Healthy or Stable Chronic Illness Clinical Trial
— LAIVOfficial title:
A Randomized, Double-Blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children
| Verified date | September 2011 |
| Source | MedImmune LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
The primary objective of this study is to demonstrate the immunologic noninferiority of Q/LAIV to FluMist in children 2 to 17 years of age.
| Status | Completed |
| Enrollment | 2312 |
| Est. completion date | December 2010 |
| Est. primary completion date | July 2010 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 2 Years to 17 Years |
| Eligibility |
Inclusion Criteria: - Male or female - Age 2 through 17 years at the time of randomization - Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU, and written informed assent if applicable) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations - Females of childbearing potential, unless surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), has sterile male partner, is premenarchal, or practices abstinence, must have used an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap with spermicide, 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 final dose of investigational product - A subject who is considered by the investigator to be at risk of pregnancy must also have a negative urine pregnancy test at screening and, if screening and Day 0 do not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment is required to assess each subject's need for pregnancy testing - Healthy by medical history and physical examination OR presence of stable underlying chronic medical condition for which hospitalization has not been required in the previous year - Able to complete follow-up period of 180 days post last dose of vaccine as required by the protocol - Subject/legal representative is available by telephone - Child's legal representative is able to understand and comply with the requirements of the protocol, as judged by the investigator Exclusion Criteria: - Acute illness or evidence of significant active infection at randomization; - Fever = 100.4°F (38.0°C) at randomization - History of asthma, or in children < 5 years of age, history of recurrent wheezing - Any drug therapy from 15 days prior to randomization or expected drug therapy through 28 days post last dose with the exception of the following classes/types of medications, which are allowed: - Contraceptives (change in contraceptive type or method is acceptable as long as guidelines are followed for prevention of pregnancy during change); - Topical corticosteroids, calcineurin inhibitors, or antifungals for uncomplicated dermatitis; - Chronic medications (including those taken on an as-needed basis) that have been well tolerated and were not initiated and/or did not have a dosage change within 90 days prior to randomization. - Current or expected receipt of immunosuppressive medications within a 28 day window around any dose, including an immunosuppressive dose of corticosteroids, which is defined as = 20 mg/day of prednisone or its equivalent, given daily or on alternate days for = 15 days) (intranasal, intra-articular, and topical corticosteroids are permitted); Note: topical corticosteroids for uncomplicated dermatitis may be used throughout the study according to the judgment of the investigator; topical calcineurin inhibitors may be used in accordance with their package insert at entry and during study participation - Receipt of immunoglobulin or blood products within 90 days before randomization into the study or expected receipt during study participation - Receipt of any investigational drug therapy within 28 days prior to Dose 1 or planned receipt of any investigational drug therapy through 90 days after final dosing of investigational product (use of licensed agents for indications not listed in the package insert is permitted) - Receipt of any nonstudy vaccine within 28 days prior to randomization or planned receipt of nonstudy vaccine through 28 days after final dosing - Receipt of any nonstudy seasonal influenza vaccine within 90 days of Dose 1 or planned receipt of nonstudy seasonal influenza vaccine prior to 35 days post last dose of investigational product - Any known immunosuppressive condition or immune deficiency disease including known or suspected infection with human immunodeficiency virus (HIV) - History of allergic disease or reactions likely to be exacerbated by any component of the investigational product including allergy to eggs, egg proteins, gentamicin, or gelatin or serious, life threatening, or severe reactions to previous influenza vaccinations - Use of aspirin or salicylate-containing products within 28 days prior to randomization or expected receipt through 28 days after final vaccination; - History of Guillain-Barré syndrome - Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir, and zanamivir) within 28 days prior to first dose of investigational product or anticipated use of such agents within 28 days after last scheduled vaccination - Known or suspected mitochondrial encephalomyopathy - Pregnant or lactating female - History of alcohol or drug abuse that, in the opinion of the investigator, would affect the subject's safety or compliance with study - Any condition that, in the opinion of the investigator, might compromise the safety of the subject in the study or would interfere with evaluation of the safety or immunogenicity of the investigational products - Subject, legal representative, or immediate family member of subject who is an employee of the clinical study site or who is otherwise involved with the conduct of the study - A history of epilepsy, seizure, or an evolving neurological condition except that of a single febrile seizure that occurred 3 or more years prior to enrollment would not disqualify a subject Note: an individual who initially is excluded from study participation based on one or more of the above time-limited criteria may be reconsidered for enrollment once the condition has resolved as long as the subject continues to meet all other entry criteria and the same SID number is used |
Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| United States | Research Site | Akron | Ohio |
| United States | Research Site | Albuquerque | New Mexico |
| United States | Research Site | Altoona | Pennsylvania |
| United States | Research Site | Anaheim | California |
| United States | Research Site | Arlington | Texas |
| United States | Research Site | Asheboro | North Carolina |
| United States | Research Site | Bardstown | Kentucky |
| United States | Research Site | Benton | Arkansas |
| United States | Research Site | Bentonville | Arkansas |
| United States | Research Site | Binghamton | New York |
| United States | Research Site | Birmingham | Alabama |
| United States | Research Site | Bismark | North Dakota |
| United States | Research Site | Boca Raton | Florida |
| United States | Research Site | Boone | North Carolina |
| United States | Research Site | Bristol | Tennessee |
| United States | Research Site | Brooklyn | New York |
| United States | Research Site | Burke | Virginia |
| United States | Research Site | Charleston | South Carolina |
| United States | Research Site | Charleston | South Carolina |
| United States | Research Site | Charlottesville | Virginia |
| United States | Research Site | Chicago | Illinois |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Clarksville | Tennessee |
| United States | Research Site | Clyde | North Carolina |
| United States | Research Site | Dalton | Georgia |
| United States | Research Site | Dayton | Ohio |
| United States | Research Site | Dekalb | Illinois |
| United States | Research Site | Draper | Utah |
| United States | Research Site | Erie | Pennsylvania |
| United States | Research Site | Fargo | North Dakota |
| United States | Research Site | Fayetteville | Arkansas |
| United States | Research Site | Fountain Valley | California |
| United States | Research Site | Franklin | Wisconsin |
| United States | Research Site | Fresno | California |
| United States | Research Site | Ft. Worth | Texas |
| United States | Research Site | Ft. Worth | Texas |
| United States | Research Site | Greenville | Pennsylvania |
| United States | Research Site | Harleysville | Pennsylvania |
| United States | Research Site | Hermitage | Pennsylvania |
| United States | Research Site | Huber Heights | Ohio |
| United States | Research Site | Huntington | West Virginia |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Jonesboro | Arkansas |
| United States | Research Site | Kalamazoo | Michigan |
| United States | Research Site | Kansas City | Missouri |
| United States | Research Site | Kingsport | Tennessee |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Latrobe | Pennsylvania |
| United States | Research Site | Layton | Utah |
| United States | Research Site | Lebanon | New Hampshire |
| United States | Research Site | Lexington | Kentucky |
| United States | Research Site | Little Rock | Arkansas |
| United States | Research Site | Long Beach | California |
| United States | Research Site | Longview | Texas |
| United States | Research Site | Marietta | Georgia |
| United States | Research Site | Metairie | Louisiana |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Mineola | New York |
| United States | Research Site | Mobile | Alabama |
| United States | Research Site | Mount Pleasant | North Carolina |
| United States | Research Site | Mt. Pleasant | South Carolina |
| United States | Research Site | Nashville | Tennessee |
| United States | Research Site | New Branfels | Texas |
| United States | Research Site | Newton | Kansas |
| United States | Research Site | Niles | Michigan |
| United States | Research Site | Norman | Oklahoma |
| United States | Research Site | Omaha | Nebraska |
| United States | Research Site | Omaha | Nebraska |
| United States | Research Site | Orem | Utah |
| United States | Research Site | Overland Park | Kansas |
| United States | Research Site | Papillion | Nebraska |
| United States | Research Site | Paramount | California |
| United States | Research Site | Pittsburgh | Pennsylvania |
| United States | Research Site | Pittsburgh | Pennsylvania |
| United States | Research Site | Pittsburgh | Pennsylvania |
| United States | Research Site | Pittsburgh | Pennsylvania |
| United States | Research Site | Plymouth | Minnesota |
| United States | Research Site | Ponte Vedra | Florida |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Rochester | New York |
| United States | Research Site | Rochester | New York |
| United States | Research Site | Roy | Utah |
| United States | Research Site | Sacramento | California |
| United States | Research Site | Salt Lake City | Utah |
| United States | Research Site | San Francisco | California |
| United States | Research Site | Scotland | Pennsylvania |
| United States | Research Site | Sellersville | Pennsylvania |
| United States | Research Site | South Jordan | Utah |
| United States | Research Site | South Miami | Florida |
| United States | Research Site | St. Louis | Missouri |
| United States | Research Site | St. Louis | Missouri |
| United States | Research Site | St. Paul | Minnesota |
| United States | Research Site | St. Petersburg | Florida |
| United States | Research Site | Stevensville | Michigan |
| United States | Research Site | Sugarland | Texas |
| United States | Research Site | Syracuse | Utah |
