Trial Outcomes & Findings for Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis (NCT NCT01967134)

NCT ID: NCT01967134

Last Updated: 2019-08-21

Results Overview

Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Through Study Day 210

Results posted on

2019-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	H56:IC31 (50 ug H56) LTBI Neg LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Overall Study STARTED	8	8	9
Overall Study COMPLETED	8	7	9
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	H56:IC31 (50 ug H56) LTBI Neg LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Overall Study Lost to Follow-up	0	1	0

Baseline Characteristics

Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Through Study Day 210

Population: Safety population

Outcome measures

Outcome measures
Measure	H56:IC31 (50 ug H56) LTBI Neg n=8 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=8 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=9 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Number of Participants With at Least One Adverse Event (AE) Through Day 210 Participants with at least one AE after 3rd dose	6 Participants	7 Participants	4 Participants
Number of Participants With at Least One Adverse Event (AE) Through Day 210 Participants with at least one AE after any dose	8 Participants	8 Participants	9 Participants

SECONDARY outcome

Timeframe: Study Day 70

Population: All vaccinated subjects

Whole blood ICS Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response Antigen: Ag85B Cytokine(s): G+2+17+T+ %CD4+ T Cell Response

Outcome measures

Outcome measures
Measure	H56:IC31 (50 ug H56) LTBI Neg n=8 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=8 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=9 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations	0.0008 % change from pre-vacc to day 70 Interval -0.0002 to 0.0026	0.0050 % change from pre-vacc to day 70 Interval 0.0016 to 0.0075	0.0019 % change from pre-vacc to day 70 Interval 0.0011 to 0.0044

SECONDARY outcome

Timeframe: Study Day 70

Population: All vaccinated subjects

Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response 12-Hour Whole Blood Intracellular Cytokine Staining (ICS) Assay Antigen: ESAT6 Cytokine(s): G+2+17+T+ %CD4+ T Cell Response

Outcome measures

Outcome measures
Measure	H56:IC31 (50 ug H56) LTBI Neg n=8 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=8 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=9 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations	0.0000 % change from pre-vacc to day 70 Interval 0.0 to -0.0003	0.0005 % change from pre-vacc to day 70 Interval 0.0001 to 0.0009	0.0005 % change from pre-vacc to day 70 Interval 0.0 to 0.0012

SECONDARY outcome

Timeframe: Study Day 210

Population: All vaccinated subjects

Measure of Mtb positivity by QuantiFERON-TB Gold In-Tube Number of Positive Responses and Shift from Screening to Study Day 210 Post-Vaccination Responses

Outcome measures

Outcome measures
Measure	H56:IC31 (50 ug H56) LTBI Neg n=8 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=8 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=9 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210	2 Participants	6 Participants	9 Participants

SECONDARY outcome

Timeframe: Study Day 210

Population: Subjects in all vaccinated population with available data

Responses to vaccine antigen Ag85B measure by Interferon gamma (IFN-γ) ELISpot assay Unstimulated-subtracted IFN-γ ELISpot Response (Spot forming units/10\^6 PBMC) Antigen: Ag85B

Outcome measures

Outcome measures
Measure	H56:IC31 (50 ug H56) LTBI Neg n=7 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=1 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=7 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210	36.6667 percent change Interval -4.9916 to 83.0868	-8.3333 percent change n=1	80.0000 percent change Interval 11.6905 to 164.9762

Adverse Events

Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Dereck Tait

IAVI

Phone: 27214424991

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	H56:IC31 (50 ug H56) LTBI Neg n=8 Participants LTBI Negative 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (15 ug H56) LTBI Pos n=8 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	H56:IC31 (50 ug H56) LTBI Pos n=9 Participants LTBI Positive 3 Doses H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	20 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment South Africa	8 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants	25 participants n=4 Participants

Measure	Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative n=8 participants at risk LTBI Negative 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive n=8 participants at risk LTBI Positive 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.	Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive n=9 participants at risk LTBI Positive 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
Cardiac disorders Bradycardia	50.0% 4/8 • Number of events 5 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Gastrointestinal disorders Dyspepsia	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Gastrointestinal disorders Nausea	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 7 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Chills	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Fatigue	37.5% 3/8 • Number of events 9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	50.0% 4/8 • Number of events 8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 3 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Injection site erythema	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Injection site pain	62.5% 5/8 • Number of events 12 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	87.5% 7/8 • Number of events 18 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	66.7% 6/9 • Number of events 11 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Injection site pruritus	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Injection site swelling	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	44.4% 4/9 • Number of events 5 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Injection site warmth	62.5% 5/8 • Number of events 9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	75.0% 6/8 • Number of events 10 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	66.7% 6/9 • Number of events 10 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
General disorders Pyrexia	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Immune system disorders Seasonal allergy	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Infections and infestations Bronchitis	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Infections and infestations Rhinitis	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 3 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Infections and infestations Sinusitis	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Infections and infestations Upper respiratory tract infection	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	62.5% 5/8 • Number of events 5 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Injury, poisoning and procedural complications Muscle strain	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Alanine aminotransferase increased	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 3 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Aspartate aminotransferase increased	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Haemoglobin decreased	12.5% 1/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Neutrophil count decreased	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Protein urine	62.5% 5/8 • Number of events 6 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations Red blood cells urine	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	22.2% 2/9 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Investigations White blood cell count increased	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	37.5% 3/8 • Number of events 4 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Joint stiffness	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Myalgia	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 7 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 4 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Nervous system disorders Dizziness	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Nervous system disorders Headache	37.5% 3/8 • Number of events 10 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 5 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	33.3% 3/9 • Number of events 4 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Nervous system disorders Hypoaesthesia	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 2 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Vascular disorders Hot flush	12.5% 1/8 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/8 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	0.00% 0/9 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Vascular disorders Hypertension	25.0% 2/8 • Number of events 4 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	25.0% 2/8 • Number of events 3 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210	11.1% 1/9 • Number of events 1 • Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210