
measure: Number of Participants Who Experience a Post Dose 1 (Day 29) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
timeFrame: Day 1, Day 29
measure: Number of Participants Who Experience a Post Dose 2 (Day 57) Seroresponse Against the H1N1 Strain in All Participants Regardless of Baseline Serostatus
timeFrame: Day 1, Day 57
Secondary outcomes:
measure: Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-8
measure: Number of Participants Reporting Adverse Events (AEs) Within 7 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-8
measure: Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-8
measure: Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-15
measure: Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-15
measure: Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-15
measure: Number of Participants With Any Solicited Symptoms Within 7 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-36
measure: Number of Participants Reporting AEs Within 7 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-36
measure: Number of Participants Using Anti-pyretic and Analgesic Agents Within 7 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-36
measure: Number of Participants With Any Solicited Symptoms Within 14 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-43
measure: Number of Participants Reporting AEs Within 14 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-43
measure: Number of Participants Using Anti-pyretic and Analgesic Agents Within 14 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-43
measure: Number of Participants With New Onset Chronic Diseases (NOCDs) Within 28 Days After Vaccination With Investigational Product, Dose 1.
timeFrame: Days 1-29
measure: Number of Participants With Serious Adverse Events (SAEs) Within 28 Days After Vaccination With Investigational Product, Dose 1
timeFrame: Days 1-29
measure: Number of Participants With NOCDs Within 28 Days After Vaccination With Investigational Product, Dose 2.
timeFrame: Days 29-57
measure: Number of Participants With SAEs Within 28 Days After Vaccination With Investigational Product, Dose 2
timeFrame: Days 29-57
measure: Number of Participants With NOCDs Within 180 Days Post Final Dose of Investigational Product.
timeFrame: Days 1-209
measure: Number of Participants With SAEs Within 180 Days Post Final Dose of Investigational Product.
timeFrame: Days 1-209
measure: 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.
timeFrame: Day 1, Day 15
measure: 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.
timeFrame: Day 1, Day 29
measure: 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.
timeFrame: Day 1, Day 57
measure: Serum HAI Geometric Mean Titers (GMTs) in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 15)
timeFrame: Day 1, Day 15
measure: Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 1 (Day 29)
timeFrame: Day 1, Day 29
measure: Serum HAI GMTs in All Participants, Regardless of Baseline Serostatus, Dose 2 (Day 57)
timeFrame: Day 1, Day 57
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinic Research, Inc.
state: Alabama
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: San Francisco
country: United States
facility: Benchmark Research
state: California
city: Bardstown
country: United States
facility: Kentucky Pediatric Research Center
state: Kentucky
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: St. Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Henderson
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research Inc.
state: New York
city: Pittsburgh
country: United States
facility: Primary Physicians Research, Inc.
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Ft. Worth
country: United States
facility: Benchmark Research Ft. Worth
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research San Angelo
state: Texas
Study officials:
affiliation: MedImmune LLC
name: Elissa Malkin, D.O.
role: STUDY_DIRECTOR
References:
citation: 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.