Hepatitis B Vaccines
Conditions
Keywords
Hepatitis B Vaccines
Brief summary
A Controlled Trial to Assess the Lot-to-lot Consistency of Sci-B-Vac™ in Adults
Detailed description
The primary objective of the study is to verify that the manufacturing equivalence of Sci-B-Vac™ is consistent and to compare the immunogenicity and safety of a three-dose regimen of Sci-B-Vac™ to a three-dose regimen of Engerix-B® in adults.
Interventions
BIOLOGICALHepatitis B Vaccination
Hepatitis B Vaccination
Sponsors
VBI Vaccines Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Double-blind Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Any gender * Age 18-45 years * Healthy, as determined by a physical examination and values of laboratory tests * If female, either is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), is of childbearing potential and must agree to use an adequate birth control method * Able and willing to give informed consent
Exclusion criteria
* Previous vaccination with any Hep B vaccine (HBV) (licensed or experimental) * Treatment by immunosuppressant within 30 days of enrollment * History of immunological function impairment * Pregnancy or breastfeeding * Immunization with attenuated vaccines (e.g. MMR) within 4 weeks prior to enrollment * Immunization with inactivated vaccines (e.g. influenza) within 2 week prior to enrolment * Has received blood products or immunoglobulin within 90 days of enrollment or is likely to require blood products during the study period * Subject in another clinical trial with an investigational drug or a biologic within 30 days of enrollment * Has received granulocyte-macrophage colony stimulating factor (G/GM-CSF) or erythropoietin (EPO) within 30 days of enrollment or likely to require GM-CSF or erythropoietin during the study period * Any history of cancer requiring chemotherapy or radiation within 5 years of randomization or current disease. * Any skin abnormality or tattoo that would limit post-vaccination injection site assessment * History of allergic reactions or anaphylactic reaction to any vaccine component * Unwilling, or unable in the opinion of the investigator, to comply with study requirements * Immediate family members of study center staff * Current or past hepatitis B infection or prior vaccination as evidenced by HBV markers * Known hepatitis C infection or positive Hepatitis C serology at screening, unless treated and cured * Known human immunodeficiency virus (HIV) infection or positive HIV serology at screening * Renal impairment with Glomerular Filtration Rate (GFR) \<90 mL/min/ 1.73 m2 at screening * BMI ≥ 35 * Uncontrolled hypertension * Diagnosis of Type 1 or Type 2 diabetes or HbA1C ≥ 6.5% at screening * Any laboratory test abnormality that would be considered of Grade 1 severity or above as per FDA guidelines for grading clinical laboratory abnormalities and is considered as clinically significant by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentration (GMC) of Anti-HBs at Day 196 for Lot-to-Lot Consistency (Per Protocol Set 1) | 4 weeks after third vaccination (Study Day 196) | To demonstrate the manufacturing equivalence, in terms of immunogenicity, as measured by GMC of antibodies, of 3 independent consecutive lots of the Sci-B-Vac® 4 weeks after the third vaccination. Lot-to-lot manufacturing consistency of Sci-B-Vac® is demonstrated if the 95% CIs of the adjusted anti-HBs GMC ratios between lots are within the pre-specified range of \[0.67, 1.5\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Rate (SPR) of Anti-HBs at Day 196 for Sci-B-Vac® Compared to Day 196 for Engerix-B® (Per Protocol Set 2) | 4 weeks after third vaccination (Study Day 196) | The difference in proportions \[SPR(Sci-B-Vac®)-SPR(Engerix-B®)\] and two-sided 95% CIs were summarized. If the lower bound of the 95% CI was \> 5%, Sci-B-Vac® was to be declared non-inferior to Engerix-B® |
| 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, Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Comparator: ENGERIX-B Hep B Vaccination Active Comparator: ENGERIX-B Hepatitis B Vaccination
Engerix-B® Hepatitis B Vaccination, 20ug, intramuscular (IM) injection at Days 0, 28, and 168. | 712 |
| Sci-B-Vac Lot A Hep B Vaccination Sci-B-Vac Lot A Hepatitis B Vaccination
Sci-B-Vac® Hepatitis B Vaccination, 10ug, intramuscular (IM) injection at Days 0, 28, and 168. | 711 |
| Sci-B-Vac Lot B Hep B Vaccination Sci-B-Vac Lot B Hepatitis B Vaccination
Sci-B-Vac® Hepatitis B Vaccination, 10ug, intramuscular (IM) injection at Days 0, 28, and 168. | 708 |
| Sci-B-Vac Lot C Hep B Vaccination Sci-B-Vac Lot C Hepatitis B Vaccination
Sci-B-Vac® Hepatitis B Vaccination, 10ug, intramuscular (IM) injection at Days 0, 28, and 168. | 705 |
| Total | 2,836 |
Baseline characteristics
| Characteristic | Sci-B-Vac Lot A Hep B Vaccination | Comparator: ENGERIX-B Hep B Vaccination | Sci-B-Vac Lot B Hep B Vaccination | Sci-B-Vac Lot C Hep B Vaccination | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 7.96 | 33.4 years STANDARD_DEVIATION 8.1 | 32.9 years STANDARD_DEVIATION 8 | 33.9 years STANDARD_DEVIATION 7.91 | 33.5 years STANDARD_DEVIATION 8 |
| BMI category <=30 kg/ m^2 | 576 Participants | 595 Participants | 591 Participants | 570 Participants | 2332 Participants |
| BMI category >30 kg/m^2 | 135 Participants | 117 Participants | 117 Participants | 135 Participants | 504 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 74 Participants | 70 Participants | 61 Participants | 269 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 643 Participants | 636 Participants | 638 Participants | 643 Participants | 2560 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Asian | 9 Participants | 9 Participants | 15 Participants | 13 Participants | 46 Participants |
| Race/Ethnicity, Customized Race Black or African American | 46 Participants | 38 Participants | 43 Participants | 34 Participants | 161 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 9 Participants | 8 Participants | 5 Participants | 26 Participants |
| Race/Ethnicity, Customized Race White | 650 Participants | 654 Participants | 641 Participants | 650 Participants | 2595 Participants |
| Region of Enrollment Canada | 31 participants | 31 participants | 29 participants | 30 participants | 121 participants |
