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

• Sponsor: Dynavax Technologies Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00985426
• Collaborator: (none)
• Enrollment: 521
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 18.6

Study Details

Study Description

Brief Summary

The purpose of the study is to demonstrate the safety and immunogenicity of a new investigational hepatitis B virus vaccine, HEPLISAV-B, in patients 18 to 75 years of age who have progressive loss of kidney function.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Biological: HEPLISAV-B; Biological: Engerix-B; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 521 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: An Observer-Blinded, Randomized Study Comparing the Safety and Immunogenicity of HEPLISAV-B® to Licensed Vaccine (Engerix-B®) Among Adults(18 to 75 Years of Age) With Chronic Kidney Disease (CKD)
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HEPLISAV-B 0.5 mL HEPLISAV-B and 0.5 mL Placebo	Biological: HEPLISAV-B; Intramuscular (IM) injections of HEPLISAV-B at Weeks 0, 4, and 24; Other Names: Hepatitis B vaccine (recombinant), adjuvanted ; Other: Placebo; Placebo(saline) intramuscular (IM) injection at Week 8; Other Names: Saline
Active Comparator: Engerix-B 2.0 mL Engerix-B	Biological: Engerix-B; Intramuscular (IM) injections at Weeks 0, 4, 8, and 24; Other Names: Hepatitis B vaccine (recombinant)

Outcome Measures

Primary Outcome Measures

1. Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response [Week 28]

   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.

Secondary Outcome Measures

1. Reactogenicity as Measured by the Percentage of Participants With Local and Systemic Post-injection Reactions Within 7 Days After Each Injection Visit [7 days after each injection visit (Weeks 0, 4, 8, and 24)]

   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.

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 [Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52]

   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.

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 [Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52]

4. Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 [Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52]

5. SPR of Participants With Type 2 Diabetes Mellitus at Week 28 [Week 28]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• be 18 to 75 years of age;

• progressive loss of renal function as defined by glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m²;

• be clinically stable in the opinion of the investigator;

• be serum negative for HBsAg, anti-HBsAg, antibody to hepatitis B core antigen (HBcAg), Hepatitis C virus (HCV), and human immunodeficiency virus (HIV);

• if a woman of childbearing potential, agree to consistently use a highly effective method of birth control from screening visit through the treatment phase and for up to 28 days after the last injection;

• is not scheduled to undergo a kidney transplant in the next 12 months;

• be able and willing to provide informed consent.

Exclusion Criteria:

• if female, is pregnant, breastfeeding, or planning a pregnancy;

• has a history of or is considered by the investigator to be at high risk for recent exposure to HBV, HCV, or HIV; for example, current intravenous drug use, has unprotected sex with known HBV/HIV positive partner;

• has known history of autoimmune disease;

• has previously received any HBV vaccine;

• has a history of sensitivity to any component of study vaccines;

• has current illness other than renal disease or has substance or alcohol abuse that in the opinion of the investigator would interfere with compliance or with interpretation of the study results;

• is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous or basal cell carcinoma of the skin;

• has uncontrolled diabetes or hypertension;

• is unwilling or unable to comply with all the requirements of the protocol;

• has received any blood products or immunoglobulin within 3 months prior to study entry, or likely to require infusion of blood products during the study period;

• has received the following prior to the first injection:

• 3 days: erythropoietin (exclusionary window does not apply for subjects on dialysis)

• 7 days: intravenous iron

• 21 days: any inactivated virus vaccine

• 28 days:

• any live virus vaccine

• systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids

• granulocyte or granulocyte-macrophage colony-simulating factor (G/GM-CSF), any other investigational medicinal agent

• At any time: an injection of deoxyribonucleic acid plasmids or oligonucleotide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Associates of Tidewater	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

