Safety and Immunogenicity Study of the Hepatitis B Virus (HBV) Vaccine, HEPLISAV Compared to Engerix-B Vaccine

• Sponsor: Dynavax Technologies Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01005407
• Collaborator: (none)
• Enrollment: 2,452
• Locations: 32
• Arms: 2
• Duration (Months): 14.9
• Patients Per Site: 76.6
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety, immunogenicity and lot-to-lot consistency of an investigational hepatitis B virus vaccine, HEPLISAV™, in healthy adults 40 to 70 years of age

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: HEPLISAV and/or Placebo; Biological: Engerix-B	Phase 3

Detailed Description

The purpose of the study is to evaluate the safety, immunogenicity and lot-to-lot consistency of an investigational hepatitis B virus vaccine, HEPLISAV™, in healthy adults 40 to 70 years of age

Study Design

• Study Type: Interventional
• Actual Enrollment: 2452 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: An Observer-Blinded, Randomized, Parallel-Group, Multi-Center Study Comparing the Safety and Immunogenicity of HEPLISAV™ to Licensed Vaccine (Engerix-B®) Among Healthy Subjects 40 to 70 Years of Age
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HEPLISAV and/or Placebo 0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018)	Biological: HEPLISAV and/or Placebo; Intramuscular (IM) injections on Week 0 and Week 4; placebo (saline) injection at Week 24; Other Names: Hepatitis B vaccine (recombinant), adjuvanted
Active Comparator: Engerix-B(1) 1.0 mL Engerix-B	Biological: Engerix-B; Intramuscular (IM) injections on Week 0, Week 4 and Week 24; Other Names: Hepatitis B vaccine (recombinant)

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Who Have a Seroprotective Immune Response [at Week 12 and at Week 32]

   Percentage of subjects who have a seroprotective immune response (anti-HBsAg antibody≥ 10 milli-international unit (mIU)/mL) 8 weeks after the last active dose of HEPLISAV™ compared to 8 weeks after the last active dose of Engerix-B®

Secondary Outcome Measures

1. Percentage of Participants With Local and Systemic Reaction to Injections [within 7 days for post-injection reactions]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• be 40 - 70 years of age, inclusive

• be seronegative for hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBsAg), antibody against hepatitis B core antigen (anti-HBcAg), and human immunodeficiency virus (HIV)

• be in good health in the opinion of the investigator, based upon medical history, physical examination, and laboratory evaluation

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

Exclusion Criteria:

• if female of childbearing potential, 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 or HIV; for example, current intravenous drug use or has unprotected sex with known HBV/HIV positive partner

• has a known history of autoimmune disease

• has previously received any hepatitis B vaccine (approved or investigational)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		San Diego	California	United States
3		Santa Ana	California	United States
4		Denver	Colorado	United States
5		Melbourne	Florida	United States
6		Pinellas Park	Florida	United States
7		Atlanta	Georgia	United States
8		Chicago	Illinois	United States
9		Peoria	Illinois	United States
10		South Bend	Indiana	United States
11		Rockville	Maryland	United States
12		Brooklyn Center	Minnesota	United States
13		Edina	Minnesota	United States
14		Kansas City	Missouri	United States
15		Saint Louis	Missouri	United States
16		Rochester	New York	United States
17		Cincinnati	Ohio	United States
18		Erie	Pennsylvania	United States
19		Grove City	Pennsylvania	United States
20		Jefferson Hills	Pennsylvania	United States
21		Pittsburgh	Pennsylvania	United States
22		Upper Saint Clair	Pennsylvania	United States
23		Anderson	South Carolina	United States
24		Greer	South Carolina	United States
25		Nashville	Tennessee	United States
26		Dallas	Texas	United States
27		Katy	Texas	United States
28		San Antonio	Texas	United States
29		Norfolk	Virginia	United States
30		Mount Pearl	Newfoundland and Labrador	Canada
31		Toronto	Ontario	Canada
32		Montreal	Quebec	Canada

Sponsors and Collaborators

• Dynavax Technologies Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dynavax Technologies Corporation
• ClinicalTrials.gov Identifier: NCT01005407
• Other Study ID Numbers: DV2-HBV-16
• First Posted: Nov 1, 2009
• Last Update Posted: Mar 20, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dynavax Technologies Corporation: HBV vaccine; Hepatitis B vaccine; Hepatitis B; Hepatitis; HBV; Prevention & Control; Healthy; Healthy volunteers
• Additional relevant MeSH terms: Hepatitis B; Vaccines

Study Results

Participant Flow

Arm/Group Title	HEPLISAV and/or Placebo	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	1969	483
COMPLETED	1818	451
NOT COMPLETED	151	32

