Hepatitis B
Conditions
Keywords
Sci-B-Vac, Prophylactic vaccine, Hepatitis B vaccines, Phase 3, pre-S1, pre-S2, Surface antigen, 3-antigen
Brief summary
This was a single-blind, 3-arm, comparative, controlled, randomized, study conducted at one site in Vietnam whose primary objective was to demonstrate clinical equivalence of the two production lots of Sci-B-Vac vaccine produced at two different facilities (OLD facility (Lot A) and NEW facility (Lot B) with respect to anti-hepatitis B-Surface (HBs) response. Secondary efficacy analysis was performed to demonstrate non-inferiority of seroprotection of each lot of Sci-B-Vac vaccine when compared to Engerix-B vaccine
Detailed description
This was a single-blind, 3-arm, comparative, controlled, randomized, study conducted at one site in Vietnam. Following a screening period, healthy eligible subjects (n = 402) were enrolled and randomized to receive Sci-B-Vac (OLD facility (Lot A) and NEW facility (Lot B), or Engerix-B. The study was conducted in two stages, approximately a year-and-a-half apart. In the first stage (Stage I) beginning in March 2006, Sci-B-Vac (Lot A) vaccine was compared to Engerix-B; and in the second stage (Stage II) beginning in November 2007, the Sci-B-Vac (Lot B) vaccine was compared to Engerix-B. The subjects assigned to the Engerix-B group were equally divided between the stages, 67 subjects in the Engerix-B group in Stages I and II, respectively, for a total of 134 subjects, such that the final number of randomized subjects in Stage 1 and Stage 2 across the Sci-B-Vac Lot A, Sci-B-Vac Lot B and Engerix-B was 1:1:1, respectively. Immunogenicity evaluations for Stage I data (Visits 5 and 6) were conducted together with Stage II data.
Interventions
BIOLOGICALSci-B-Vac-Lot B
Sci-B-Vac Lot B -10 μg of HBsAg, intramuscular injection of 10 μg/ml
BIOLOGICALSci-B-Vac-Lot A
Sci-B-Vac Lot A - 10 μg of HBsAg, intramuscular injection of 10 μg/ml
BIOLOGICALEngerix-B
Engerix-B (hepatitis B vaccine (recombinant)) is indicated for active immunization against hepatitis B virus infection
Sponsors
VBI Vaccines Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Intervention model description
Single blind, three-arm, two-stage, randomized study
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy adults 18 to 45 years of age who were seronegative for HBsAg, anti-HBs, anti-Hepatitis B core antigen, HIV, and Hepatitis C Virus (HCV)
Exclusion criteria
* Evidence of alcoholism or drug abuse, history of HIV, or HCV * Blood transfusions within the three months prior to inclusion in the study * Uncontrolled hypertension and other cardiovascular diseases * Chronic/concurrent administration (\>14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled and topical steroids were permitted * History of anaphylaxis (including shock) or any significant allergy or atopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination | Day 210 | Percentage of participants with an antibody response to hepatitis B surface antigens (anti-HBs), defined as an anti-HBs titer ≥10 IU/liter, one month after the third vaccination (Day 210) in the According-to-Protocol (ATP) population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Days 180, 210, and 360 | Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥10 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. |
| Anti-HBs Geometric Mean Concentration (GMC) | Days 180, 210, and 360 | Geometric mean concentration (GMC) of anti-HBs antibody just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. |
| Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Days 180, 210 and 360 | Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥100 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. |
Countries
Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sci-B-Vac-Lot B The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml | 131 |
| Engerix-B The mono-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials. | 133 |
| Sci-B-Vac-Lot A The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml | 134 |
| Total | 398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage I | Adverse Event | 0 | 0 | 3 |
| Stage I | Protocol Violation | 0 | 0 | 5 |
| Stage I | Withdrawal by Subject | 0 | 5 | 10 |
| Stage II | Adverse Event | 1 | 2 | 0 |
| Stage II | Moved from study area | 8 | 5 | 0 |
| Stage II | Protocol Violation | 1 | 2 | 0 |
| Stage II | Withdrawal by Subject | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Engerix-B | Total | Sci-B-Vac-Lot B | Sci-B-Vac-Lot A |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 133 Participants | 398 Participants | 131 Participants | 134 Participants |
| Age, Continuous | 20.48 years STANDARD_DEVIATION 1.655 | 20.62 years STANDARD_DEVIATION 1.913 | 20.58 years STANDARD_DEVIATION 1.577 | 20.79 years STANDARD_DEVIATION 2.392 |
