The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: GlaxoSmithKline (GSK) Biologicals H5N1 Pandemic Influenza Vaccine (GSK 1557484A) Study Number: 116861 (FLU Q-PAN-022) Title: Safety and tolerability of GSK 1557484A vaccine in adults at occupational risk for influenza A (H5N1) exposure. GSK 1557484A (H5N1): GlaxoSmithKline (GSK) Biologicals adjuvanted A/Indonesia/5/2005 (H5N1) vaccine. Rationale: The purpose of this study was to assess the safety and tolerability of H5N1 vaccine in an adult population at occupational risk for influenza A (H5N1) exposure. This CTRS presents data up to Day 51. The study is ongoing and the CTRS will be updated with results from later timepoint(s) once the data is available. Phase: III Study Period:22 March 2013 to 07 April 2014 (Day 51) Study Design: Open-label, multi-center, single country, single group study. Centres: 6 centers in United States Indication: Immunization of adults 18 years of age and older against H5N1 influenza. Treatment: The study groups were as follows: H5N1 Group: Subjects received 2 doses of H5N1 vaccine at Days 0 and 21. For some pre-specified analyses, subjects were categorized by age groups as: H5N1 Adults Group: Subjects aged 18-64 years received 2 doses of H5N1 vaccine at Days 0 and 21. H5N1 Elderly Group: Subjects aged >64 years received 2 doses of H5N1 vaccine at Days 0 and 21. The vaccine was administered intramuscularly in the deltoid region of arm (Non-dominant arm at Day 0 and Dominant arm at Day 21). Objectives: To describe the safety of H5N1 vaccine in terms of solicited local and general adverse events for 7 days and all unsolicited AEs for 21 days after each vaccination. Primary Outcome Variable(s): Solicited local and general symptoms overall and by age category (18-64 and >64 years of age) Occurrence of each solicited local symptom during a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccination Occurrence and relationship to vaccination of each solicited general symptom during a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccination Unsolicited adverse events overall and by age category (18-64 and >64 years of age): Occurrence and relationship to vaccination* of unsolicited adverse events (AEs) within 21 days after each dose. *At the time of writing this CTRS, result of this outcome was not available. The CTRS will be updated when this results become available Secondary Outcome Variable(s)*: Quality of life measures as assessed overall and by age category (18-64 and >64 years of age): Change from baseline in the daily SF-36v2 scores (subscale component scores, summary scores and utility scores) by solicited local and general adverse event status after the first vaccine dose Change from baseline (as collected by both the SF-36v2 daily and weekly questionnaires) in the following parameters: Physical functioning Physical-health related role limitations Bodily pain General health Vitality Social functioning Emotional health related role limitations Mental health Change from baseline in physical and mental component summary measures based on the data collected in both daily and weekly SF-36v2 questionnaires
Change from baseline in SF-6D utility measures based on the data collected in both daily and weekly SF-36v2 questionnaires Change from baseline in the weekly SF-36v2 scores (subscale component scores, summary scores and utility scores) by solicited local and general adverse event status after the first and second vaccine doses In the case of an adverse event report during the 7 days after dose 1, time to return to baseline in the daily and weekly SF36v2 scores To concurrently assess psychometric validity and internal consistency of the daily SF-36v2 questionnaire, the following additional endpoints will be assessed: Quantitative differences between SF-36v2 questionnaire responses, and the solicited local and general adverse event data provided on diary cards. Occurrence and relationship to vaccination of Medically Attended Adverse Events (MAEs)**, Potential Immune- Mediated Diseases (pimds), Serious Adverse Events (SAEs) and adverse pregnancy outcomes** during the entire study period. *This summary contains only safety data until Day 51 of this study. It will be updated when results for other outcome variables become available. **At the time of writing this CTRS, result of these outcomes were not available. The CTRS will be updated when this result become available Statistical Methods: The analyses were performed on the Total Vaccinated cohort. - The Total Vaccinated cohort included all vaccinated subjects for whom safety data were available. Analysis of Safety : The analysis was performed on the Total Vaccinated cohort. The percentages of subjects reporting each individual solicited local and general AEs during a 7-day (Days 0-6) follow-up period after each vaccination and across doses were tabulated with exact 95%CI. The same tabulation was performed for grade 3 solicited AEs and for solicited general AEs assessed by the investigators as causally related to vaccination. The percentage of subjects with at least one report of an unsolicited AEs, classified by the Medical Dictionary for Regulatory Activities (MedDRA) preferred term, during the 21-day (Days 0-20) follow-up period after each vaccination was tabulated for the treatment group. The percentages of subjects reporting SAEs and pimds, according to MedDRA preferred terms were tabulated up to Day 51. SAEs and pimds classified according to MedDRA preferred terms and assessed by the investigators to be causally related to vaccination were also reported. Study Population: Healthy male and female adults 18 years of age at time of first study vaccination and who were 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; were included in this study. Female subjects of childbearing potential had to practice adequate contraception for 30 days prior to vaccination, to have a negative pregnancy test on the day of first vaccination and had agreed to continue adequate contraception during the entire treatment period for 2 months after completion of the vaccination series. Subjects with significant risk of complications from intramuscular injections due to disorder of coagulation were excluded from this study. Written informed consent was obtained from the subjects prior to study entry. Number of Subjects H5N1 Adults Group H5N1 Elderly Group H5N1 Group Planned, N Not Applicable Not Applicable 150 Randomised, N (Total Vaccinated cohort) 49 1 50 Completed, n (%) Day 51 48 (98.0) 1 (100) 49 (98.0) Total Number Subjects Withdrawn, n (%) 1 (2.0) 0 (0.0) 1 (2.0) Withdrawn due to Adverse Events n (%) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy n (%) Not Applicable Not Applicable Not Applicable Withdrawn for other reasons n (%) 1 (2.0) 0 (0.0) 1 (2.0) Demographics H5N1 Adults Group H5N1 Elderly Group H5N1 Group N (Total Vaccinated Cohort) 49 1 50 Females, n (%) 28 (57.1) 0 (0.0) 28 (56.0) Males, n (%) 21 (42.9) 1 (100) 22 (44.0) Mean Age, years (SD) 42.5 (10.7) 85.0 (Not Applicable*) 43.3 (12.2) Median Age, years (minimum, maximum) 41 (26, 62) 85 (85, 85) 42 (26, 85) White - Caucasian / European Heritage, n (%) 33 (67.3) 1 (100) 34 (68.0) African Heritage / African American, n (%) 3 (6.1) 0 (0.0) 3 (6.0) Asian - East Asian Heritage, n (%) 3 (6.1) 0 (0.0) 3 (6.0)
Asian - Japanese Heritage, n (%) 3 (6.1) 0 (0.0) 3 (6.0) Asian - South East Asian Heritage, n (%) 3 (6.1) 0 (0.0) 3 (6.0) *as this group has only 1 subject, SD cannot be calculated. Primary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 7-day (Days 0-6) postvaccination period following each dose and across doses (Total Vaccinated cohort) H5N1 Adults Group H5N1 Elderly Group H5N1 Group 95 % CI 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL N n % LL UL Dose 1 Pain Any 49 42 85.7 72.8 94.1 1 1 100 2.5 100 50 43 86.0 73.3 94.2 Grade 3 49 3 6.1 1.3 16.9 1 0 0.0 0.0 97.5 50 3 6.0 1.3 16.5 Redness Any 49 4 8.2 2.3 19.6 1 0 0.0 0.0 97.5 50 4 8.0 2.2 19.2 Swelling Any 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 Dose 2 Pain Any 