Hepatitis B
Conditions
Keywords
HBV vaccine, Hepatitis B vaccine, Hepatitis B, Hepatitis, HBV, Immunostimulatory sequence (ISS)
Brief summary
The purpose of this study is to find out if a new investigational hepatitis B virus vaccine, HEPLISAV™, is safe and effective compared with Engerix-B® vaccine in subjects 11-55 years old. The primary hypothesis is that the seroprotective immune response of HEPLISAV™ is at least as good as that of Engerix-B®.
Detailed description
This study will evaluate the safety and efficacy of two injections of HEPLISAV™, compared with three injections of a commercially available hepatitis B virus (HBV) vaccine, Engerix-B®, in subjects 11 to 55 years old. About 2,400 subjects will be included in the study. Once subjects are consented, screened, and randomized to treatment, all subjects will receive a total of three injections over a 24-week period, with a follow-up visit at 28 weeks. Subjects randomized to Engerix-B® will receive 3 injections of active vaccine, while subjects randomized to HEPLISAV™ will receive 2 injections of active vaccine plus 1 injection of placebo. Safety and tolerability will be evaluated by occurrence of adverse events, periodic laboratory tests, vital signs, and local/systemic reactogenicity. Comparison: Subjects will receive treatment with either HEPLISAV™ or the comparator vaccine, Engerix-B®.
Interventions
BIOLOGICALHEPLISAV and/or Placebo
Intramuscular (IM) injections on Week 0, Week 4; placebo (saline) injection at Week 24
BIOLOGICALEngerix-B
Intramuscular (IM) injections on Week 0, Week 4, and Week 24
Sponsors
Dynavax Technologies Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
11 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to give written informed consent * Is serum negative for HBV antibodies
Exclusion criteria
* Women who are pregnant or breastfeeding * Any previous HBV infection * Previous vaccination with any HBV vaccine (1 or more doses) * Any autoimmune disease * Received any blood products or antibodies within 3 months prior to study entry * Ever received an injection with DNA plasmids or oligonucleotides * Received any vaccines within 4 weeks prior to study entry * Received any other investigational medicinal agent within 4 weeks prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Seroprotective Immune Response | Week 12 for HEPLISAV and Week 28 for Engerix-B | Percentage of subjects who have a seroprotective immune response (anti-HBsAg ≥ 10 milli-international unit (mIU)/mL) after the final active injection in each treatment group (Week 12 for HEPLISAV™ and Week 28 for Engerix-B®) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Local and Systemic Reactions to Injections | Within 7 days post-injection for Post Injection Reactions |
Countries
Canada, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HEPLISAV and/or Placebo 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 | 1,821 |
| Engerix-B 1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24 | 607 |
| Total | 2,428 |
Baseline characteristics
| Characteristic | HEPLISAV and/or Placebo | Engerix-B | Total |
|---|---|---|---|
| Age, Customized 11 to 17 years | 11 Participants | 2 Participants | 13 Participants |
| Age, Customized ≥18 and ≤ 55 years | 1810 Participants | 605 Participants | 2415 Participants |
| Region of Enrollment Canada | 1123 Participants | 366 Participants | 1489 Participants |
| Region of Enrollment Germany | 698 Participants | 241 Participants | 939 Participants |
| Sex: Female, Male Female | 959 Participants | 346 Participants | 1305 Participants |
| Sex: Female, Male Male | 862 Participants | 261 Participants | 1123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 602 / 1,821 | 191 / 607 |
| serious Total, serious adverse events | 28 / 1,821 | 13 / 607 |
Outcome results
Primary
Percentage of Subjects With Seroprotective Immune Response
Percentage of subjects who have a seroprotective immune response (anti-HBsAg ≥ 10 milli-international unit (mIU)/mL) after the final active injection in each treatment group (Week 12 for HEPLISAV™ and Week 28 for Engerix-B®)
Time frame: Week 12 for HEPLISAV and Week 28 for Engerix-B
Population: Per Protocol Population: Subjects who met eligibility criteria, did not violate the protocol in a substantial manner, received all protocol-specified study injections, had their primary serology and all injections within the specified day ranges, and had serology at their primary endpoint (Week 12 for HEPLISAV group and Week 28 for Engerix-B group)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HEPLISAV and/or Placebo | Percentage of Subjects With Seroprotective Immune Response | 95.1 Percentage of Participants |
| Engerix-B | Percentage of Subjects With Seroprotective Immune Response | 81.3 Percentage of Participants |
Secondary
Percentage of Participants With Local and Systemic Reactions to Injections
Time frame: Within 7 days post-injection for Post Injection Reactions
Population: Safety Analysis Population: All participants who received at least 1 study injection and had any post-baseline data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 1 | 40.4 Percentage of subjects |
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 2 | 35.8 Percentage of subjects |
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 3 | 6.5 Percentage of subjects |
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 1 | 27.1 Percentage of subjects |
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 2 | 21.2 Percentage of subjects |
| HEPLISAV and/or Placebo | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 3 | 12.8 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 2 | 18.5 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 1 | 34.1 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 1 | 29.2 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 2 | 24.8 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Systemic Reaction : Injection 3 | 14.7 Percentage of subjects |
| Engerix-B | Percentage of Participants With Local and Systemic Reactions to Injections | Local Reaction : Injection 3 | 20.5 Percentage of subjects |