Safety and Immunogenicity Study of the Hepatitis B Vaccine, HEPLISAV™, Compared to Engerix-B® Vaccine

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ClinicalTrials.gov Identifier: NCT02117934

Recruitment Status : Completed

First Posted : April 21, 2014

Results First Posted : January 10, 2018

Last Update Posted : March 20, 2019

Sponsor:

Information provided by (Responsible Party):

Dynavax Technologies Corporation

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition	Healthy
Interventions	Biological: HEPLISAV Biological: Engerix-B
Enrollment	8374

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	HEPLISAV	Engerix-B
Arm/Group Description	0.5 mL HEPLISAV (20 mcg HBsAg and 3...	1.0 mL Engerix-B ...
Arm/Group Description	0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) HEPLISAV and/or Placebo: Intramuscular (IM) injections at Week 0, Week 4, plus a placebo (saline) injection at Week 24	1.0 mL Engerix-B Engerix-B: Intramuscular injections at Week 0, Week 4, and Week 24
Period Title: Overall Study
Started	5592	2782
Completed	5092	2567
Not Completed	500	215

Baseline Characteristics

Arm/Group Title		HEPLISAV	Engerix-B	Total
Arm/Group Description		0.5 mL HEPLISAV (20 mcg HBsAg and 3...	1.0 mL Engerix-B ...	Total of all reporting groups
Arm/Group Description		0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) HEPLISAV and/or Placebo: Intramuscular (IM) injections at Week 0, Week 4, plus a placebo (saline) injection at Week 24	1.0 mL Engerix-B Engerix-B: Intramuscular injections at Week 0, Week 4, and Week 24	Total of all reporting groups
Overall Number of Baseline Participants		5587	2781	8368
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Safety Population: All subjects who received at least 1 study injection and who had any post-baseline safety data
Age, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	5587 participants	2781 participants	8368 participants
Age ≥ 18 to ≤ 39 years		1132 20.3%	561 20.2%	1693 20.2%
Age ≥ 40 years		4455 79.7%	2220 79.8%	6675 79.8%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	5587 participants	2781 participants	8368 participants
	Female	2743 49.1%	1390 50.0%	4133 49.4%
	Male	2844 50.9%	1391 50.0%	4235 50.6%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	5587 participants	2781 participants	8368 participants
United States		5587 100.0%	2781 100.0%	8368 100.0%

Outcome Measures

1.Primary Outcome


Title	Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest
Description	The percentage of participants with Medically-attended adverse events ...
Description	The percentage of participants with Medically-attended adverse events (MAEs), Serious Adverse Events (SAEs), and immune-mediated Adverse Events of Special Interest (AESIs). MAEs are Adverse events (AEs) for which a subject sought medical attention at a doctor's office, clinic or study site, or emergency room, or was hospitalized. SAEs are AEs that met the definition of Serious per FDA regulations. Immune-mediated AESIs are AEs that were confirmed to be autoimmune in etiology.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Safety Population: All participants who received at least 1 study injection and who had any post-baseline safety data


Arm/Group Title	HEPLISAV	Engerix-B
Arm/Group Description:	0.5 mL HEPLISAV (20 mcg HBsAg and 3...	1.0 mL Engerix-B ...
Arm/Group Description:	0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) HEPLISAV and/or Placebo: Intramuscular (IM) injections at Week 0, Week 4, plus a placebo (saline) injection at Week 24	1.0 mL Engerix-B Engerix-B: Intramuscular injections at Week 0, Week 4, and Week 24
Overall Number of Participants Analyzed	5587	2781
Measure Type: Number Unit of Measure: percentage of participants
New-onset Immune-mediated Adverse Events	0.1	0.04
Medically-attended Adverse Events	46.0	46.2
Serious Adverse Events	6.2	5.3

2.Primary Outcome


Title	Percentage of Subjects With Type 2 Diabetes Mellitus Who Have a Seroprotective Immune Response
Description	Percentage of subjects with type 2 diabetes mellitus who have a seropr...
Description	Percentage of subjects with type 2 diabetes mellitus who have a seroprotective immune response (anti-HBs ≥ 10 milli-international unit (mIU)/mL) who receive HEPLISAV compared with subjects who receive Engerix-B
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-Protocol Diabetes Population:Randomized subjects with type 2 diabetes mellitus (clinical diagnosis of T2DM taking at least oral or non-insulin injectable hypoglycemic agent and/or insulin) who received all study injections, had no major protocol deviations, and had anti-HBs levels obtained within the study visit window at Week 28.


