Trial Outcomes & Findings for Comparing Safety and Immunogenicity of HEPLISAV-B® to Engerix-B® in Chronic Kidney Disease (CKD) Patients (NCT NCT00985426)

Last Updated: 2021-05-19

Results Overview

SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit \[mIU\]/mL) after HEPLISAV-B compared to that after Engerix-B.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

521 participants

Primary outcome timeframe

Week 28

Results posted on

2021-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	HEPLISAV-B To mimic the Engerix dosing regimen and to maintain the blind, subjects randomized to the HEPLISAV group received 0.5 mL HEPLISAV and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. To mimic the Engerix dosing regimen and to maintain the blind, subjects also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B Subjects randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Overall Study STARTED	258	263
Overall Study COMPLETED	215	219
Overall Study NOT COMPLETED	43	44

Reasons for withdrawal

Reasons for withdrawal
Measure	HEPLISAV-B To mimic the Engerix dosing regimen and to maintain the blind, subjects randomized to the HEPLISAV group received 0.5 mL HEPLISAV and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. To mimic the Engerix dosing regimen and to maintain the blind, subjects also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B Subjects randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Overall Study Adverse Event	0	1
Overall Study Subject Non-Compliance	3	3
Overall Study Withdrawal by Subject	12	16
Overall Study Lost to Follow-up	8	10
Overall Study Death	7	3
Overall Study Protocol Violation	2	0
Overall Study Lack of seroprotection at protocol-specified timepoints	11	11

Baseline Characteristics

Comparing Safety and Immunogenicity of HEPLISAV-B® to Engerix-B® in Chronic Kidney Disease (CKD) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HEPLISAV-B n=254 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=262 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.	Total n=516 Participants Total of all reporting groups
Age, Continuous	61.4 years STANDARD_DEVIATION 9.1 • n=5 Participants	61.3 years STANDARD_DEVIATION 9.7 • n=7 Participants	61.3 years STANDARD_DEVIATION 9.4 • n=5 Participants
Age, Customized Age Strata · 18 to 39 years	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Age, Customized Age Strata · 40 to 55 years	58 Participants n=5 Participants	52 Participants n=7 Participants	110 Participants n=5 Participants
Age, Customized Age Strata · 56 to 75 years	193 Participants n=5 Participants	199 Participants n=7 Participants	392 Participants n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	104 Participants n=7 Participants	198 Participants n=5 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	158 Participants n=7 Participants	318 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	65 Participants n=5 Participants	71 Participants n=7 Participants	136 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	189 Participants n=5 Participants	191 Participants n=7 Participants	380 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	44 Participants n=5 Participants	47 Participants n=7 Participants	91 Participants n=5 Participants
Race (NIH/OMB) White	204 Participants n=5 Participants	203 Participants n=7 Participants	407 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Body Mass Index	34.05 kg/m2 STANDARD_DEVIATION 8.45 • n=5 Participants	32.15 kg/m2 STANDARD_DEVIATION 6.94 • n=7 Participants	33.09 kg/m2 STANDARD_DEVIATION 7.77 • n=5 Participants
Smoking status Yes	34 Participants n=5 Participants	43 Participants n=7 Participants	77 Participants n=5 Participants
Smoking status No	220 Participants n=5 Participants	219 Participants n=7 Participants	439 Participants n=5 Participants
Glomerular Filtration Rate (GFR) at Screening GFR ≤ 15 mL/min/1.73 m2	39 Participants n=5 Participants	55 Participants n=7 Participants	94 Participants n=5 Participants
Glomerular Filtration Rate (GFR) at Screening GFR 16 - 30 mL/min/1.73 m2	99 Participants n=5 Participants	96 Participants n=7 Participants	195 Participants n=5 Participants
Glomerular Filtration Rate (GFR) at Screening GFR ≥ 31 mL/min/1.73 m2	116 Participants n=5 Participants	111 Participants n=7 Participants	227 Participants n=5 Participants
Screening Creatinine	2.66 mg/dL STANDARD_DEVIATION 1.42 • n=5 Participants	2.82 mg/dL STANDARD_DEVIATION 1.64 • n=7 Participants	2.74 mg/dL STANDARD_DEVIATION 1.53 • n=5 Participants
History of Type 2 Diabetes Mellitus	173 Participants n=5 Participants	161 Participants n=7 Participants	334 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 28

Population: Modified Intent-to-Treat (mITT) population comprises all randomized participants who received at least 1 study injection and had at least 1 post-injection immunogenicity evaluation.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=227 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=242 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response	204 Participants	198 Participants

SECONDARY outcome

Timeframe: 7 days after each injection visit (Weeks 0, 4, 8, and 24)

Population: Safety population includes randomized participants who received at least 1 study injection.