| Body Mass Index | 20.0 kg/m^2 STANDARD_DEVIATION 2.2 | 20.3 kg/m^2 STANDARD_DEVIATION 1.9 | 20.1 kg/m^2 STANDARD_DEVIATION 1.5 | 20.9 kg/m^2 STANDARD_DEVIATION 1.9 |
| Ethnic Group Asian | 133 Participants | 398 Participants | 131 Participants | 134 Participants |
| Ethnic Group Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnic Group Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnic Group White/Caucasian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Vietnam | 133 Participants | 398 Participants | 131 Participants | 134 Participants |
| Sex: Female, Male Female | 89 Participants | 272 Participants | 94 Participants | 89 Participants |
| Sex: Female, Male Male | 44 Participants | 126 Participants | 37 Participants | 45 Participants |
| Smoking status Non-smoker | 127 Participants | 388 Participants | 128 Participants | 133 Participants |
| Smoking status Smoker | 6 Participants | 10 Participants | 3 Participants | 1 Participants |
| Weight | 50.2 kg STANDARD_DEVIATION 7.3 | 50.8 kg STANDARD_DEVIATION 6.5 | 50.2 kg STANDARD_DEVIATION 5.9 | 51.8 kg STANDARD_DEVIATION 6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 131 | 0 / 133 | 0 / 134 |
| other Total, other adverse events | 63 / 131 | 26 / 133 | 83 / 134 |
| serious Total, serious adverse events | 1 / 131 | 4 / 133 | 3 / 134 |
Outcome results
Primary
Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination
Percentage of participants with an antibody response to hepatitis B surface antigens (anti-HBs), defined as an anti-HBs titer ≥10 IU/liter, one month after the third vaccination (Day 210) in the According-to-Protocol (ATP) population.
Time frame: Day 210
Population: The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sci-B-Vac-Lot B | Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination | 120 Participants |
| Engerix-B | Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination | 115 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination | 109 Participants |
Secondary
Anti-HBs Geometric Mean Concentration (GMC)
Geometric mean concentration (GMC) of anti-HBs antibody just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population.
Time frame: Days 180, 210, and 360
Population: The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sci-B-Vac-Lot B | Anti-HBs Geometric Mean Concentration (GMC) | Day 210 | 12,158.94 IU/Liter |
| Sci-B-Vac-Lot B | Anti-HBs Geometric Mean Concentration (GMC) | Day 180 | 328.64 IU/Liter |
| Sci-B-Vac-Lot B | Anti-HBs Geometric Mean Concentration (GMC) | Day 360 | 3188.68 IU/Liter |
| Engerix-B | Anti-HBs Geometric Mean Concentration (GMC) | Day 210 | 4,124.24 IU/Liter |
| Engerix-B | Anti-HBs Geometric Mean Concentration (GMC) | Day 180 | 44.42 IU/Liter |
| Engerix-B | Anti-HBs Geometric Mean Concentration (GMC) | Day 360 | 991.07 IU/Liter |
| Sci-B-Vac-Lot A | Anti-HBs Geometric Mean Concentration (GMC) | Day 180 | 147.30 IU/Liter |
| Sci-B-Vac-Lot A | Anti-HBs Geometric Mean Concentration (GMC) | Day 360 | 1239.82 IU/Liter |
| Sci-B-Vac-Lot A | Anti-HBs Geometric Mean Concentration (GMC) | Day 210 | 3,587.30 IU/Liter |
Secondary
Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360.
Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥100 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population.
Time frame: Days 180, 210 and 360
Population: The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 210 | 118 Participants |
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 180 | 99 Participants |
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 360 | 113 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 210 | 113 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 180 | 40 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 360 | 100 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 180 | 68 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 360 | 94 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Day 210 | 106 Participants |
Secondary
Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360.
Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥10 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population.
Time frame: Days 180, 210, and 360
Population: The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 210 | 120 Participants |
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 180 | 118 Participants |
| Sci-B-Vac-Lot B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 360 | 115 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 210 | 115 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 180 | 95 Participants |
| Engerix-B | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 360 | 110 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 180 | 102 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 360 | 101 Participants |
| Sci-B-Vac-Lot A | Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Day 210 | 109 Participants |