Arm/Group Title	HEPLISAV	Engerix-B
Arm/Group Description:	0.5 mL HEPLISAV (20 mcg HBsAg and 3...	1.0 mL Engerix-B ...
Arm/Group Description:	0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) HEPLISAV and/or Placebo: Intramuscular (IM) injections at Week 0, Week 4, plus a placebo (saline) injection at Week 24	1.0 mL Engerix-B Engerix-B: Intramuscular injections at Week 0, Week 4, and Week 24
Overall Number of Participants Analyzed	640	321
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	90.0 (87.4 to 92.2)	65.1 (59.6 to 70.3)

Adverse Events

Time Frame	Through Week 56
Adverse Event Reporting Description	Adverse Events were assessed for the Safety Population: All participants who received at least 1 study injection and who had any post-baseline safety data.

Arm/Group Title	HEPLISAV	Engerix-B
Arm/Group Description	0.5 mL HEPLISAV (20 mcg HBsAg and 3...	1.0 mL Engerix-B ...
Arm/Group Description	0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) HEPLISAV and/or Placebo: Intramuscular (IM) injections at Week 0, Week 4, plus a placebo (saline) injection at Week 24	1.0 mL Engerix-B Engerix-B: Intramuscular injections at Week 0, Week 4, and Week 24
All-Cause Mortality
	HEPLISAV	Engerix-B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	HEPLISAV	Engerix-B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	345/5587 (6.18%)	148/2781 (5.32%)
Blood and lymphatic system disorders
Anaemia ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Anaemia vitamin b12 deficiency ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Leukocytosis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Microcytic anaemia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cardiac disorders
Acute coronary syndrome ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Acute myocardial infarction ^† 1	14/5587 (0.25%)	1/2781 (0.04%)
Angina pectoris ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Angina unstable ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Atrial fibrillation ^† 1	6/5587 (0.11%)	3/2781 (0.11%)
Atrial flutter ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Bradycardia ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Cardiac arrest ^† 1	3/5587 (0.05%)	0/2781 (0.00%)
Cardiac failure ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Cardiac failure acute ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cardiac failure congestive ^† 1	6/5587 (0.11%)	3/2781 (0.11%)
Cardiac ventricular thrombosis ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Cardio-respiratory arrest ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Cardiogenic shock ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cardiomyopathy ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Coronary artery disease ^† 1	6/5587 (0.11%)	2/2781 (0.07%)
Coronary artery occlusion ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Coronary artery stenosis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Hypertensive heart disease ^† 1	4/5587 (0.07%)	1/2781 (0.04%)
Myocardial infarction ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Myocardial ischaemia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pulseless electrical activity ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Supraventricular tachycardia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ventricular fibrillation ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ventricular tachycardia ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Congenital, familial and genetic disorders
Atrial septal defect ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ebstein's anomaly ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Sickle cell anaemia with crisis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ear and labyrinth disorders
Vertigo ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Vertigo positional ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pituitary-dependent cushing's syndrome ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Thyroid mass ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gastrointestinal disorders
Abdominal hernia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Abdominal pain ^† 1	2/5587 (0.04%)	2/2781 (0.07%)
Appendix disorder ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Colitis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Colitis ulcerative ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Constipation ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Cyclic vomiting syndrome ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Diarrhoea ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Diverticular perforation ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Diverticulum intestinal haemorrhagic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Duodenal ulcer haemorrhage ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gastric ulcer ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gastric ulcer haemorrhage ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Gastritis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Gastritis alcoholic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Gastritis alcoholic haemorrhagic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Gastritis haemorrhagic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Gastrointestinal haemorrhage ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Gastrooesophageal reflux disease ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Ileus ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ileus paralytic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Impaired gastric emptying ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Inguinal hernia ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Intestinal obstruction ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Large intestine perforation ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Lower gastrointestinal haemorrhage ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Oesophageal spasm ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Oesophagitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pancreatitis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Pancreatitis acute ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Rectal haemorrhage ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Rectal prolapse ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Small intestinal obstruction ^† 1	6/5587 (0.11%)	2/2781 (0.07%)
Upper gastrointestinal haemorrhage ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Varices oesophageal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
General disorders
Chest pain ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Death ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Device failure ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Drug withdrawal syndrome ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Non-cardiac chest pain ^† 1	9/5587 (0.16%)	7/2781 (0.25%)
Hepatobiliary disorders
Bile duct stone ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Cholecystitis ^† 1	5/5587 (0.09%)	2/2781 (0.07%)
Cholecystitis acute ^† 1	0/5587 (0.00%)	2/2781 (0.07%)
Cholecystitis chronic ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Cholelithiasis ^† 1	4/5587 (0.07%)	4/2781 (0.14%)
Hepatic cirrhosis ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Ischaemic hepatitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Immune system disorders
Hypersensitivity ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Infections and infestations
Abscess limb ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Abscess neck ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Appendicitis ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Appendicitis perforated ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Arthritis bacterial ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Bacteraemia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Bronchitis ^† 1	3/5587 (0.05%)	0/2781 (0.00%)
Cellulitis ^† 1	7/5587 (0.13%)	4/2781 (0.14%)
Cellulitis of male external genital organ ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cellulitis orbital ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Cholecystitis infective ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Clostridium difficile colitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Device related infection ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Diabetic foot infection ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Diverticulitis ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Erysipelas ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gastroenteritis ^† 1	4/5587 (0.07%)	1/2781 (0.04%)
