Trial Outcomes & Findings for Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults (NCT NCT01776541)

Last Updated: 2015-02-03

Results Overview

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

979 participants

Primary outcome timeframe

Three weeks after 2nd vaccination (day 43)

Results posted on

2015-02-03

Participant Flow

Subjects were enrolled at 4 centers in the US, 3 centers in Australia and 1 center in Thailand.

All enrolled subjects were included in the trial.

Participant milestones

Participant milestones
Measure	High Dose Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Study STARTED	488	491
Overall Study COMPLETED	432	416
Overall Study NOT COMPLETED	56	75

Reasons for withdrawal

Reasons for withdrawal
Measure	High Dose Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Study Administrative Reason	6	2
Overall Study Death	4	0
Overall Study Lost to Follow-up	27	48
Overall Study Unclassified	5	4
Overall Study Protocol Violation	2	1
Overall Study Withdrawal by Subject	12	20

Baseline Characteristics

Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High Dose n=488 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=491 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Total n=979 Participants Total of all reporting groups
Age, Continuous	39.0 years STANDARD_DEVIATION 13.7 • n=5 Participants	38.4 years STANDARD_DEVIATION 14.2 • n=7 Participants	38.7 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	285 Participants n=5 Participants	259 Participants n=7 Participants	544 Participants n=5 Participants
Sex: Female, Male Male	203 Participants n=5 Participants	232 Participants n=7 Participants	435 Participants n=5 Participants

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done on the Full Analysis Set (FAS) i.e., the subjects who actually receive at least one dose of study vaccination and provide at least one evaluable serum sample both before (baseline) and after vaccination.

Outcome measures

Outcome measures
Measure	High Dose n=478 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=483 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. Day 1	4 Percentages of subjects Interval 3.0 to 6.0	4 Percentages of subjects Interval 2.0 to 6.0
Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. Day 43 (N=451,440)	85 Percentages of subjects Interval 81.0 to 88.0	63 Percentages of subjects Interval 58.0 to 68.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: This analysis was done on the FAS population.

Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Outcome measures

Outcome measures
Measure	High Dose n=451 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=440 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.	83 Percentages of subjects Interval 79.0 to 86.0	61 Percentages of subjects Interval 56.0 to 66.0

PRIMARY outcome

Timeframe: From day 1 through day 7 after any vaccination.

Population: Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.

Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.

Outcome measures

Outcome measures
Measure	High Dose n=473 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=471 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Fever (≥38°C)(N=472,469)	11 Number of subjects	9 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Any Local	322 Number of subjects	236 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Injection site Erythema(N=471,471)	4 Number of subjects	0 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Injection site Induration(N=471,471)	54 Number of subjects	35 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Injection site Ecchymosis(N=472,471)	9 Number of subjects	6 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Injection site Pain(N=471,470)	318 Number of subjects	235 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Any Systemic	223 Number of subjects	209 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Nausea(N=472,471)	54 Number of subjects	48 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Myalgia(N=472,469)	108 Number of subjects	78 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Arthralgia(N=471,467)	70 Number of subjects	52 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Headache(N=471,469)	126 Number of subjects	114 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Fatigue(N=471,469)	125 Number of subjects	108 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Loss of Appetite(N=472,469)	53 Number of subjects	38 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Malaise(N=472,467)	117 Number of subjects	97 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Treatment of pain and (or) fever(N=471,470)	40 Number of subjects	31 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Prevention of pain and (or) fever(N=471,470)	7 Number of subjects	14 Number of subjects
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. Fever (≥40°C)(N=472,469)	1 Number of subjects	0 Number of subjects

PRIMARY outcome

Timeframe: Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387

Population: Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.

Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.

Outcome measures

Outcome measures
Measure	High Dose n=476 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=475 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. Any AEs	94 Number of subjects	92 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. At least possibly related AEs	39 Number of subjects	31 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. Any SAEs	20 Number of subjects	8 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. Deaths	4 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. Medically attended AEs	171 Number of subjects	153 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. AEs resulting in premature withdrawal from study	4 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. AEs of Special Interest	1 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited AEs After Any Vaccination. AEs leading to New Onset of Chronic Disease	11 Number of subjects	14 Number of subjects

SECONDARY outcome

Timeframe: Day 1; day 22; day 43 and day 387

Population: Analysis was done on the FAS set.

