Trial Outcomes & Findings for Safety and Efficacy of HEPLISAV™ Hepatitis B Virus Vaccine Compared With Engerix-B® Vaccine (NCT NCT00435812)
NCT ID: NCT00435812
Last Updated: 2019-03-20
Results Overview
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®)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
2428 participants
Primary outcome timeframe
Week 12 for HEPLISAV and Week 28 for Engerix-B
Results posted on
2019-03-20
Participant Flow
Participant milestones
| Measure |
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 and Week 4, plus a placebo (saline) injection at Week 24
|
Engerix-B
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
|---|---|---|
|
Overall Study
STARTED
|
1820
|
608
|
|
Overall Study
COMPLETED
|
1757
|
590
|
|
Overall Study
NOT COMPLETED
|
63
|
18
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy of HEPLISAV™ Hepatitis B Virus Vaccine Compared With Engerix-B® Vaccine
Baseline characteristics by cohort
| Measure |
HEPLISAV and/or Placebo
n=1821 Participants
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
|
Engerix-B
n=607 Participants
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
Total
n=2428 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
11 to 17 years
|
11 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Customized
≥18 and ≤ 55 years
|
1810 Participants
n=5 Participants
|
605 Participants
n=7 Participants
|
2415 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
959 Participants
n=5 Participants
|
346 Participants
n=7 Participants
|
1305 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
862 Participants
n=5 Participants
|
261 Participants
n=7 Participants
|
1123 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1123 Participants
n=5 Participants
|
366 Participants
n=7 Participants
|
1489 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
698 Participants
n=5 Participants
|
241 Participants
n=7 Participants
|
939 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12 for HEPLISAV and Week 28 for Engerix-BPopulation: 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)
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®)
Outcome measures
| Measure |
HEPLISAV and/or Placebo
n=1520 Participants
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
|
Engerix-B
n=523 Participants
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
|---|---|---|
|
Percentage of Subjects With Seroprotective Immune Response
|
95.1 Percentage of Participants
|
81.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Within 7 days post-injection for Post Injection ReactionsPopulation: Safety Analysis Population: All participants who received at least 1 study injection and had any post-baseline data.
Outcome measures
| Measure |
HEPLISAV and/or Placebo
n=1821 Participants
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
|
Engerix-B
n=607 Participants
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
|---|---|---|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Systemic Reaction : Injection 2
|
21.2 Percentage of subjects
|
18.5 Percentage of subjects
|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Systemic Reaction : Injection 3
|
12.8 Percentage of subjects
|
14.7 Percentage of subjects
|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Local Reaction : Injection 1
|
40.4 Percentage of subjects
|
34.1 Percentage of subjects
|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Local Reaction : Injection 2
|
35.8 Percentage of subjects
|
24.8 Percentage of subjects
|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Local Reaction : Injection 3
|
6.5 Percentage of subjects
|
20.5 Percentage of subjects
|
|
Percentage of Participants With Local and Systemic Reactions to Injections
Systemic Reaction : Injection 1
|
27.1 Percentage of subjects
|
29.2 Percentage of subjects
|
Adverse Events
HEPLISAV and/or Placebo
Serious events: 28 serious events
Other events: 602 other events
Deaths: 0 deaths
Engerix-B
Serious events: 13 serious events
Other events: 191 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HEPLISAV and/or Placebo
n=1821 participants at risk
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
|
Engerix-B
n=607 participants at risk
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Gastrointestinal disorders
Gastritis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
General disorders
Device dislocation
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Infections and infestations
Liver abscess
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Infections and infestations
Salpingo-oophoritis
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Infections and infestations
Septic shock
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Infections and infestations
Tonsillitis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
0.11%
2/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Sternal fracture
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Musculoskeletal and connective tissue disorders
Gouty arthritis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.11%
2/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer recurrent
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Nervous system disorders
Cerebral ischaemia
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Nervous system disorders
Guillain-barre syndrome
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Psychiatric disorders
Delirium tremens
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Psychiatric disorders
Depression
|
0.11%
2/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Renal and urinary disorders
Renal failure
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Reproductive system and breast disorders
Prostatitis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.16%
1/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.16%
3/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Vascular disorders
Granulomatosis with polyangiitis
|
0.05%
1/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
0.00%
0/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
Other adverse events
| Measure |
HEPLISAV and/or Placebo
n=1821 participants at risk
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
|
Engerix-B
n=607 participants at risk
1.0 mL Engerix-B
Engerix-B: Intramuscular (IM) injections on Week 0, Week 4, and Week 24
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
16.6%
303/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
16.5%
100/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.2%
94/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
4.8%
29/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
|
Nervous system disorders
Headache
|
11.3%
205/1821
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
10.2%
62/607
Adverse events were assessed for safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
|
Additional Information
Robert Janssen MD \ VP & Chief Medical Officer
Dynavax Technologies, Inc.
Phone: 510-848-5100
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60