• Dynavax Technologies Corporation

Investigators

• Study Director: Robert Janssen, MD, Dynavax Technologies Corporation

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Dynavax Technologies Corporation
• ClinicalTrials.gov Identifier: NCT00985426
• Other Study ID Numbers: DV2-HBV-17; 2009-015877-11
• First Posted: Sep 28, 2009
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Dynavax Technologies Corporation: chronic kidney disease; kidney failure; kidney failure,chronic; chronic kidney failure; hepatitis B virus (HBV) vaccine; hepatitis B vaccine; hepatitis B; hepatitis; HBV; prevention and control; dialysis
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Vaccines

Study Results

Participant Flow

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Subjects randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Period Title: Overall Study
STARTED	258	263
COMPLETED	215	219
NOT COMPLETED	43	44

Baseline Characteristics

Arm/Group Title	HEPLISAV-B	Engerix-B	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	254	262	516
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (9.1)	61.3 (9.7)	61.3 (9.4)
Age, Customized (Count of Participants)
18 to 39 years	3 1.2%	11 4.2%	14 2.7%
40 to 55 years	58 22.8%	52 19.8%	110 21.3%
56 to 75 years	193 76%	199 76%	392 76%
Sex: Female, Male (Count of Participants)
Female	94 37%	104 39.7%	198 38.4%
Male	160 63%	158 60.3%	318 61.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	65 25.6%	71 27.1%	136 26.4%
Not Hispanic or Latino	189 74.4%	191 72.9%	380 73.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.4%	1 0.2%
Asian	3 1.2%	5 1.9%	8 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	1 0.2%
Black or African American	44 17.3%	47 17.9%	91 17.6%
White	204 80.3%	203 77.5%	407 78.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 1.2%	5 1.9%	8 1.6%
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	34.05 (8.45)	32.15 (6.94)	33.09 (7.77)
Smoking status (Count of Participants)
Yes	34 13.4%	43 16.4%	77 14.9%
No	220 86.6%	219 83.6%	439 85.1%
Glomerular Filtration Rate (GFR) at Screening (Count of Participants)
GFR ≤ 15 mL/min/1.73 m2	39 15.4%	55 21%	94 18.2%
GFR 16 - 30 mL/min/1.73 m2	99 39%	96 36.6%	195 37.8%
GFR ≥ 31 mL/min/1.73 m2	116 45.7%	111 42.4%	227 44%
Screening Creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	2.66 (1.42)	2.82 (1.64)	2.74 (1.53)
History of Type 2 Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	173 68.1%	161 61.5%	334 64.7%

Outcome Measures

1. Primary Outcome

Title	Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response
Description	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.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	227	242
Count of Participants [Participants]	204 80.3%	198 75.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HEPLISAV-B, Engerix-B
	Comments	Two-sided 95% confidence intervals (CIs) of the difference in seroprotection rates (SPR) between the HEPLISAV-B group and the Engerix-B group at 28 weeks was computed using the Newcombe score method with continuity correction.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority is achieved if the lower limit of the two-sided 95% CI was greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SPR Difference (%)
	Estimated Value	8
	Confidence Interval	(2-Sided) 95%; 1.7 to 14.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	SPR difference = SPR for HEPLISAV-B minus SPR for Engerix-B.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	HEPLISAV-B, Engerix-B
	Comments	Two-sided 95% CIs of the difference in SPR between the HEPLISAV-B group and the Engerix-B group at 28 weeks was computed using the Newcombe score method with continuity correction.
	Type of Statistical Test	Superiority
	Comments	Superiority is achieved if the lower limit of the two-sided 95% CI was greater than 0%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SPR Difference (%)
	Estimated Value	8
	Confidence Interval	(2-Sided) 95%; 1.7 to 14.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Reactogenicity as Measured by the Percentage of Participants With Local and Systemic Post-injection Reactions Within 7 Days After Each Injection Visit
Description	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.
Time Frame	7 days after each injection visit (Weeks 0, 4, 8, and 24)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	254	262
Local reactions	73 28.7%	90 34.4%
Systemic reactions	85 33.5%	91 34.7%