Local reactions include redness greater than or equal to 25 mm, swelling greater than or equal to 25 mm, and pain. Systemic reactions include malaise, headache, myalgia, fatigue, and fever (temperature greater than or equal to 38ºC). This table presents post-injection reactions at active injection visits only. Post-injection reactions after the third (placebo) injection visit in the HEPLISAV-B group are not included.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=254 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=262 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Reactogenicity as Measured by the Percentage of Participants With Local and Systemic Post-injection Reactions Within 7 Days After Each Injection Visit Local reactions	73 Participants	90 Participants
Reactogenicity as Measured by the Percentage of Participants With Local and Systemic Post-injection Reactions Within 7 Days After Each Injection Visit Systemic reactions	85 Participants	91 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Population: Modified Intent-to-Treat (mITT) population comprises all randomized participants who received at least 1 study injection and had at least 1 post-injection immunogenicity evaluation.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=247 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=260 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 24	78.7 percentage of participants (SPR) Interval 72.9 to 83.8	62.2 percentage of participants (SPR) Interval 55.8 to 68.3
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 52	84.3 percentage of participants (SPR) Interval 78.8 to 88.9	77.3 percentage of participants (SPR) Interval 71.2 to 82.6
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 4	5.7 percentage of participants (SPR) Interval 3.1 to 9.3	6.2 percentage of participants (SPR) Interval 3.6 to 9.9
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 8	48.1 percentage of participants (SPR) Interval 41.7 to 54.6	20.2 percentage of participants (SPR) Interval 15.5 to 25.7
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 12	65.1 percentage of participants (SPR) Interval 58.7 to 71.2	50.8 percentage of participants (SPR) Interval 44.4 to 57.2
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 18	73.7 percentage of participants (SPR) Interval 67.6 to 79.2	59.5 percentage of participants (SPR) Interval 53.1 to 65.7
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 28	89.9 percentage of participants (SPR) Interval 85.2 to 93.5	81.8 percentage of participants (SPR) Interval 76.4 to 86.5
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 36	86.9 percentage of participants (SPR) Interval 81.8 to 91.1	80.3 percentage of participants (SPR) Interval 74.7 to 85.2
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 44	83.9 percentage of participants (SPR) Interval 78.4 to 88.6	78.6 percentage of participants (SPR) Interval 72.6 to 83.9

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Population: Modified Intent-to-Treat (mITT) population comprises all randomized participants who received at least 1 study injection and had at least 1 post-injection immunogenicity evaluation.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=247 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=260 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 4	3.6 % participants Interval 1.7 to 6.8	2.7 % participants Interval 1.1 to 5.5
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 24	45.1 % participants Interval 38.6 to 51.7	28.5 % participants Interval 22.9 to 34.5
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 28	73.6 % participants Interval 67.3 to 79.2	63.2 % participants Interval 56.8 to 69.3
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 8	19.5 % participants Interval 14.7 to 25.1	7 % participants Interval 4.2 to 10.8
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 12	27.3 % participants Interval 21.8 to 33.4	22.2 % participants Interval 17.2 to 27.9
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 18	38.6 % participants Interval 32.3 to 45.1	25.9 % participants Interval 20.6 to 31.8
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 36	68.9 % participants Interval 62.4 to 74.9	59 % participants Interval 52.4 to 65.3
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 44	67.9 % participants Interval 61.3 to 74.0	54.5 % participants Interval 47.7 to 61.3
Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 52	66.8 % participants Interval 60.1 to 73.0	49.1 % participants Interval 42.3 to 55.9

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Population: Modified Intent-to-Treat (mITT) population comprises all randomized participants who received at least 1 study injection and had at least 1 post-injection immunogenicity evaluation.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=247 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=260 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 52	170.8 mIU/mL Interval 117.0 to 249.2	51 mIU/mL Interval 34.7 to 74.9
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 4	.4 mIU/mL Interval 0.3 to 0.5	.3 mIU/mL Interval 0.2 to 0.3
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 8	8.1 mIU/mL Interval 5.6 to 11.7	.9 mIU/mL Interval 0.7 to 1.3
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 12	16.5 mIU/mL Interval 11.7 to 23.4	7.2 mIU/mL Interval 5.0 to 10.4
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 18	33 mIU/mL Interval 23.4 to 46.6	12 mIU/mL Interval 8.4 to 17.2
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 24	44.3 mIU/mL Interval 31.6 to 62.3	15.1 mIU/mL Interval 10.6 to 21.5
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 28	587.1 mIU/mL Interval 386.7 to 891.4	156.5 mIU/mL Interval 103.6 to 236.3
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 36	302.3 mIU/mL Interval 200.5 to 456.0	104.2 mIU/mL Interval 69.8 to 155.6
Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 Week 44	214.5 mIU/mL Interval 145.2 to 316.8	71.2 mIU/mL Interval 48.1 to 105.5

SECONDARY outcome

Timeframe: Week 28

Population: Modified Intent-to-Treat (mITT) population comprises all randomized participants who received at least 1 study injection and had at least 1 post-injection immunogenicity evaluation.

