Hepatitis B Vaccines
Conditions
Keywords
Hepatitis B Vaccines
Brief summary
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in ≥ 45 years old.
Detailed description
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 45 years old. Study subjects are randomized 1:1 to receive either a total of 3 injections of Sci-B-Vac® or 3 injections of Engerix-B® intra-muscularly (IM) on Days 0, 28, and 168.
Interventions
BIOLOGICALHepatitis B Vaccination
Prophylactic Hepatitis B Vaccination
Sponsors
VBI Vaccines Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Any gender. * Age ≥ 18 years * In stable health as determined by a physical examination and laboratory tests values. Common chronic conditions such as, but not limited to, type 2 diabetes, high blood pressure, Chronic Obstructive Pulmonary Disease (COPD) and asthma will be accepted if the condition is well controlled, as determined by the investigator, and not meeting the
Exclusion criteria
. For subjects \> 65 years old, Frailty Index ≤3 * If female, either is not of childbearing potential or is of childbearing potential and must agree to use an adequate birth control method during the screening period and until the end of her participation in the study * Able and willing to give consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | Day 196 | To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is non-inferior to a three-dose regimen of Engerix-B® in adults ≥18 years old; i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after the third vaccination, will be \> - 5%. |
| Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | Day 196 | To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be \> 5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Day of vaccine administration and six subsequent days | Analysis of local and systemic solicited adverse events with an interval of onset of Day 1 to Day 7 after any vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old. |
Countries
Belgium, Canada, Finland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engerix-B® Hepatitis B Vaccination Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168.
Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination | 811 |
| Sci-B-Vac® Hepatitis B Vaccination Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168.
Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination | 796 |
| Total | 1,607 |
Baseline characteristics
| Characteristic | Engerix-B® Hepatitis B Vaccination | Sci-B-Vac® Hepatitis B Vaccination | Total |
|---|---|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 13.46 | 56.6 years STANDARD_DEVIATION 13.2 | 56.6 years STANDARD_DEVIATION 58 |
| Age, Customized 18-44 years | 154 Participants | 145 Participants | 299 Participants |
| Age, Customized 45-64 years | 361 Participants | 355 Participants | 716 Participants |
| Age, Customized ≥ 65 years | 296 Participants | 296 Participants | 592 Participants |
| BMI category <=30 kg/m^2 | 519 Participants | 499 Participants | 1018 Participants |
| BMI category >30 kg/m^2 | 292 Participants | 297 Participants | 589 Participants |
| Diabetes status Diabetic | 65 Participants | 60 Participants | 125 Participants |
| Diabetes status Non-diabetic | 746 Participants | 736 Participants | 1482 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 75 Participants | 79 Participants | 154 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 732 Participants | 714 Participants | 1446 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 65 Participants | 66 Participants | 131 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 730 Participants | 715 Participants | 1445 Participants |
| Region of Enrollment Canada | 133 participants | 126 participants | 259 participants |
| Region of Enrollment Europe | 336 participants | 332 participants | 668 participants |
| Region of Enrollment United States | 342 participants | 338 participants | 680 participants |
| Sex: Female, Male Female | 508 Participants | 481 Participants | 989 Participants |
| Sex: Female, Male Male | 303 Participants | 315 Participants | 618 Participants |
| Smoking status/Tobacco use Current smoker/tobacco user | 113 Participants | 104 Participants | 217 Participants |
| Smoking status/Tobacco use Former smoker/tobacco user | 224 Participants | 203 Participants | 427 Participants |
| Smoking status/Tobacco use Non-smoker/non-tobacco user | 474 Participants | 489 Participants | 963 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 811 | 0 / 796 |
| other Total, other adverse events | 455 / 811 | 429 / 796 |
| serious Total, serious adverse events | 21 / 811 | 32 / 796 |
Outcome results
Primary
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is non-inferior to a three-dose regimen of Engerix-B® in adults ≥18 years old; i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after the third vaccination, will be \> - 5%.
Time frame: Day 196
Population: Per-protocol set - all subjects in the full analysis set who received all 3 injections, had at least baseline and 1 post-baseline immunogenicity assessment (at the time point of interest), were seronegative at baseline, and had no major protocol deviations leading to exclusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B® Hepatitis B Vaccination | Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | 76.49 percentage of participants seroprotected |
| Sci-B-Vac® Hepatitis B Vaccination | Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | 91.36 percentage of participants seroprotected |
Primary
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be \> 5%.
Time frame: Day 196
Population: Full analysis set - subjects who received at least 1 injection and had at least baseline and 1 post baseline immunogenicity assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B® Hepatitis B Vaccination | Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | 73.05 percentage of participants seroprotected |
| Sci-B-Vac® Hepatitis B Vaccination | Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 | 89.44 percentage of participants seroprotected |
Secondary
Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs)
Analysis of local and systemic solicited adverse events with an interval of onset of Day 1 to Day 7 after any vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.
Time frame: Day of vaccine administration and six subsequent days
Population: Safety set: all subjects in the All Enrolled Set who received at least 1 injection
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritus/itching | 66 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 249 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 282 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 238 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 15 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 197 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 294 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 96 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 12 Participants |
| Engerix-B® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 73 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 18 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 503 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 484 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritus/itching | 76 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 18 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 56 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 242 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 249 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 276 Participants |
| Sci-B-Vac® Hepatitis B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 82 Participants |