3. Secondary Outcome

Title	Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52
Description	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.
Time Frame	Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	247	260
Week 4	5.7 2.2%	6.2 2.4%
Week 8	48.1 18.9%	20.2 7.7%
Week 12	65.1 25.6%	50.8 19.4%
Week 18	73.7 29%	59.5 22.7%
Week 24	78.7 31%	62.2 23.7%
Week 28	89.9 35.4%	81.8 31.2%
Week 36	86.9 34.2%	80.3 30.6%
Week 44	83.9 33%	78.6 30%
Week 52	84.3 33.2%	77.3 29.5%

4. Secondary Outcome

Title	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
Time Frame	Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	247	260
Week 4	3.6 1.4%	2.7 1%
Week 8	19.5 7.7%	7 2.7%
Week 12	27.3 10.7%	22.2 8.5%
Week 18	38.6 15.2%	25.9 9.9%
Week 24	45.1 17.8%	28.5 10.9%
Week 28	73.6 29%	63.2 24.1%
Week 36	68.9 27.1%	59 22.5%
Week 44	67.9 26.7%	54.5 20.8%
Week 52	66.8 26.3%	49.1 18.7%

5. Secondary Outcome

Title	Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52
Time Frame	Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	247	260
Week 4	.4	.3
Week 8	8.1	.9
Week 12	16.5	7.2
Week 18	33	12
Week 24	44.3	15.1
Week 28	587.1	156.5
Week 36	302.3	104.2
Week 44	214.5	71.2
Week 52	170.8	51