Gastroenteritis viral ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Groin abscess ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Hepatitis c ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Infectious colitis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Influenza ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Latent tuberculosis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Lobar pneumonia ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Meningitis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Mycobacterium avium complex infection ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Osteomyelitis ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Otitis media bacterial ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Periorbital cellulitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Perirectal abscess ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Pneumonia ^† 1	15/5587 (0.27%)	8/2781 (0.29%)
Pneumonia escherichia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pneumonia staphylococcal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Post procedural infection ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Postoperative wound infection ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Pyelonephritis ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Pyelonephritis acute ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Sepsis ^† 1	5/5587 (0.09%)	1/2781 (0.04%)
Splenic abscess ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Staphylococcal abscess ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Staphylococcal osteomyelitis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Upper respiratory tract infection ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Urinary tract infection ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Urinary tract infection enterococcal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Urosepsis ^† 1	4/5587 (0.07%)	2/2781 (0.07%)
Viral sepsis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Wound infection ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Wound infection staphylococcal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Injury, poisoning and procedural complications
Accident ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Accidental overdose ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Ankle fracture ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Arterial injury ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cervical vertebral fracture ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Concussion ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Craniocerebral injury ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Facial bones fracture ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Femoral neck fracture ^† 1	0/5587 (0.00%)	2/2781 (0.07%)
Femur fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Foot fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Forearm fracture ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gastrointestinal anastomotic leak ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Gun shot wound ^† 1	3/5587 (0.05%)	0/2781 (0.00%)
Hand fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Head injury ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Hip fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Humerus fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Intentional overdose ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Jaw fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Laceration ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Lower limb fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Lumbar vertebral fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Overdose ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Patella fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Peripheral nerve injury ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Post procedural haematoma ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Postoperative fever ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Postoperative ileus ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Procedural intestinal perforation ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Procedural pain ^† 1	0/5587 (0.00%)	2/2781 (0.07%)
Rib fracture ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Scapula fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Seroma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Spinal fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Stab wound ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Tibia fracture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Toxicity to various agents ^† 1	5/5587 (0.09%)	1/2781 (0.04%)
Traumatic haemothorax ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Urinary retention postoperative ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Wrist fracture ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Investigations
Electrophoresis protein abnormal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Foetal heart rate abnormal ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
International normalised ratio increased ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Metabolism and nutrition disorders
Dehydration ^† 1	1/5587 (0.02%)	3/2781 (0.11%)
Diabetes mellitus inadequate control ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Diabetic ketoacidosis ^† 1	5/5587 (0.09%)	1/2781 (0.04%)
Dyslipidaemia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hypoglycaemia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hypokalaemia ^† 1	2/5587 (0.04%)	2/2781 (0.07%)
Hyponatraemia ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Type 2 diabetes mellitus ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Bursitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Costochondritis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Flank pain ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Intervertebral disc degeneration ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Intervertebral disc protrusion ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Lumbar spinal stenosis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Muscular weakness ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Musculoskeletal chest pain ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Myositis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Neck pain ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Osteoarthritis ^† 1	7/5587 (0.13%)	3/2781 (0.11%)
Rhabdomyolysis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Rotator cuff syndrome ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Spinal column stenosis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Spinal osteoarthritis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Spondylolisthesis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Vertebral foraminal stenosis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Brain neoplasm benign ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Breast cancer ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Cervix carcinoma ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Cholangiocarcinoma ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Clear cell renal cell carcinoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Colon adenoma ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Ductal adenocarcinoma of pancreas ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Endometrial cancer ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hodgkin's disease ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Intraductal papillary mucinous neoplasm ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Intraductal proliferative breast lesion ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Invasive ductal breast carcinoma ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Lung adenocarcinoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Lung cancer metastatic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Malignant melanoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Metastatic renal cell carcinoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Oesophageal adenocarcinoma ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Ovarian cancer stage iii ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Ovarian germ cell teratoma ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Pancreatic carcinoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pancreatic carcinoma metastatic ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Papillary thyroid cancer ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Pelvic neoplasm ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Plasma cell myeloma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Prostate cancer ^† 1	3/5587 (0.05%)	4/2781 (0.14%)