Outcome measures

Outcome measures
Measure	HEPLISAV-B n=153 Participants Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=150 Participants Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
SPR of Participants With Type 2 Diabetes Mellitus at Week 28	137 Participants	115 Participants

Adverse Events

HEPLISAV-B

Serious events: 68 serious events

Other events: 140 other events

Deaths: 7 deaths

Engerix-B

Serious events: 76 serious events

Other events: 146 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Robert Janssen MD \ VP & Chief Medical Officer

Dynavax Technologies, Inc.

Phone: 510-665-0414

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	HEPLISAV-B n=254 participants at risk Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=262 participants at risk Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Blood and lymphatic system disorders Anaemia	1.6% 4/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Blood and lymphatic system disorders Coagulopathy	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Blood and lymphatic system disorders Thrombocytopenia	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Acute coronary syndrome	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Acute myocardial infarction	1.2% 3/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.76% 2/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Angina pectoris	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.1% 3/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Angina unstable	0.79% 2/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Atrial fibrillation	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Cardiac arrest	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Cardiac failure	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Cardiac failure congestive	3.1% 8/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Cardio-respiratory arrest	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Coronary artery disease	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.9% 5/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Coronary artery insufficiency	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Myocardial infarction	1.2% 3/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.76% 2/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Cardiac disorders Myocardial ischaemia	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Ear and labyrinth disorders Vertigo	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Ascites	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Diarrhoea	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Enlarged uvula	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Gastric ulcer haemorrhage	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Gastritis erosive	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Haemorrhoids	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Peritonitis	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Retroperitoneal haematoma	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Generalised oedema	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Hernia obstructive	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Medical device complication	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Multi-organ failure	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Non-cardiac chest pain	0.79% 2/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Pyrexia	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Hepatobiliary disorders Cholecystitis	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.76% 2/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Bacterial pyelonephritis	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Catheter site infection	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Cellulitis	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.1% 3/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Cellulitis staphylococcal	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Chronic tonsillitis	0.00% 0/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Clostridium difficile colitis	0.79% 2/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Diabetic foot infection	0.39% 1/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.00% 0/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).

Other adverse events
Measure	HEPLISAV-B n=254 participants at risk Participants randomized to the HEPLISAV-B group received 0.5 mL HEPLISAV-B and 0.5 mL Placebo (saline) via intramuscular (IM) injections at Weeks 0, 4, and 24. Participants also received two 0.5-mL IM injections of Placebo (saline) at Week 8.	Engerix-B n=262 participants at risk Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Blood and lymphatic system disorders Anaemia	3.5% 9/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	4.2% 11/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Eye disorders Cataract	2.8% 7/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.1% 3/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Constipation	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	4.2% 11/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Diarrhoea	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.8% 10/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Nausea	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	5.0% 13/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Gastrointestinal disorders Vomiting	2.4% 6/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Fatigue	6.3% 16/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	5.0% 13/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
General disorders Oedema peripheral	6.3% 16/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	5.0% 13/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Bronchitis	3.5% 9/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Gastroenteritis	2.8% 7/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.76% 2/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Nasopharyngitis	5.1% 13/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	6.9% 18/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Sinusitis	2.8% 7/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Upper respiratory tract infection	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	4.2% 11/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Infections and infestations Urinary tract infection	4.7% 12/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Investigations Blood creatine phosphokinase increased	2.8% 7/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.9% 5/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Gout	2.8% 7/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Hyperkalaemia	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.3% 6/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Hyperphosphataemia	1.6% 4/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Hypoglycaemia	2.4% 6/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.3% 6/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Hypokalaemia	3.5% 9/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	1.5% 4/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Metabolism and nutrition disorders Metabolic acidosis	1.6% 4/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.3% 6/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 15/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Back pain	1.2% 3/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	4.6% 12/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Muscle spasms	2.0% 5/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.8% 10/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.0% 5/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Myalgia	0.79% 2/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.3% 6/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 8/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	4.2% 11/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Nervous system disorders Dizziness	1.6% 4/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Nervous system disorders Headache	3.5% 9/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Psychiatric disorders Insomnia	2.4% 6/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	0.38% 1/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Renal and urinary disorders Renal failure chronic	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	5.0% 13/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Respiratory, thoracic and mediastinal disorders Cough	4.3% 11/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.4% 9/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.1% 8/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.4% 9/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 4/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.3% 6/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Skin and subcutaneous tissue disorders Pruritus	0.79% 2/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	3.1% 8/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Vascular disorders Hypertension	3.1% 8/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	6.9% 18/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).
Vascular disorders Hypotension	2.4% 6/254 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).	2.7% 7/262 • Reporting period for adverse events (AEs) that were not serious adverse events (SAEs) was the time from the first study injection until Week 28. Reporting period for SAEs was the time from the signing of the informed consent form until Week 52 (or completion of the participant's participation in the study).