49 39 79.6 65.7 89.8 1 1 100 2.5 100 50 40 80.0 66.3 90.0 Grade 3 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Redness Any 49 3 6.1 1.3 16.9 1 0 0.0 0.0 97.5 50 3 6.0 1.3 16.5 Swelling Any 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Across doses Pain Any 49 45 91.8 80.4 97.7 1 1 100 2.5 100 50 46 92.0 80.8 97.8 Grade 3 49 4 8.2 2.3 19.6 1 0 0.0 0.0 97.5 50 4 8.0 2.2 19.2 Redness Any 49 6 12.2 4.6 24.8 1 0 0.0 0.0 97.5 50 6 12.0 4.5 24.3 Swelling Any 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 N = number of subjects with at least one documented dose; n/% = number/percentage of subjects reporting the symptom at least once 95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any local symptom regardless of their intensity grade Grade 3 pain = Significant pain at rest. Prevents normal every day activities Primary Outcome Results: Number (%) of subjects reporting solicited general symptoms during the 7-day (Days 0-6) postvaccination period following each dose and across doses (Total Vaccinated cohort) H5N1 Adults Group H5N1 Elderly H5N1 Group Group 95 % CI 95 % CI 95 % CI Symptom Intensity/Relationship N n % LL UL N n % LL UL N n % LL UL Dose 1 Fatigue Any 49 17 34.7 21.7 49.6 1 0 0.0 0.0 97.5 50 17 34.0 21.2 48.8 Related 49 16 32.7 19.9 47.5 1 0 0.0 0.0 97.5 50 16 32.0 19.5 46.7 Gastrointestinal Any 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 Related 49 5 10.2 3.4 22.2 1 0 0.0 0.0 97.5 50 5 10.0 3.3 21.8 Headache Any 49 16 32.7 19.9 47.5 1 0 0.0 0.0 97.5 50 16 32.0 19.5 46.7 Related 49 12 24.5 13.3 38.9 1 0 0.0 0.0 97.5 50 12 24.0 13.1 38.2 Joint pain Any 49 9 18.4 8.8 32.0 1 0 0.0 0.0 97.5 50 9 18.0 8.6 31.4 Related 49 8 16.3 7.3 29.7 1 0 0.0 0.0 97.5 50 8 16.0 7.2 29.1 Muscle ache Any 49 24 49.0 34.4 63.7 1 0 0.0 0.0 97.5 50 24 48.0 33.7 62.6 Related 49 23 46.9 32.5 61.7 1 0 0.0 0.0 97.5 50 23 46.0 31.8 60.7
Shivering (chills) Any 49 3 6.1 1.3 16.9 1 0 0.0 0.0 97.5 50 3 6.0 1.3 16.5 Related 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Sweating Any 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Related 49 1 2.0 0.1 10.9 1 0 0.0 0.0 97.5 50 1 2.0 0.1 10.6 Temperature/(Oral) 38.0 C 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 39.0 C 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Related 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Dose 2 Fatigue Any 49 20 40.8 27.0 55.8 1 0 0.0 0.0 97.5 50 20 40.0 26.4 54.8 Related 49 19 38.8 25.2 53.8 1 0 0.0 0.0 97.5 50 19 38.0 24.7 52.8 Gastrointestinal Any 49 5 10.2 3.4 22.2 1 0 0.0 0.0 97.5 50 5 10.0 3.3 21.8 Related 49 3 6.1 1.3 16.9 1 0 0.0 0.0 97.5 50 3 6.0 1.3 16.5 Headache Any 49 15 30.6 18.3 45.4 1 0 0.0 0.0 97.5 50 15 30.0 17.9 44.6 Related 49 14 28.6 16.6 43.3 1 0 0.0 0.0 97.5 50 14 28.0 16.2 42.5 Joint pain Any 49 11 22.4 11.8 36.6 1 0 0.0 0.0 97.5 50 11 22.0 11.5 36.0 Related 49 10 20.4 10.2 34.3 1 0 0.0 0.0 97.5 50 10 20.0 10.0 33.7 Muscle ache Any 49 22 44.9 30.7 59.8 1 0 0.0 0.0 97.5 50 22 44.0 30.0 58.7 Related 49 21 42.9 28.8 57.8 1 0 0.0 0.0 97.5 50 21 42.0 28.2 56.8 Shivering (chills) Any 49 8 16.3 7.3 29.7 1 0 0.0 0.0 97.5 50 8 16.0 7.2 29.1 Grade 3 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Related 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 Sweating Any 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 Grade 3 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Related 49 5 10.2 3.4 22.2 1 0 0.0 0.0 97.5 50 5 10.0 3.3 21.8 Temperature/(Oral) 38.0 C 49 1 2.0 0.1 10.9 1 0 0.0 0.0 97.5 50 1 2.0 0.1 10.6 39.0 C 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Related 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Across doses Fatigue Any 49 27 55.1 40.2 69.3 1 0 0.0 0.0 97.5 50 27 54.0 39.3 68.2 Related 49 26 53.1 38.3 67.5 1 0 0.0 0.0 97.5 50 26 52.0 37.4 66.3 Gastrointestinal Any 49 12 24.5 13.3 38.9 1 0 0.0 0.0 97.5 50 12 24.0 13.1 38.2 Grade 3 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Related 49 8 16.3 7.3 29.7 1 0 0.0 0.0 97.5 50 8 16.0 7.2 29.1 Headache Any 49 20 40.8 27.0 55.8 1 0 0.0 0.0 97.5 