Prostate cancer stage ii ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Rectal adenocarcinoma ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Small cell lung cancer metastatic ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Squamous cell carcinoma of the cervix ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Squamous cell carcinoma of the oral cavity ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Uterine leiomyoma ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Nervous system disorders
Carotid artery stenosis ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Carotid sinus syndrome ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Cauda equina syndrome ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Cerebrovascular accident ^† 1	7/5587 (0.13%)	3/2781 (0.11%)
Cervical myelopathy ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Complex partial seizures ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Convulsion ^† 1	4/5587 (0.07%)	1/2781 (0.04%)
Dizziness ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Embolic stroke ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Haemorrhagic stroke ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Headache ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hepatic encephalopathy ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hypoaesthesia ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Hypoxic-ischaemic encephalopathy ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Ischaemic stroke ^† 1	2/5587 (0.04%)	1/2781 (0.04%)
Lacunar infarction ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Lumbar radiculopathy ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Migraine ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Neuropathy peripheral ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Radial nerve palsy ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Spondylitic myelopathy ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Subarachnoid haemorrhage ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Syncope ^† 1	2/5587 (0.04%)	4/2781 (0.14%)
Thalamic infarction ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Thrombotic stroke ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Transient global amnesia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Transient ischaemic attack ^† 1	4/5587 (0.07%)	1/2781 (0.04%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous ^† 1	3/5587 (0.05%)	2/2781 (0.07%)
Foetal growth restriction ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Gestational diabetes ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Oligohydramnios ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Placenta praevia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Psychiatric disorders
Bipolar disorder ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Bipolar i disorder ^† 1	4/5587 (0.07%)	0/2781 (0.00%)
Confusional state ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Delirium ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Depression ^† 1	5/5587 (0.09%)	1/2781 (0.04%)
Depression suicidal ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Mental status changes ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Schizoaffective disorder ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Schizophrenia ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Substance-induced psychotic disorder ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Suicidal ideation ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Suicide attempt ^† 1	3/5587 (0.05%)	1/2781 (0.04%)
Renal and urinary disorders
Acute prerenal failure ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Bladder disorder ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Calculus ureteric ^† 1	4/5587 (0.07%)	2/2781 (0.07%)
Nephrolithiasis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Prerenal failure ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Renal failure ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Renal failure acute ^† 1	4/5587 (0.07%)	3/2781 (0.11%)
Renal failure chronic ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Tubulointerstitial nephritis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Urinary retention ^† 1	0/5587 (0.00%)	2/2781 (0.07%)
Reproductive system and breast disorders
Adenomyosis ^† 1	0/5587 (0.00%)	2/2781 (0.07%)
Cystocele ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Dysfunctional uterine bleeding ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Postmenopausal haemorrhage ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Prostatitis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Vaginal haemorrhage ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Acute respiratory failure ^† 1	6/5587 (0.11%)	1/2781 (0.04%)
Asthma ^† 1	5/5587 (0.09%)	1/2781 (0.04%)
Chronic obstructive pulmonary disease ^† 1	9/5587 (0.16%)	3/2781 (0.11%)
Diaphragmatic paralysis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Diaphragmatic rupture ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Dyspnoea ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Haemothorax ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hiccups ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Hypoxia ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Lung infiltration ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Nasal polyps ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pleural effusion ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Pleuritic pain ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Pneumonia aspiration ^† 1	1/5587 (0.02%)	1/2781 (0.04%)
Pneumothorax ^† 1	4/5587 (0.07%)	1/2781 (0.04%)
Pulmonary embolism ^† 1	3/5587 (0.05%)	2/2781 (0.07%)
Pulmonary oedema ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Respiratory arrest ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Respiratory failure ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Skin and subcutaneous tissue disorders
Diabetic foot ^† 1	1/5587 (0.02%)	2/2781 (0.07%)
Hidradenitis ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Social circumstances
Victim of homicide ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Vascular disorders
Aortic aneurysm ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Aortic stenosis ^† 1	0/5587 (0.00%)	1/2781 (0.04%)
Deep vein thrombosis ^† 1	4/5587 (0.07%)	3/2781 (0.11%)
Hypertension ^† 1	5/5587 (0.09%)	3/2781 (0.11%)
Hypertensive crisis ^† 1	2/5587 (0.04%)	0/2781 (0.00%)
Hypotension ^† 1	2/5587 (0.04%)	2/2781 (0.07%)
Peripheral vascular disorder ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
Thrombophlebitis superficial ^† 1	1/5587 (0.02%)	0/2781 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	HEPLISAV	Engerix-B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1097/5587 (19.63%)	549/2781 (19.74%)
Infections and infestations
Acute sinusitis ^† 1	59/5587 (1.06%)	37/2781 (1.33%)
Bronchitis ^† 1	174/5587 (3.11%)	102/2781 (3.67%)
Sinusitis ^† 1	149/5587 (2.67%)	84/2781 (3.02%)
Upper respiratory tract infection ^† 1	191/5587 (3.42%)	92/2781 (3.31%)
Urinary tract infection ^† 1	132/5587 (2.36%)	63/2781 (2.27%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus ^† 1	66/5587 (1.18%)	36/2781 (1.29%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	98/5587 (1.75%)	54/2781 (1.94%)
Back pain ^† 1	115/5587 (2.06%)	54/2781 (1.94%)
Musculoskeletal pain ^† 1	45/5587 (0.81%)	30/2781 (1.08%)
Osteoarthritis ^† 1	72/5587 (1.29%)	30/2781 (1.08%)
Pain in extremity ^† 1	72/5587 (1.29%)	28/2781 (1.01%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	62/5587 (1.11%)	37/2781 (1.33%)
Vascular disorders
Hypertension ^† 1	128/5587 (2.29%)	57/2781 (2.05%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 17.0