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5 for subjects 18-60 years of age.

Outcome measures

Outcome measures
Measure	High Dose n=464 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=461 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. Day22/Day1	5.37 Ratio Interval 4.6 to 6.27	2.43 Ratio Interval 2.07 to 2.84
Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. Day43/Day1 (N=451,440)	41 Ratio Interval 34.0 to 49.0	11 Ratio Interval 8.68 to 13.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. Day387/Day1 (N=411,395)	1.95 Ratio Interval 1.73 to 2.19	1.24 Ratio Interval 1.1 to 1.4

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387

Population: Analysis was done on the FAS set.

Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%.

Outcome measures

Outcome measures
Measure	High Dose n=478 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=483 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. Day 1	4 Percentages of subjects Interval 3.0 to 6.0	4 Percentages of subjects Interval 2.0 to 6.0
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. Day 43 (N=451,440)	85 Percentages of subjects Interval 81.0 to 88.0	63 Percentages of subjects Interval 58.0 to 68.0
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. Day 22 (N=464,461)	52 Percentages of subjects Interval 47.0 to 56.0	30 Percentages of subjects Interval 26.0 to 35.0
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. Day 387 (N=411,395)	27 Percentages of subjects Interval 22.0 to 31.0	11 Percentages of subjects Interval 8.0 to 15.0

SECONDARY outcome

Timeframe: Day 22, day 43 and day 387

Population: Analysis was done on the FAS set.

Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%.

Outcome measures

Outcome measures
Measure	High Dose n=464 Participants Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.	Low Dose n=461 Participants Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. Day 22	48 Percentages of subjects Interval 44.0 to 53.0	27 Percentages of subjects Interval 23.0 to 31.0
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. Day 43 (N=451,440)	83 Percentages of subjects Interval 71.0 to 91.0	61 Percentages of subjects Interval 45.0 to 75.0
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. Day 387 (N=411,395)	22 Percentages of subjects Interval 18.0 to 26.0	9 Percentages of subjects Interval 6.0 to 12.0

Adverse Events

High Dose

Serious events: 20 serious events

Other events: 371 other events

Deaths: 0 deaths

Low Dose

Serious events: 8 serious events

Other events: 324 other events

Deaths: 0 deaths

Total

Serious events: 28 serious events

Other events: 695 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	High Dose n=485 participants at risk Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=490 participants at risk Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Total n=975 participants at risk Total of high dose and low dose groups.
Gastrointestinal disorders NAUSEA	12.0% 58/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	10.4% 51/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	11.2% 109/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders FATIGUE	25.8% 125/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	22.7% 111/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	24.2% 236/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders INJECTION SITE ERYTHEMA	15.7% 76/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	12.4% 61/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	14.1% 137/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders INJECTION SITE HAEMORRHAGE	8.7% 42/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	5.7% 28/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	7.2% 70/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders INJECTION SITE INDURATION	12.2% 59/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	8.4% 41/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	10.3% 100/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders INJECTION SITE PAIN	65.8% 319/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	49.8% 244/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	57.7% 563/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
General disorders MALAISE	24.1% 117/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	19.8% 97/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	21.9% 214/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	10.9% 53/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	9.0% 44/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	9.9% 97/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
Metabolism and nutrition disorders DECREASED APPETITE	11.5% 56/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	7.8% 38/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	9.6% 94/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
Musculoskeletal and connective tissue disorders ARTHRALGIA	15.5% 75/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	12.2% 60/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	13.8% 135/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
Musculoskeletal and connective tissue disorders MYALGIA	23.1% 112/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	16.7% 82/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	19.9% 194/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
Nervous system disorders HEADACHE	27.6% 134/485 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	24.5% 120/490 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.	26.2% 255/975 • Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. Subjects who did not provide unsolicited safety data were excluded from safety evaluation.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place