6. Secondary Outcome

Title	SPR of Participants With Type 2 Diabetes Mellitus at Week 28
Description	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.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HEPLISAV-B	Engerix-B
Arm/Group Description	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.	Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
Measure Participants	153	150
Count of Participants [Participants]	137 53.9%	115 43.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HEPLISAV-B, Engerix-B
	Comments	Two-sided 95% CIs of the difference in SPRs between the HEPLISAV group and the Engerix-B group at 28 weeks was computed using the Newcombe score method with continuity correction.
	Type of Statistical Test	Superiority
	Comments	Superiority is achieved if the lower limit of the two-sided 95% CI was greater than 0%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SPR Difference (%)
	Estimated Value	12.9
	Confidence Interval	(2-Sided) 95%; 4.4 to 21.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	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).
Arm/Group Title	HEPLISAV-B		Engerix-B
Arm/Group Description	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.		Participants randomized to the Engerix-B group received two 1.0-mL IM injections of Engerix-B at Weeks 0, 4, 8, and 24.
All Cause Mortality
	HEPLISAV-B		Engerix-B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/254 (2.8%)		3/262 (1.1%)
Serious Adverse Events
	HEPLISAV-B		Engerix-B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/254 (26.8%)		76/262 (29%)
Blood and lymphatic system disorders
Anaemia	4/254 (1.6%)		1/262 (0.4%)
Coagulopathy	1/254 (0.4%)		0/262 (0%)
Thrombocytopenia	1/254 (0.4%)		0/262 (0%)
Cardiac disorders
Acute coronary syndrome	1/254 (0.4%)		0/262 (0%)
Acute myocardial infarction	3/254 (1.2%)		2/262 (0.8%)
Angina pectoris	0/254 (0%)		3/262 (1.1%)
Angina unstable	2/254 (0.8%)		0/262 (0%)
Atrial fibrillation	0/254 (0%)		1/262 (0.4%)
Cardiac arrest	1/254 (0.4%)		1/262 (0.4%)
Cardiac failure	1/254 (0.4%)		0/262 (0%)
Cardiac failure congestive	8/254 (3.1%)		8/262 (3.1%)
Cardio-respiratory arrest	1/254 (0.4%)		0/262 (0%)
Coronary artery disease	0/254 (0%)		5/262 (1.9%)
Coronary artery insufficiency	1/254 (0.4%)		0/262 (0%)
Myocardial infarction	3/254 (1.2%)		2/262 (0.8%)
Myocardial ischaemia	1/254 (0.4%)		0/262 (0%)
Ear and labyrinth disorders
Vertigo	1/254 (0.4%)		0/262 (0%)
Gastrointestinal disorders
Ascites	1/254 (0.4%)		0/262 (0%)
Diarrhoea	0/254 (0%)		1/262 (0.4%)
Enlarged uvula	0/254 (0%)		1/262 (0.4%)
Gastric ulcer haemorrhage	1/254 (0.4%)		0/262 (0%)
Gastritis erosive	1/254 (0.4%)		0/262 (0%)
Haemorrhoids	0/254 (0%)		1/262 (0.4%)
Inguinal hernia, obstructive	0/254 (0%)		1/262 (0.4%)
Peritonitis	1/254 (0.4%)		0/262 (0%)
Retroperitoneal haematoma	1/254 (0.4%)		0/262 (0%)
General disorders
Generalised oedema	1/254 (0.4%)		1/262 (0.4%)
Hernia obstructive	1/254 (0.4%)		0/262 (0%)
Medical device complication	0/254 (0%)		1/262 (0.4%)
Multi-organ failure	1/254 (0.4%)		0/262 (0%)
Non-cardiac chest pain	2/254 (0.8%)		1/262 (0.4%)
Pyrexia	0/254 (0%)		1/262 (0.4%)
Hepatobiliary disorders
Cholecystitis	0/254 (0%)		2/262 (0.8%)
Infections and infestations
Bacterial pyelonephritis	1/254 (0.4%)		0/262 (0%)