Limitations and Caveats

[Not Specified]

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Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Principal Investigator may communicate study results with prior written consent from Dynavax.

Results Point of Contact

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Name/Title:	Robert Janssen MD \ VP & Chief Medical Officer
Organization:	Dynavax Technologies, Inc.
Phone:	510-848-5100

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hyer RN, Janssen RS. Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpG 1018, in persons with diabetes mellitus aged 60-70 years. Vaccine. 2019 Sep 16;37(39):5854-5861. doi: 10.1016/j.vaccine.2019.08.005. Epub 2019 Aug 17.

Jackson S, Lentino J, Kopp J, Murray L, Ellison W, Rhee M, Shockey G, Akella L, Erby K, Heyward WL, Janssen RS; HBV-23 Study Group. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018 Jan 29;36(5):668-674. doi: 10.1016/j.vaccine.2017.12.038. Epub 2017 Dec 27.

Layout table for additonal information

Responsible Party:	Dynavax Technologies Corporation
ClinicalTrials.gov Identifier:	NCT02117934
Other Study ID Numbers:	DV2-HBV-23
First Submitted:	April 15, 2014
First Posted:	April 21, 2014
Results First Submitted:	December 8, 2017
Results First Posted:	January 10, 2018
Last Update Posted:	March 20, 2019

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