A Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Adults 18 to 49 Years of Age

MedImmune LLC1,800 enrolled

Overview

The objective of this study was to show that quadrivalent live attenuated influenza vaccine (Q/LAIV; MEDI3250) produced antibody levels similar to those produced by the commercial vaccine, FluMist.

This randomized, double-blind, active controlled, multicenter study enrolled 1,800 subjects who were 18 to 49 years of age. Subjects were randomized by site in a 4:1:1 fashion to receive a single dose of Q/LAIV, trivalent FluMist containing an influenza B strain from the Yamagata lineage (FluMist/B/Yamagata), or trivalent FluMist containing an influenza B strain from the Victoria lineage (FluMist/B/Victoria). The study was conducted at multiple sites in the USA in the influenza off-season.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,800

Conditions

Healthy or Stable Underlying Chronic Medical Condition

Interventions

Q/LAIV (MEDI3250)BIOLOGICAL

0.2 mL dose at Day 0

FluMist/B/YamagataBIOLOGICAL

0.2 mL dose at Day 0

FluMist/B/VictoriaBIOLOGICAL

0.2 mL dose at Day 0

Eligibility

Sex: ALLMin age: 18 YearsMax age: 49 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female age 18 to 49 years, inclusive, on the day of randomization (reached his or her eighteenth year birthday but not yet reached his or her 50th year birthday) at the time of the dose of blinded investigational product * Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations * Females of child-bearing potential, (ie, unless surgically sterile \[eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\], had a sterile male partner, was at least 1 year post-menopausal, or practiced 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, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of investigational product, and must have agreed to continue using such precautions for 60 days after the dose of investigational product. In addition, the subject must also have had a negative urine or blood pregnancy test at screening and, if screening and Day 0 did not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment was required to assess a female subject's capability of pregnancy. * Healthy by medical history and physical examination OR presence of stable underlying chronic medical condition for which hospitalization was not required in the previous year * Able to complete follow-up period of 180 days post dose of vaccine as required by the protocol * Subject available by telephone * 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°C) at randomization * History of asthma * Any drug therapy from 15 days prior to randomization or expected drug therapy through 30 days post dose with the exception of contraceptives or chronic medications that were well tolerated and were not initiated and/or did not have a dosage change within 90 days of randomization. * Previous medical history or evidence of an intercurrent illness that might have compromised the safety of the subject in the study * Current or expected receipt of immunosuppressive medications (inhaled and topical corticosteroids were permitted) including corticosteroids (≥ 20 mg/day of prednisone equivalent given daily or on alternate days for ≥ 14 days) within a 30-day window around dose of investigational product Note: topical corticosteroids for uncomplicated dermatitis were permitted according to the judgment of the investigator; topical calcineurin inhibitors were permitted 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 or standard vaccine within 30 days before the dose of investigational product in this study through 30 days after the dose of investigational product (use of licensed agents for indications not listed in the package insert was permitted) * 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 * History of Guillain-Barré syndrome * Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir and zanamivir) within 30 days prior to dose of investigational product or anticipated use within 30 days after vaccination * Known or suspected mitochondrial encephalomyopathy * Lactating woman * History of alcohol or drug abuse that, in the opinion of the investigator, would have affected the subject's safety or compliance with study * Any condition that, in the opinion of the investigator, would have interfered with evaluation of the investigational product or interpretation of subject safety or study results * Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals

Locations (18)

Benchmark Research

Sacramento, California, United States

California Research Foundation

San Diego, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Day 28-35

Secondary Outcomes

The Number of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experience Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.

Time frame: Day 0 and Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience A/H1N1 Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \<= 8 were considered to be serosusceptible for that strain.

Time frame: Day 0 and Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience A/H3N2 Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \<= 8 were considered to be serosusceptible for that strain.

Time frame: Day 0 and Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience B/Yamagata Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \<= 8 were considered to be serosusceptible for that strain.

Time frame: Day 0 and Day 28-35

Data from ClinicalTrials.gov

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Benchmark Research

San Francisco, California, United States

University Clinical Research-Deland, LLC

DeLand, Florida, United States

Pharmax Research Clinic, Inc

Miami, Florida, United States

University Clinical Research, Inc

Pembroke Pines, Florida, United States

Miami Research Associates

South Miami, Florida, United States

Clinical Research Atlanta

Stockbridge, Georgia, United States

Vince and Associates Clinical Research

Overland Park, Kansas, United States

Kentucky Pediatric / Adult Research

Bardstown, Kentucky, United States

...and 8 more locations

The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience B/Victoria Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \<= 8 were considered to be serosusceptible for that strain.

Time frame: Day 0 and Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Experience A/H1N1 Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 0 and Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Experience A/H3N2 Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 0 and Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Experience B/Yamagata Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 0 and Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Experience B/Victoria Strain-specific Seroresponse Post Dose.

Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 0 and Day 28-35

The Number of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Achieved a Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Time frame: Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a A/H1N1 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a strain-specific baseline HAI titer ≤ 8 were considered to be serosusceptible to that strain.

Time frame: Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a strain-specific baseline HAI titer ≤ 8 were considered to be serosusceptible to that strain.

Time frame: Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a B/Yamagata Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a strain-specific baseline HAI titer ≤ 8 were considered to be serosusceptible to that strain.

Time frame: Day 28-35

The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a B/Victoria Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a strain-specific baseline HAI titer ≤ 8 were considered to be serosusceptible to that strain.

Time frame: Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a A/H1N1 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a B/Yamagata Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 28-35

The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a B/Victoria Strain-specific HAI Antibody Titer ≥ 32 Post Dose.

Participants with a baseline HAI titer \> 8 were considered to be seropositive for that strain.

Time frame: Day 28-35

The Number of Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Vaccination

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.

Time frame: Days 0-14

The Number of Participants Reporting Any Adverse Event From Administration of Investigational Product Through 28 Days Post Vaccination

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

Time frame: Days 0-28 post vaccination

Number of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 28 Days Post Vaccination

Serious adverse events were those that resulted in death; were 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 study participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization but that, based on appropriate medical judgment, may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above.

Time frame: Days 0-28 post vaccination

Number of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 180 Days Post Vaccination

Time frame: Days 0-180 post vaccination

Number of Participants Reporting New Onset Chronic Diseases From Administration of Investigational Product Through 180 Days Post Vaccination

An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant.

Time frame: Days 0-180 post vaccination