Catheter site infection	0/254 (0%)		1/262 (0.4%)
Cellulitis	1/254 (0.4%)		3/262 (1.1%)
Cellulitis staphylococcal	1/254 (0.4%)		0/262 (0%)
Chronic tonsillitis	0/254 (0%)		1/262 (0.4%)
Clostridium difficile colitis	2/254 (0.8%)		0/262 (0%)
Diabetic foot infection	1/254 (0.4%)		0/262 (0%)
Diverticulitis	1/254 (0.4%)		0/262 (0%)
Enterocolitis infectious	0/254 (0%)		1/262 (0.4%)
Escherichia bacteraemia	1/254 (0.4%)		0/262 (0%)
Escherichia urinary tract infection	1/254 (0.4%)		0/262 (0%)
Fungal peritonitis	0/254 (0%)		1/262 (0.4%)
Gangrene	0/254 (0%)		1/262 (0.4%)
Gastroenteritis	2/254 (0.8%)		1/262 (0.4%)
Gastroenteritis viral	1/254 (0.4%)		1/262 (0.4%)
Influenza	0/254 (0%)		1/262 (0.4%)
Necrotising fasciitis	0/254 (0%)		1/262 (0.4%)
Osteomyelitis	1/254 (0.4%)		2/262 (0.8%)
Perineal abscess	0/254 (0%)		1/262 (0.4%)
Pneumococcal bacteraemia	0/254 (0%)		1/262 (0.4%)
Pneumonia	5/254 (2%)		4/262 (1.5%)
Pneumonia escherichia	1/254 (0.4%)		0/262 (0%)
Renal cyst infection	1/254 (0.4%)		0/262 (0%)
Sepsis	1/254 (0.4%)		0/262 (0%)
Septic shock	1/254 (0.4%)		0/262 (0%)
Staphylococcal sepsis	2/254 (0.8%)		0/262 (0%)
Streptococcal sepsis	1/254 (0.4%)		0/262 (0%)
Urinary tract infection	1/254 (0.4%)		2/262 (0.8%)
Urinary tract infection bacterial	1/254 (0.4%)		0/262 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/254 (0%)		1/262 (0.4%)
Ankle fracture	0/254 (0%)		1/262 (0.4%)
Cervical vertebral fracture	0/254 (0%)		1/262 (0.4%)
Humerus fracture	1/254 (0.4%)		0/262 (0%)
Joint dislocation	1/254 (0.4%)		0/262 (0%)
Lower limb fracture	0/254 (0%)		1/262 (0.4%)
Patella fracture	0/254 (0%)		1/262 (0.4%)
Vascular graft occlusion	1/254 (0.4%)		0/262 (0%)
Investigations
Lipase increased	0/254 (0%)		1/262 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/254 (0.4%)		0/262 (0%)
Diabetic foot	3/254 (1.2%)		0/262 (0%)
Diabetic ketoacidosis	1/254 (0.4%)		0/262 (0%)
Fluid overload	1/254 (0.4%)		2/262 (0.8%)
Hyperglycaemia	1/254 (0.4%)		0/262 (0%)
Hyperglycaemic hyperosmolar nonketotic syndrome	1/254 (0.4%)		0/262 (0%)
Hyperkalaemia	2/254 (0.8%)		0/262 (0%)
Hypoglycaemia	2/254 (0.8%)		2/262 (0.8%)
Hyponatraemia	0/254 (0%)		1/262 (0.4%)
Musculoskeletal and connective tissue disorders
Gouty arthritis	1/254 (0.4%)		0/262 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/254 (0.4%)		0/262 (0%)
Colon adenoma	0/254 (0%)		1/262 (0.4%)
Diffuse large b-cell lymphoma	0/254 (0%)		1/262 (0.4%)
Malignant melanoma	0/254 (0%)		1/262 (0.4%)
Prostate cancer	0/254 (0%)		1/262 (0.4%)
Renal cell carcinoma	0/254 (0%)		1/262 (0.4%)
Thyroid cancer	0/254 (0%)		1/262 (0.4%)
Nervous system disorders
Carotid artery stenosis	1/254 (0.4%)		1/262 (0.4%)
Cerebrovascular accident	1/254 (0.4%)		0/262 (0%)
Hepatic encephalopathy	0/254 (0%)		1/262 (0.4%)
Hypertensive encephalopathy	1/254 (0.4%)		0/262 (0%)
Ischaemic stroke	0/254 (0%)		1/262 (0.4%)
Lacunar infarction	1/254 (0.4%)		0/262 (0%)
Presyncope	1/254 (0.4%)		1/262 (0.4%)
Subarachnoid haemorrhage	0/254 (0%)		1/262 (0.4%)
Syncope	0/254 (0%)		2/262 (0.8%)
Transient ischaemic attack	0/254 (0%)		2/262 (0.8%)
Renal and urinary disorders
Azotaemia	0/254 (0%)		3/262 (1.1%)
Calculus ureteric	0/254 (0%)		1/262 (0.4%)
Renal artery stenosis	0/254 (0%)		1/262 (0.4%)
Renal cyst	1/254 (0.4%)		0/262 (0%)
Renal cyst ruptured	0/254 (0%)		1/262 (0.4%)