50 20 40.0 26.4 54.8 Grade 3 49 2 4.1 0.5 14.0 1 0 0.0 0.0 97.5 50 2 4.0 0.5 13.7 Related 49 17 34.7 21.7 49.6 1 0 0.0 0.0 97.5 50 17 34.0 21.2 48.8 Joint pain Any 49 14 28.6 16.6 43.3 1 0 0.0 0.0 97.5 50 14 28.0 16.2 42.5 Related 49 13 26.5 14.9 41.1 1 0 0.0 0.0 97.5 50 13 26.0 14.6 40.3 Muscle ache Any 49 33 67.3 52.5 80.1 1 0 0.0 0.0 97.5 50 33 66.0 51.2 78.8 Related 49 31 63.3 48.3 76.6 1 0 0.0 0.0 97.5 50 31 62.0 47.2 75.3 Shivering (chills) Any 49 10 20.4 10.2 34.3 1 0 0.0 0.0 97.5 50 10 20.0 10.0 33.7 Related 49 8 16.3 7.3 29.7 1 0 0.0 0.0 97.5 50 8 16.0 7.2 29.1 Sweating Any 49 7 14.3 5.9 27.2 1 0 0.0 0.0 97.5 50 7 14.0 5.8 26.7 Related 49 5 10.2 3.4 22.2 1 0 0.0 0.0 97.5 50 5 10.0 3.3 21.8
Temperature/(Oral) 38.0 C 49 1 2.0 0.1 10.9 1 0 0.0 0.0 97.5 50 1 2.0 0.1 10.6 39.0 C 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 Related 49 0 0.0 0.0 7.3 1 0 0.0 0.0 97.5 50 0 0.0 0.0 7.1 N = number of subjects with at least one documented dose; n/% = number/percentage of subjects reporting the symptom at least once 95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any general symptom regardless of their intensity grade or relationship to vaccination Grade 3 symptom = symptom that prevented normal activity Related = symptom assessed by the investigator as causally related to the study vaccination Secondary Outcome Variable(s): Number (%) of subjects with pimds up to Day 51 (Total Vaccinated cohort) All pimds H5N1 Adults Group H5N1 Elderly Group Subjects with any pimd(s), n (%) 0 (0.0) 0 (0.0) Subjects with related pimd(s), n (%) 0 (0.0) 0 (0.0) Safety Results: Number (%) of subjects with unsolicited AEs reported during the 21 day (Days 0-20 post dose 1 and Days 21-41 post dose 2) post vaccination period (Total Vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within days 0-20 and days 21-41 following vaccination) H5N1 Adults Group H5N1 Elderly Group Subjects with any AE(s), n (%) 10 (20.4) 0 (0.0) Acute sinusitis 1 (2.0) - Axillary pain 1 (2.0) - Cough 1 (2.0) - Dermatitis allergic 1 (2.0) - Epistaxis 1 (2.0) - Gastrointestinal disorder 1 (2.0) - Injection site pruritus 1 (2.0) - Intervertebral disc degeneration 1 (2.0) - Labile hypertension 1 (2.0) - Lymphadenopathy 1 (2.0) - Menstruation irregular 1 (2.0) - Oropharyngeal pain 1 (2.0) - Pain in jaw 1 (2.0) - Rectal haemorrhage 1 (2.0) - Upper respiratory tract infection 1 (2.0) - -: Adverse event absent Safety Results: Number (%) of subjects with serious adverse events reported up to Day 51 (Total Vaccinated cohort) All SAEs Subjects with any SAE(s), n (%) [n assessed by the investigator as related] Fatal SAEs Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related] H5N1 Adults Group H5N1 Elderly Group 0 (0.0) [0] 0 (0.0) [0] H5N1 Adults Group H5N1 Elderly Group 0 (0.0) [0] 0 (0.0) [0] Conclusion: During the 7-day (Days 0-6) post-vaccination period, pain was reported for 45 (91.8%) subjects in H5N1 Adults Group and 1 (100%) subject in H5N1 Elderly Group; redness and swelling was reported for 6 (12.2%) and 7(14.3%) subjects respectively, in H5N1 Adults Group. No redness and swelling was reported in H5N1 Elderly Group. During the 7-day (Days 0-6) post-vaccination period, fatigue was reported for 27 (55.1%) subjects, gastrointestinal was reported for 12 (24.5%) subjects, headache was reported for 20 (40.8%) subjects, joint pain was reported for 14 (28.6%) subjects, muscle ache was reported for 33 (67.3%) subjects, shivering (chills) was reported for 10 (20.4%) subjects, sweating was reported for 7 (14.3%) subjects and fever was reported for 1 (2.0%) subject in the H5N1 Adults Group. No
solicited general symptoms were reported in the H5N1 Elderly Group. Muscle ache was considered to be causally related to the vaccination in 31 (62.0%) subjects in H5N1 Adults Group. During the 21 day post vaccination period, at least one unsolicited AE was reported for 10 (20.0%) subjects in H5N1 Adults Group and none in H5N1 Elderly Group. No serious adverse events were reported up to Day 51. Date updated: 09-April-2015