Safety and Tolerability Study of GlaxoSmithKline (GSK)1557484A Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure

GlaxoSmithKline50 enrolled

Overview

The purpose of this study is to evaluate the safety and tolerability of GSK Biologicals' vaccine GSK1557484A against pandemic avian (H5N1) influenza in adults at occupational risk of exposure to the virus.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Influenza Influenza Vaccines

Interventions

Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia)BIOLOGICAL

2 doses administered intramuscularly (IM) in deltoid region of arm at the Day 0 and Day 21 visits.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects who, in the opinion of the investigator can and will comply with the requirements of the protocol. * Male or female adults ≥18 years of age at time of first study vaccination. * Written informed consent obtained from the subject. * Subjects who are at risk of occupational exposure to H5N1 influenza viruses based on exposure, or potential exposure during either (a) laboratory operations with live H5N1 virus, (b) production of H5N1 vaccines, or (c) conduct of epidemiological investigations of H5N1 cases. * Stable health status as defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 30 days prior to enrollment. * Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause. * Female subjects of childbearing potential may be enrolled in the study, if they have practiced adequate contraception for 30 days prior to vaccination, and have a negative pregnancy test on the day of vaccination, and agree to practice adequate contraception for two months following the last dose of vaccine. Exclusion Criteria: * Presence or evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. * Presence of a temperature ≥ 38.0ºC (≥100.4ºF) or acute symptoms greater than "mild" severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied. * Significant risk of complications from intramuscular injections due to disorder of coagulation. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. Assessment of risk of injection complications should be made in the context of individual subject risk of H5N1 virus infection. * An acute evolving neurological disorder or Guillain Barré Syndrome within 42 days of receipt of prior seasonal or pandemic influenza vaccine. * Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first dose of study vaccine. * Planned administration of any vaccine other than the study vaccine before Day 42. * Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine including a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. * Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result before the first vaccination. * Lactating or nursing women. * Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Locations (3)

GSK Investigational Site

Stockbridge, Georgia, United States

GSK Investigational Site

Rockville, Maryland, United States

GSK Investigational Site

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Overall and by Age Category (18-64 and >64 Years of Age).

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. \>100mm.

Time frame: During a 7-day follow-up period (Days 0-6) after each vaccination

Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Overall and by Age Category (18-64 and >64 Years of Age).

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain, muscle ache, shivering, sweating and fever \[oral temperature above 38.0 degrees Celsius (°C)\]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature ≥ 39.0°C and ≤40°C.

Time frame: During a 7-day follow-up period (Days 0-6) after each vaccination

Number of Subjects Reporting Any Unsolicited AEs, Overall and by Age Category (18-64 and >64 Years of Age)

Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Related was defined as an unsolicited symptom assessed as causally related to the study vaccination.

Time frame: During the 21-day (Days 0-20 post dose 1 and Days 21-41 post dose 2) post-vaccination period

Secondary Outcomes

Number of Subjects Reporting Any or Related Medically Attended Adverse Events (MAEs)

Data from ClinicalTrials.gov

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MAEs refer to events that required medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Related = symptom assessed by the investigator as causally related to the study vaccination.

Time frame: During the entire study period (Day 0 to Day 385)

Number of Subjects Reporting Any and Related Potential Immune-Mediated Diseases (pIMDs)

Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events (AEs) that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any was defined as occurrence of any pIMD regardless of intensity grade or relation to vaccination. Related was defined as pIMD(s) considered by the investigator to have a causal relationship to vaccination.

Time frame: During the entire study period (Day 0 to Day 385)

Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)

A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Time frame: During the entire study period (Day 0 to Day 385)

Number of Subjects With Reported Adverse Pregnancy Outcomes

Any = Occurrence of any adverse pregnancy outcomes regardless of intensity grade or relation to study vaccination. Related = Adverse pregnancy outcomes assessed by the investigator as causally related to the study vaccination

Time frame: During the entire study period (Day 0 to Day 385)

Assessment of Changes From Baseline (Day 0) in the SF-36v2 Daily Questionnaire Subscale Component, Summary Component and QALY Scores

The assessed parameters for change from baseline were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) defined as subscale component, and physical (PCS) and mental (MCS) component defined as summary components, and Quality Adjusted Life Years (QALY). See methodology details in outcome 11 description. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Subscale component scores are averaged to compute the summary component score and QALY score. Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. Analyses by age category were not performed for the daily SF-36v2 questionnaire results.

Time frame: Day 0 (baseline) and at each day from Day 1 to Day 7 post first vaccine dose

Assessment of Changes From Baseline (Day 0) in the SF-36v2 Weekly Health 8-score