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InfluenzaPhase 3NCT01788228

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

A Phase 3 study testing Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) in people with Influenza and Influenza Vaccines, run by GlaxoSmithKline at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Influenza, Influenza Vaccines
What is being tested?
Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesUnited States
Study dates
22 Mar 2013to 25 Feb 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • GSK Investigational Site

    Madison, Wisconsin, 53715

  • GSK Investigational Site

    Rockville, Maryland, 20850

  • GSK Investigational Site

    Stockbridge, Georgia, 30281

Other trials in United States

About this study

Official title: Safety and Tolerability of GSK 1557484A Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure

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.

Being tested
Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia)
Keywords
Vaccine, Occupational exposure, Influenza, H5N1
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called GSK1557484A vaccine

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

Study groups in NCT01788228
Study groupRoleWhat they receive
Influenza A (H5N1) Virus monovalent vaccine 18-64 Years GroupExperimentalSubjects 18-64 years of age received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) at Days 0 and 21. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm at Day 0 and dominant arm at Day 21.
Receives: Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia)
Influenza A (H5N1) Virus monovalent vaccine > 64 Years GroupExperimentalSubjects >64 years of age received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) at Days 0 and 21. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm at Day 0 and dominant arm at Day 21.
Receives: Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

Secondary outcomes (14)
  1. Number of Subjects Reporting Any or Related Medically Attended Adverse Events (MAEs)

    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.

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

  2. 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.

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

  3. 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.

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

  4. 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

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

  5. 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.

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

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

    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. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Median and range of the change from baseline of the SF-36 score are presented for each component and time point. Analysis was carried out for all subjects regardless of age stratum.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  7. Assessment of Changes From Baseline (Day 0) in the SF-36v2 Weekly Questionnaire General Health Scores (Physical and Mental)

    The assessed parameters for change from baseline were physical and mental component defined as summary components (PCS and MCS) or general health scores (GHS). For all subscale component, 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. Median and range of the change from baseline of the SF-36v2 score are presented for each summary component and time point. Analysis was carried out for all subjects regardless of age stratum.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  8. Assessment of Changes From Baseline (Day 0) for Quality Adjusted Life Years (QALY) Weekly Scores

    The assessed parameters for change from baseline were QALY scores. The methodology used for the analysis of the SF-36v2 questionnaire was detailed in Ware et al [Ware 2008]. The QualityMetric Health Outcomes Scoring Software was used to generate a Quality of Life analysis dataset based on the SF-36 questionnaire. QoL data were transformed to generate Quality-Adjusted Life Years (QALY) scores. A standard algorithm was developed for processing subjects' answers and producing QALY scores. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Median and range of the change from baseline of the SF-36v2 score are presented for each time point. Analysis was carried out for all subjects regardless of age stratum.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  9. Assessment of Changes From Baseline (Day 0) in the SF-36v2 Daily Questionnaire Subscale Component, Summary Component and QALY Scores for Subjects Who Reported at Least One Local or General Solicited AE Post First Vaccination.

    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). For all subscale component, 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.

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

  10. Assessment of Changes From Baseline (Day 0) for the SF-36v2 Weekly Health 8-score for All Subjects Who Did and Who Did Not Report Any Grade 3 Solicited Symptoms Post Vaccination.

    Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. 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. For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  11. Assessment of Changes From Baseline (Day 0) in the SF-36v2 Weekly Questionnaire General Health Scores(Physical and Mental) for Subjects Who Did and Who Did Not Report Any Grade 3 Solicited Symptoms Post Vaccination.

    Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. The assessed parameters for change from baseline were physical and mental component defined as summary components (PCS and MCS) or general health scores (GHS). For all subscale component, 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. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  12. Assessment of Changes From Baseline (Day 0) for Quality Adjusted Life Years (QALY) Weekly Scores for All Subjects Who Did and Who Did Not Report Any Grade 3 Solicited Symptoms Post Vaccination.

    Median and range of the change from baseline of the SF-36v2 score are presented for each time point. The assessed parameters for change from baseline were QALY scores. For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

    Measured: Day 0 (baseline) and at Days 7 and 21 QoL evaluation (post dose 1) and Day 28 QoL evaluation (post dose 2)

  13. Time Taken to Return to (or go Beyond) the Baseline (Day 0) Value in the SF-36v2 Daily Questionnaire Subscale Component, Summary Component and QALY Scores in Subjects Who Reported Unsolicited AEs Post Vaccination Dose 1

    The assessed parameters 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) and physical and mental component summary measures (PCS, MCS) and QALY for subjects who reported unsolicited AEs in the first 7 days after Dose 1. Only negative deviations from baseline were considered. On any variable, if there was a negative deviation from baseline, then if and only if the value returned to baseline or above within the 7 days after dose 1, the number of days required to return to baseline or above was calculated. On any variable, if there was no variation within the 7 days after dose 1, then nothing was counted. If there was more than one negative deviation from baseline and more than one recovery, then only the first was considered. Analyses by age category were not performed for the daily SF-36v2 questionnaire results.

    Measured: During the 7 days after Dose 1

  14. Quantitative Differences Between SF-36v2 Questionnaire Responses, and the Solicited Local and General Adverse Event Data Provided on Diary Cards

    The analysis of Quantitative differences between SF-36v2 questionnaire responses, and the solicited local and general adverse event data provided on diary cards was invalidated as the differences in scale between the measures could not be reconciled.

    Measured: After the first and second vaccine doses

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2013 (estimated)
  2. Study start22 Mar 2013
  3. Primary completion27 Mar 2014
  4. Study completion25 Feb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01788228
Sponsor's protocol ID
116861
Status last verified
Jun 2020
First submitted
31 Jan 2013
Last updated
23 Jun 2020
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Standaert B, Dort T, Linden J, Madan A, Bart S, Chu L, Hayney MS, Kosinski M, Kroll R, Malak J, Meier G, Segall N, Schuind A. Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study. Health Qual Life Outcomes. 2019 May 6;17(1):80. doi: 10.1186/s12955-019-1147-4.

    PubMed 31060567

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) in people with Influenza and Influenza Vaccines, run by GlaxoSmithKline at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Overall and by Age Category (18-64 and >64 Years of Age). (time frame: During a 7-day follow-up period (Days 0-6) after each vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01788228, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2020.

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