Trial Outcomes & Findings for Response to the SHINGRIX Varicella Zoster Virus (VZV) Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's Tyrosine Kinase Inhibitor (BTK-I) (NCT NCT03702231)

Last Updated: 2023-08-04

Results Overview

Determine the rate of varicella zoster virus (VZV) seroprotective titer achievement in participants following completion of the SHINGRIX 2-dose vaccine series in Chronic Lymphocytic Leukemia (CLL) patients that are treatment naive or receiving therapy with a Bruton Tyrosine Kinase (BTK) Inhibitor (Ibrutinib or Acalabrutinib). The response criteria for achieving serologic response against VZV following the SHINGRIX vaccine are based on a validated luciferase immunoprecipitation assay detecting VZV antiglycoprotein E antibody. The primary endpoint is serologic response defined as ≥ four-fold rises in VZV anti-gE blood. IgG titer achievement after completing the SHINGRIX (RZV) 2-dose vaccine series.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

116 participants

Primary outcome timeframe

6 months after the first vaccine administration

Results posted on

2023-08-04

Participant Flow

Participant milestones

Participant milestones
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Overall Study STARTED	58	30	28
Overall Study COMPLETED	56	26	24
Overall Study NOT COMPLETED	2	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Overall Study Withdrawal by Subject	1	0	0
Overall Study Protocol Violation	0	0	1
Overall Study Change in CLL Treatment	0	0	1
Overall Study COVID Pandemic	1	4	1
Overall Study Non-compliance	0	0	1

Baseline Characteristics

Response to the SHINGRIX Varicella Zoster Virus (VZV) Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's Tyrosine Kinase Inhibitor (BTK-I)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=58 Participants Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=30 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=28 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Total n=116 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=99 Participants	7 Participants n=107 Participants	16 Participants n=206 Participants	48 Participants n=7 Participants
Age, Categorical >=65 years	33 Participants n=99 Participants	23 Participants n=107 Participants	12 Participants n=206 Participants	68 Participants n=7 Participants
Sex: Female, Male Female	26 Participants n=99 Participants	15 Participants n=107 Participants	8 Participants n=206 Participants	49 Participants n=7 Participants
Sex: Female, Male Male	32 Participants n=99 Participants	15 Participants n=107 Participants	20 Participants n=206 Participants	67 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	4 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=99 Participants	29 Participants n=107 Participants	26 Participants n=206 Participants	110 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	6 Participants n=7 Participants
Race (NIH/OMB) White	55 Participants n=99 Participants	27 Participants n=107 Participants	25 Participants n=206 Participants	107 Participants n=7 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	3 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Region of Enrollment United States	59 participants n=99 Participants	29 participants n=107 Participants	28 participants n=206 Participants	116 participants n=7 Participants

PRIMARY outcome

Timeframe: 6 months after the first vaccine administration

Population: 116 patients enrolled in study and 106 patients were analyzed. 10 patients did not complete study.

Outcome measures

Outcome measures
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=56 Participants Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=26 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=24 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Number of Participants With Varicella Zoster Virus (VZV) Seroprotective Titer	43 Participants	11 Participants	9 Participants

SECONDARY outcome

Timeframe: 6 months after the first vaccine administration

Determine the safety and tolerability of the SHINGRIX vaccine among Chronic Lymphocytic Leukemia (CLL) patients who are treatment naïve or receiving a Brutons-tyrosine kinase inhibitor (BTK-I) (Ibrutinib or Acalabrutinib).

Outcome measures

Outcome measures
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=58 Participants Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=30 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=28 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Number of Participants That Experienced Serious Adverse Events Following the SHINGRIX Vaccine Among Chronic Lymphocytic Leukemia Patients.	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months after the first vaccine administration

Determine the tolerability of the SHINGRIX vaccine among Chronic Lymphocytic Leukemia (CLL) patients who are treatment naïve or receiving a Brutons-tyrosine kinase inhibitor (BTK-I) (Ibrutinib or Acalabrutinib).

Outcome measures

Outcome measures
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=58 Participants Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=30 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=28 Participants Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Number of Participants That Did Not Complete Study Due to Intolerance of the SHINGRIX Vaccine Among Chronic Lymphocytic Leukemia Patients.	0 Participants	0 Participants	0 Participants

Adverse Events

Chronic Lymphocytic Leukemia Patients That Are Treatment Naive

Serious events: 1 serious events

Other events: 58 other events

Deaths: 0 deaths

Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=58 participants at risk Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=30 participants at risk Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=28 participants at risk Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Infections and infestations Lung Infection	1.7% 1/58 • Number of events 1 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/30 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.

Other adverse events

Additional Information

Christopher Pleyer, M.D. Principal Investigator, NIH, NHLBI

National Institutes of Health (NIH) / The National Heart, Lung, and Blood Institute (NHLBI)

Phone: 510.709.6649

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Chronic Lymphocytic Leukemia Patients That Are Treatment Naive n=58 participants at risk Chronic Lymphocytic Leukemia Patients That Are Treatment Naive will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib n=30 participants at risk Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib n=28 participants at risk Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib will be followed for 6 months and receive assessment of serologic response 6- months following the first SHINGRIX vaccine dose. Zoster Vaccine Recombinant, Adjuvanted: A series of 2 doses of SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) will be given on a 0- and 3-month schedule by intramuscular injection.
Gastrointestinal disorders Nausea	17.2% 10/58 • Number of events 11 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	23.3% 7/30 • Number of events 8 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Chills	22.4% 13/58 • Number of events 17 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	20.0% 6/30 • Number of events 9 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	14.3% 4/28 • Number of events 4 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Edema limbs	5.2% 3/58 • Number of events 4 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	3.3% 1/30 • Number of events 1 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	3.6% 1/28 • Number of events 1 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Fatigue	53.4% 31/58 • Number of events 51 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	40.0% 12/30 • Number of events 22 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	53.6% 15/28 • Number of events 31 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Flu like symptoms	37.9% 22/58 • Number of events 36 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	13.3% 4/30 • Number of events 5 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	32.1% 9/28 • Number of events 12 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Injection site reaction	81.0% 47/58 • Number of events 103 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	66.7% 20/30 • Number of events 39 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	53.6% 15/28 • Number of events 28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Pain	100.0% 58/58 • Number of events 191 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	93.3% 28/30 • Number of events 66 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	96.4% 27/28 • Number of events 72 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Nervous system disorders Headache	63.8% 37/58 • Number of events 61 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	43.3% 13/30 • Number of events 19 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	32.1% 9/28 • Number of events 13 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Fever	10.3% 6/58 • Number of events 6 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	6.7% 2/30 • Number of events 2 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Headache	1.7% 1/58 • Number of events 1 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	6.7% 2/30 • Number of events 2 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Myalgia	1.7% 1/58 • Number of events 2 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	10.0% 3/30 • Number of events 7 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Vaccination complication	3.4% 2/58 • Number of events 3 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	10.0% 3/30 • Number of events 5 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Vaccination site lymphadenopathy	12.1% 7/58 • Number of events 9 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	6.7% 2/30 • Number of events 2 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Musculoskeletal and connective tissue disorders Myalgia	56.9% 33/58 • Number of events 57 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	36.7% 11/30 • Number of events 24 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	46.4% 13/28 • Number of events 24 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Nervous system disorders Dizziness	5.2% 3/58 • Number of events 4 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	6.7% 2/30 • Number of events 3 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Skin and subcutaneous tissue disorders Rash maculo-papular	12.1% 7/58 • Number of events 8 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	10.0% 3/30 • Number of events 5 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/28 • Events will be collected for 7 days following the first and second vaccine dose All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.