Baseline Characteristics

Arm/Group Title	HEPLISAV and Placebo	Engerix-B	Total
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 (IM) injections on Week 0, Week 4 and Week 24	Total of all reporting groups
Overall Participants	1968	481	2449
Age, Customized (Count of Participants)
≥ 40 to ≤ 70 years	1968 100%	481 100%	2449 100%
Sex: Female, Male (Count of Participants)
Female	1025 52.1%	245 50.9%	1270 51.9%
Male	943 47.9%	236 49.1%	1179 48.1%
Region of Enrollment (Count of Participants)
Canada	151 7.7%	45 9.4%	196 8%
United States	1817 92.3%	436 90.6%	2253 92%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who Have a Seroprotective Immune Response
Description	Percentage of subjects who have a seroprotective immune response (anti-HBsAg antibody≥ 10 milli-international unit (mIU)/mL) 8 weeks after the last active dose of HEPLISAV™ compared to 8 weeks after the last active dose of Engerix-B®
Time Frame	at Week 12 and at Week 32

Outcome Measure Data

Analysis Population Description

Non-Inferiority per Protocol population:Randomized subjects who received 1 of 3 consistency lots of HEPLISAV or Engerix-B within the study visit windows, had all 3 study injections as randomized and within the study visit windows, no major protocol deviations, and anti-HBs levels obtained within study visit windows at baseline, Week 12, and Week 32

Arm/Group Title	HEPLISAV and Placebo	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 (IM) injections on Week 0, Week 4 and Week 24
Measure Participants	1121	353
Number [Percentage of participants]	90.1 4.6%	70.5 14.7%

2. Secondary Outcome

Title	Percentage of Participants With Local and Systemic Reaction to Injections
Time Frame	within 7 days for post-injection reactions

Outcome Measure Data

Analysis Population Description

Safety population: All participants who received at least 1 study injection and had at least 1 post-baseline safety data. NOTE: Only subjects with non-missing injection results in the Safety population are included in this analysis.

Arm/Group Title	HEPLISAV and Placebo	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 (IM) injections on Week 0, Week 4 and Week 24
Measure Participants	1952	477
Local reaction: Injection 1	24.33 1.2%	18.87 3.9%
Local reaction: Injection 2	23.10 1.2%	16.16 3.4%
Local reaction: Injection 3	0 0%	13.84 2.9%
Systemic reaction: Injection 1	22.34 1.1%	22.64 4.7%
Systemic reaction: Injection 2	16.38 0.8%	18.10 3.8%
Systemic reaction: Injection 3	0 0%	13.39 2.8%