| United States | Research Site | Tucson | Arizona |
| United States | Research Site | Vienna | Virginia |
| United States | Research Site | Virginia Beach | Virginia |
| United States | Research Site | West Covina | California |
| United States | Research Site | West Palm Beach | Florida |
| United States | Research Site | Wichita | Kansas |
| United States | Research Site | Wilmington | Delaware |
| United States | Research Site | Winston-Salem | North Carolina |
| United States | Research Site | Woodstock | Georgia |
| United States | Research Site | Yukon | Oklahoma |
| Lead Sponsor | Collaborator |
|---|---|
| MedImmune LLC |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The 4 Post-dose Strain-specific Serum Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) in the Q/LAIV (MEDI3250) Arm Are Noninferior to Those in the Comparator FluMist Group. | Noninferior immune response was defined as having the upper bound of the 2-sided 95% confidence intervals (CIs) for the HAI antibody GMT ratio (FluMist comparator divided by Q/LAIV) = 1.5 for each of the 4 strains. . | Day 28 post immunogenicity dose | No |
| Secondary | The Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose | Seroresponse was defined as a = 4-fold rise in HAI antibody titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose | Seroresponse was defined as a = 4-fold rise in HAI antibody titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose | Seroresponse was defined as a = 4-fold rise in HAI antibody titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose | Seroresponse was defined as a = 4-fold rise from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Victoria Strain Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. Seroresponse was defined as a = 4-fold rise in HAI titer from baseline. | Day 0 and Day 28 post immunogenicity dose | No |
| Secondary | Percent of Participants (Regardless of Serostatus) Who Achieved an A/H1N1 or A/H3N2 Strain-specific HAI Antibody Titer = 32 Post Immunogenicity Dose | Day 28 post immunogenicity dose | No | |
| Secondary | Percent of Participants (Regardless of Serostatus) Who Achieved a B/Yamagata HAI Antibody Titer = 32 Post Immunogenicity Dose | Day 28 post immunogenicity dose | No | |
| Secondary | Percent of Participants (Regardless of Serostatus) Who Achieved a B/Victoria HAI Antibody Titer = 32 Post Immunogenicity Dose | Day 28 post immunogenicity dose | No | |
| Secondary | Percent of Serosusceptible Participants Who Achieved an A/H1N1 HAI Antibody Titer = 32 Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Who Achieved an A/H3N2 HAI Antibody Titer = 32 Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Who Achieved a B/Yamagata HAI Antibody Titer = 32 Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Serosusceptible Participants Who Achieved a B/Victoria HAI Antibody Titer = 32 Post Immunogenicity Dose | Serosusceptible was defined as a baseline HAI titer = 8. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Who Achieved an A/H1N1 HAI Antibody Titer = 32 Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Who Achieved an A/H3N2 HAI Antibody Titer = 32 Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Who Achieved a B/Yamagata HAI Antibody Titer = 32 Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of Seronegative Participants Who Achieved a B/Victoria HAI Antibody Titer = 32 Post Immunogenicity Dose | Seronegative was defined as a baseline HAI titer = 4. | Day 28 post immunogenicity dose | No |
| Secondary | Percent of All Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 | Solicited symptoms were fever = 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. | Days 0-14 Post Dose 1 | Yes |
| Secondary | Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 | Solicited symptoms were fever = 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. | Days 0-14 Post Dose 1 | Yes |
| Secondary | Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Dose 2 During Days 0-14 Post Dose 2 | Solicited symptoms were fever = 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. | Days 0-14 Post Dose 2 | Yes |
| Secondary | Percent of All Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 | Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Days 0-28 Post Dose 1 | Yes |
| Secondary | Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 | Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Days 0-28 Post Dose 1 | Yes |
| Secondary | Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Dose 2 Through 28 Days Post Dose 2 | Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Days 0-28 Post Dose 2 | Yes |
| Secondary | Percent of All Participants Reporting Any Serious Adverse Event (SAE) From Administration of Investigational Product Through Day 28 Post 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 judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. | Days 0-28 Post Dose 1 | Yes |
| Secondary | Percent of Two-dose Participants Reporting Any SAE From Administration of Dose 2 During Days 0-28 Post 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 judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. | Days 0-28 Post Dose 2 | Yes |
| Secondary | Percent of All Participants Reporting Any SAE From Administration of Investigational Product Through 180 Days Post Last 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 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 judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. | Days 0-180 Post Last Dose | Yes |
| Secondary | Percent of All Participants Reporting Any New Onset Chronic Disease (NOCD) From Administration of Investigational Product Through 180 Days Post Last 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. | Days 0-180 Post Last Dose | Yes |