| Region of Enrollment Europe | 489 participants | 493 participants | 493 participants | 490 participants | 1965 participants |
| Region of Enrollment United States | 191 participants | 188 participants | 186 participants | 185 participants | 750 participants |
| Sex: Female, Male Female | 408 Participants | 421 Participants | 395 Participants | 414 Participants | 1638 Participants |
| Sex: Female, Male Male | 303 Participants | 291 Participants | 313 Participants | 291 Participants | 1198 Participants |
| Smoking status Current smoker/ tobacco user | 139 Participants | 136 Participants | 142 Participants | 125 Participants | 542 Participants |
| Smoking status Former smoker/ tobacco user | 137 Participants | 141 Participants | 131 Participants | 136 Participants | 545 Participants |
| Smoking status Nonsmoker/ non-tobacco user | 435 Participants | 435 Participants | 435 Participants | 443 Participants | 1748 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 712 | 1 / 711 | 0 / 708 | 0 / 705 |
| other Total, other adverse events | 381 / 712 | 376 / 711 | 392 / 708 | 399 / 705 |
| serious Total, serious adverse events | 3 / 712 | 12 / 711 | 18 / 708 | 12 / 705 |
Outcome results
Primary
Geometric Mean Concentration (GMC) of Anti-HBs at Day 196 for Lot-to-Lot Consistency (Per Protocol Set 1)
To demonstrate the manufacturing equivalence, in terms of immunogenicity, as measured by GMC of antibodies, of 3 independent consecutive lots of the Sci-B-Vac® 4 weeks after the third vaccination. Lot-to-lot manufacturing consistency of Sci-B-Vac® is demonstrated if the 95% CIs of the adjusted anti-HBs GMC ratios between lots are within the pre-specified range of \[0.67, 1.5\].
Time frame: 4 weeks after third vaccination (Study Day 196)
Population: Per Protocol Set 1 included all subjects in the full analysis set who received all 3 vaccinations, had an evaluable serum immunogenicity samples at baseline and at the time point of interest, were seronegative at baseline, and had no major protocol violations leading to exclusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sci-B-Vac Lot A Hep B Vaccination | Geometric Mean Concentration (GMC) of Anti-HBs at Day 196 for Lot-to-Lot Consistency (Per Protocol Set 1) | 5883.93 mIU/ml | Standard Deviation 5.423 |
| Sci-B-Vac Lot B Hep B Vaccination | Geometric Mean Concentration (GMC) of Anti-HBs at Day 196 for Lot-to-Lot Consistency (Per Protocol Set 1) | 4824.06 mIU/ml | Standard Deviation 6.293 |
| Sci-B-Vac Lot C Hep B Vaccination | Geometric Mean Concentration (GMC) of Anti-HBs at Day 196 for Lot-to-Lot Consistency (Per Protocol Set 1) | 5505.98 mIU/ml | Standard Deviation 5.975 |
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 included all subjects in the All Enrolled Set who received at least 1 vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 384 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 391 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritis/itching | 88 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 12 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 6 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 86 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 105 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 268 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 284 Participants |
| Sci-B-Vac Lot A Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 231 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritis/itching | 84 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 266 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 27 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 18 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 85 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 94 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 289 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 255 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 527 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 519 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 275 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 87 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 316 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 536 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 20 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 87 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 296 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 535 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 15 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritis/itching | 105 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Swelling/edema | 22 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 281 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea/vomiting | 79 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 337 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Diarrhea | 96 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Tenderness | 541 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pruritis/itching | 92 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Redness/erythema | 14 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Pain | 542 Participants |
| Sci-B-Vac Lot C Hep B Vaccination | Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 290 Participants |
Secondary
Seroprotection Rate (SPR) of Anti-HBs at Day 196 for Sci-B-Vac® Compared to Day 196 for Engerix-B® (Per Protocol Set 2)
The difference in proportions \[SPR(Sci-B-Vac®)-SPR(Engerix-B®)\] and two-sided 95% CIs were summarized. If the lower bound of the 95% CI was \> 5%, Sci-B-Vac® was to be declared non-inferior to Engerix-B®
Time frame: 4 weeks after third vaccination (Study Day 196)
Population: Per Protocol Set 2 included all subjects in Per Protocol Set 1 excluding subjects who attended visits outside of windows including Visit 3/Day 168 (±28 days) and Visit 44/Day 196 (-7/+14 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sci-B-Vac Lot A Hep B Vaccination | Seroprotection Rate (SPR) of Anti-HBs at Day 196 for Sci-B-Vac® Compared to Day 196 for Engerix-B® (Per Protocol Set 2) | 561 Participants |
| Sci-B-Vac Lot B Hep B Vaccination | Seroprotection Rate (SPR) of Anti-HBs at Day 196 for Sci-B-Vac® Compared to Day 196 for Engerix-B® (Per Protocol Set 2) | 1740 Participants |