Adverse Events

Adverse Event Reporting Description	Adverse events were assessed for the safety analysis population: All participants who received at least 1 study injection and had a least 1 post baseline safety data
Arm/Group Title	HEPLISAV and/or Placebo		Engerix-B(1)
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 (IM) injections on Week 0, Week 4 and Week 24
All Cause Mortality
	HEPLISAV and/or Placebo		Engerix-B(1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	HEPLISAV and/or Placebo		Engerix-B(1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/1968 (4%)		23/481 (4.8%)
Blood and lymphatic system disorders
Anaemia	0/1968 (0%)		1/481 (0.2%)
Cardiac disorders
Acute myocardial infarction	2/1968 (0.1%)		1/481 (0.2%)
Angina pectoris	1/1968 (0.1%)		0/481 (0%)
Angina unstable	0/1968 (0%)		1/481 (0.2%)
Atrial fibrillation	1/1968 (0.1%)		0/481 (0%)
Cardiac failure	0/1968 (0%)		1/481 (0.2%)
Cardiomyopathy	1/1968 (0.1%)		0/481 (0%)
Coronary artery disease	2/1968 (0.1%)		1/481 (0.2%)
Coronary artery stenosis	0/1968 (0%)		1/481 (0.2%)
Ear and labyrinth disorders
Vertigo	1/1968 (0.1%)		0/481 (0%)
Gastrointestinal disorders
Abdominal hernia	1/1968 (0.1%)		0/481 (0%)
Barrett's oesophagus	0/1968 (0%)		1/481 (0.2%)
Erosive oesophagitis	1/1968 (0.1%)		0/481 (0%)
Gastric haemorrhage	0/1968 (0%)		1/481 (0.2%)
Gastric ulcer	1/1968 (0.1%)		0/481 (0%)
Gastrooesophageal reflux disease	1/1968 (0.1%)		0/481 (0%)
Haematemesis	1/1968 (0.1%)		0/481 (0%)
Inguinal hernia	1/1968 (0.1%)		0/481 (0%)
Small intestinal obstruction	1/1968 (0.1%)		0/481 (0%)
General disorders
Chest pain	0/1968 (0%)		1/481 (0.2%)
Non-cardiac chest pain	3/1968 (0.2%)		1/481 (0.2%)
Hepatobiliary disorders
Cholecystitis	1/1968 (0.1%)		0/481 (0%)
Infections and infestations
Cavernous sinus thrombosis	1/1968 (0.1%)		0/481 (0%)
Diverticulitis	1/1968 (0.1%)		0/481 (0%)
Gastroenteritis salmonella	0/1968 (0%)		1/481 (0.2%)
Localised infection	1/1968 (0.1%)		0/481 (0%)
Perirectal abscess	1/1968 (0.1%)		0/481 (0%)
Pneumonia	1/1968 (0.1%)		0/481 (0%)
Post procedural infection	1/1968 (0.1%)		0/481 (0%)
Staphylococcal infection	1/1968 (0.1%)		0/481 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	2/1968 (0.1%)		0/481 (0%)
Ankle fracture	2/1968 (0.1%)		0/481 (0%)
Contusion	1/1968 (0.1%)		0/481 (0%)
Delayed recovery from anaesthesia	0/1968 (0%)		1/481 (0.2%)
Fall	1/1968 (0.1%)		0/481 (0%)
Fibula fracture	1/1968 (0.1%)		0/481 (0%)
Foot fracture	1/1968 (0.1%)		0/481 (0%)
Gun shot wound	1/1968 (0.1%)		0/481 (0%)
Joint injury	1/1968 (0.1%)		1/481 (0.2%)
Meniscus injury	1/1968 (0.1%)		1/481 (0.2%)
Muscle strain	1/1968 (0.1%)		0/481 (0%)
Thermal burn	1/1968 (0.1%)		0/481 (0%)
Tibia fracture	1/1968 (0.1%)		0/481 (0%)
Metabolism and nutrition disorders
Dehydration	0/1968 (0%)		1/481 (0.2%)
Diabetic ketoacidosis	1/1968 (0.1%)		0/481 (0%)
Hyperglycaemia	1/1968 (0.1%)		0/481 (0%)
Hypokalaemia	1/1968 (0.1%)		0/481 (0%)
Hyponatraemia	2/1968 (0.1%)		0/481 (0%)
Water intoxication	1/1968 (0.1%)		0/481 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	0/1968 (0%)		1/481 (0.2%)
Intervertebral disc degeneration	1/1968 (0.1%)		1/481 (0.2%)
Intervertebral disc protrusion	4/1968 (0.2%)		0/481 (0%)
Loose body in joint	1/1968 (0.1%)		0/481 (0%)
Lumbar spinal stenosis	1/1968 (0.1%)		1/481 (0.2%)
Musculoskeletal chest pain	1/1968 (0.1%)		0/481 (0%)
Neck pain	1/1968 (0.1%)		0/481 (0%)
Osteoarthritis	9/1968 (0.5%)		2/481 (0.4%)
Spinal column stenosis	2/1968 (0.1%)		0/481 (0%)
Spondylolisthesis	1/1968 (0.1%)		0/481 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	1/1968 (0.1%)		0/481 (0%)
Breast cancer	1/1968 (0.1%)		1/481 (0.2%)
Colon adenoma	2/1968 (0.1%)		0/481 (0%)
Colon cancer stage iv	1/1968 (0.1%)		0/481 (0%)
Inflammatory carcinoma of the breast	1/1968 (0.1%)		0/481 (0%)
Invasive ductal breast carcinoma	0/1968 (0%)		1/481 (0.2%)
Non-small cell lung cancer metastatic	1/1968 (0.1%)		0/481 (0%)
Prostate cancer	1/1968 (0.1%)		3/481 (0.6%)
Uterine leiomyoma	1/1968 (0.1%)		0/481 (0%)
Nervous system disorders
Benign intracranial hypertension	0/1968 (0%)		1/481 (0.2%)
Spondylitic myelopathy	1/1968 (0.1%)		0/481 (0%)
Subarachnoid haemorrhage	1/1968 (0.1%)		0/481 (0%)
Psychiatric disorders
Major depression	1/1968 (0.1%)		0/481 (0%)
Reproductive system and breast disorders
Endometriosis	1/1968 (0.1%)		0/481 (0%)
Haemorrhagic ovarian cyst	0/1968 (0%)		1/481 (0.2%)
Menstruation irregular	1/1968 (0.1%)		0/481 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/1968 (0.1%)		0/481 (0%)
Bronchial hyperreactivity	0/1968 (0%)		1/481 (0.2%)
Chronic obstructive pulmonary disease	1/1968 (0.1%)		1/481 (0.2%)
Hypoxia	1/1968 (0.1%)		0/481 (0%)
Pulmonary embolism	2/1968 (0.1%)		0/481 (0%)
Vascular disorders
Deep vein thrombosis	2/1968 (0.1%)		1/481 (0.2%)
Hypertension	1/1968 (0.1%)		0/481 (0%)
Other (Not Including Serious) Adverse Events
	HEPLISAV and/or Placebo		Engerix-B(1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/1968 (4.1%)		25/481 (5.2%)
Infections and infestations
Nasopharyngitis	80/1968 (4.1%)		25/481 (5.2%)

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.