Renal failure	1/254 (0.4%)		0/262 (0%)
Renal failure acute	5/254 (2%)		7/262 (2.7%)
Renal failure chronic	9/254 (3.5%)		12/262 (4.6%)
Renal impairment	1/254 (0.4%)		0/262 (0%)
Renal injury	1/254 (0.4%)		0/262 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/254 (0.4%)		1/262 (0.4%)
Bronchiectasis	0/254 (0%)		1/262 (0.4%)
Chronic obstructive pulmonary disease	1/254 (0.4%)		1/262 (0.4%)
Pleural effusion	0/254 (0%)		1/262 (0.4%)
Pulmonary oedema	3/254 (1.2%)		3/262 (1.1%)
Respiratory depression	0/254 (0%)		1/262 (0.4%)
Respiratory failure	1/254 (0.4%)		0/262 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/254 (0.4%)		3/262 (1.1%)
Social circumstances
Victim of homicide	1/254 (0.4%)		0/262 (0%)
Vascular disorders
Deep vein thrombosis	1/254 (0.4%)		0/262 (0%)
Extremity necrosis	1/254 (0.4%)		0/262 (0%)
Haematoma	1/254 (0.4%)		0/262 (0%)
Hypertension	1/254 (0.4%)		4/262 (1.5%)
Hypertensive crisis	2/254 (0.8%)		0/262 (0%)
Hypertensive emergency	1/254 (0.4%)		0/262 (0%)
Hypotension	1/254 (0.4%)		2/262 (0.8%)
Malignant hypertension	0/254 (0%)		1/262 (0.4%)
Peripheral vascular disorder	0/254 (0%)		2/262 (0.8%)
Steal syndrome	0/254 (0%)		1/262 (0.4%)
Other (Not Including Serious) Adverse Events
	HEPLISAV-B		Engerix-B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/254 (55.1%)		146/262 (55.7%)
Blood and lymphatic system disorders
Anaemia	9/254 (3.5%)		11/262 (4.2%)
Eye disorders
Cataract	7/254 (2.8%)		3/262 (1.1%)
Gastrointestinal disorders
Constipation	11/254 (4.3%)		11/262 (4.2%)
Diarrhoea	11/254 (4.3%)		10/262 (3.8%)
Nausea	11/254 (4.3%)		13/262 (5%)
Vomiting	6/254 (2.4%)		8/262 (3.1%)
General disorders
Fatigue	16/254 (6.3%)		13/262 (5%)
Oedema peripheral	16/254 (6.3%)		13/262 (5%)
Infections and infestations
Bronchitis	9/254 (3.5%)		8/262 (3.1%)
Gastroenteritis	7/254 (2.8%)		2/262 (0.8%)
Nasopharyngitis	13/254 (5.1%)		18/262 (6.9%)
Sinusitis	7/254 (2.8%)		7/262 (2.7%)
Upper respiratory tract infection	11/254 (4.3%)		11/262 (4.2%)
Urinary tract infection	12/254 (4.7%)		7/262 (2.7%)
Investigations
Blood creatine phosphokinase increased	7/254 (2.8%)		5/262 (1.9%)
Metabolism and nutrition disorders
Gout	7/254 (2.8%)		7/262 (2.7%)
Hyperkalaemia	11/254 (4.3%)		6/262 (2.3%)
Hyperphosphataemia	4/254 (1.6%)		8/262 (3.1%)
Hypoglycaemia	6/254 (2.4%)		6/262 (2.3%)
Hypokalaemia	9/254 (3.5%)		4/262 (1.5%)
Metabolic acidosis	4/254 (1.6%)		6/262 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/254 (5.9%)		7/262 (2.7%)
Back pain	3/254 (1.2%)		12/262 (4.6%)
Muscle spasms	5/254 (2%)		10/262 (3.8%)
Musculoskeletal pain	5/254 (2%)		7/262 (2.7%)
Myalgia	2/254 (0.8%)		6/262 (2.3%)
Pain in extremity	8/254 (3.1%)		11/262 (4.2%)
Nervous system disorders
Dizziness	4/254 (1.6%)		8/262 (3.1%)
Headache	9/254 (3.5%)		8/262 (3.1%)
Psychiatric disorders
Insomnia	6/254 (2.4%)		1/262 (0.4%)
Renal and urinary disorders
Renal failure chronic	11/254 (4.3%)		13/262 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	11/254 (4.3%)		9/262 (3.4%)
Dyspnoea	8/254 (3.1%)		9/262 (3.4%)
Oropharyngeal pain	4/254 (1.6%)		6/262 (2.3%)
Skin and subcutaneous tissue disorders
Pruritus	2/254 (0.8%)		8/262 (3.1%)
Vascular disorders
Hypertension	8/254 (3.1%)		18/262 (6.9%)
Hypotension	6/254 (2.4%)		7/262 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.