Hepatitis B
Conditions
Keywords
Sci-B-Vac®, Prophylactic vaccine, HepB vaccines, Phase 3, pre-S1, pre-S2, Surface antigen
Brief summary
This study was a comparative, randomized, double-blind clinical study of the efficacy and safety of Sci-B-Vac® (10 μg dose) and the Engerix-B® (20 μg dose) vaccines in two parallel groups of hepatitis B-naive healthy adult subjects in Russia.
Detailed description
This study was a comparative randomized double-blind clinical study of the efficacy and safety of Sci-B-Vac® (10 μg dose) and the Engerix-B® (20 μg dose) vaccines in hepatitis B-naive healthy adult subjects (n = 100). The study was conducted at 3 study sites in the Russian Federation. Subjects who passed the screening successfully were randomized into two groups, Sci-B-Vac® (10 μg dose) and Engerix-B® (20 μg dose), in a 1:1 ratio. Subjects were vaccinated three times at days 1, 28, and 180 of the study. Statistical Methods: Evaluation and comparison of immunogenicity were conducted at baseline, day 28, day 90 (60 days after the second vaccination), day 180 (prior to administering the third vaccine, 90 days after the second vaccination), and day 210 (30 days after the third vaccination) of the study. The primary outcome was the seroconversion rate (proportion of subjects with anti-HBs levels ≥ 2.1 mIU/mL) after the third vaccination at day 210. The non-inferiority margin was set at 4%. The percentage of subjects who achieved seroconversion was analyzed using the Chi-square test for proportions along with the McNemar's test for repeated measurements in each group. The non-inferiority hypotheses were confirmed if the lower range of the confidence interval was at least -4%. The secondary endpoint was SPR (≥10 mIU/ml), measured at days 1, 28, 90, 180 and 210. Demographic data, initial parameters, safety parameters, tolerance of the experimental vaccine, and other study parameters were analyzed using descriptive statistics (mean value, standard deviation, median, minimum and maximum values, range, quartiles, the number of valid cases-for quantitative variables; absolute number, proportion, allocation-for qualitative variables). A comparative assessment of the detection rate for different parameters in the two comparison groups was conducted using the Student's t-test; differences were considered statistically significant at a significance level of 5%. The assay used to measure anti-HBs concentrations had an upper limit of 1000 mIU/mL.
Interventions
BIOLOGICALSci-B-Vac®
Sci-B-Vac® vaccine-10 μg of HBsAg, intramuscular injection of 10 μg/ml
BIOLOGICALEngerix-B®
Engerix-B® vaccine-20 μg of HBsAg, intramuscular injection of 20 μg/ml
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 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Availability of written Informed Consent to participate in the study from the subject. 2. Male or female between 18 and 45 years old without previous contact with hepatitis B virus (HBV). 3. Good health condition based on full physical examination. 4. Normal values of laboratory biochemical blood tests. 5. Seronegative with respect to anti-HBs (surface) antibodies, anti-HBc (core) antibodies, and HBs Antigen (HBsAg) on screening. 6. Not pregnant and not breast-feeding. 7. For men and women of reproductive age: consent for use of an effective contraception method, for example, an intrauterine device, oral contraceptive, hypodermic implant or double barrier method (a condom with contraceptive sponge or contraceptive suppository) throughout the entire study.
Exclusion criteria
1. Congenital or inherited immunodeficiency disorder in family history. 2. Information of a serious blood disorder, cardiac disorder, or tumour. 3. Current use of any medication that could alter immune reactivity. 4. Infection with HBV at the present time or in the past, confirmed by HBV markers test. 5. Anaphylaxis or severe allergy, or atopy, history of alcoholism or drug abuse. 6. Pregnancy and breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate | Day 210 | Percentage of subjects with an anti-HBs antibody level ≥ 2.1 mIU/mL 30 days after the last of three vaccinations. Seroconversion is defined as the development of a detectable anti-HBs antibody level above an established threshold of 2.1 mIU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Rate | Days 1, 28, 90, 180, 210 | Percentage of subjects with an anti-HBs antibody level ≥ 10 mIU/mL prior to vaccination, 28 days after the first vaccination, 60 and 150 days after the second vaccination and 30 days after the third vaccination. The development of an anti-HBs antibody level of at least 10 mIU/mL is an established surrogate of seroprotection and correlate of protective immunity against HBV. |
| Seroconversion Rate | Days 1, 28, 90, 180 | Percentage of subjects with an anti-HBs antibody level ≥ 2.1 mIU/mL prior to vaccination, 28 days after the first vaccination and 60 and 150 days after the second vaccination. Seroconversion is defined as the development of a detectable anti-HBs antibody level above an established threshold of 2.1 mIU/mL. |
| Geometric Mean Concentrations (GMC) of HBs Antibodies | Days 1, 28, 90, 180, and 210 | Geometric mean concentration of anti-HBs antibody in mIU/mL 28 days after the first vaccination, 60 and 150 days after the second vaccination, and 30 days after the third vaccination. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 1, Day 2, and Day 28 | Incidence of mild erythema at the injection site 1, 2 and 28 days after the first vaccination. |
| Adverse Events: Local Reactions at the Injection Site - Incidence of Itch | Days 1-5, Days 28-32, Day 90, Days 180-185, Day 210 | Incidence of itchiness at the injection site at any point throughout the trial. Itchiness was assessed for 5 days following vaccinations on Days 1, 28, and 180 and also assessed on Day 90 and Day 210. |
| Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Days 1, 28, 180 | Incidence of pain at the injection site on the day of vaccination. Vaccination was performed on Day 1, Day 28, and Day 180. |
| Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Days 1, 28, 180 | Pain was evaluated 30 minutes after each vaccination by the subject using the visual analogue scale. A higher score indicates greater pain intensity. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sci-B-Vac® Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 180.
Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination | 50 |
| Engerix-B® Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 180.
Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Sci-B-Vac® | Engerix-B® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 50 Participants | 100 Participants |
| Age, Continuous | 28.38 years STANDARD_DEVIATION 7.72 | 30.56 years STANDARD_DEVIATION 8.13 | 29.47 years STANDARD_DEVIATION 7.96 |
| Race/Ethnicity, Customized Caucasian-Russians | 50 Participants | 50 Participants | 100 Participants |
| Region of Enrollment Russia | 50 Participants | 50 Participants | 100 Participants |
| Sex: Female, Male Female | 32 Participants | 29 Participants | 61 Participants |
| Sex: Female, Male Male | 18 Participants | 21 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 49 |
| other Total, other adverse events | 2 / 50 | 7 / 49 |
| serious Total, serious adverse events | 0 / 50 | 0 / 49 |
Outcome results
Primary
Seroconversion Rate
Percentage of subjects with an anti-HBs antibody level ≥ 2.1 mIU/mL 30 days after the last of three vaccinations. Seroconversion is defined as the development of a detectable anti-HBs antibody level above an established threshold of 2.1 mIU/mL.
Time frame: Day 210
Population: The primary analysis was performed on the intent-to-treat (ITT) set, which included all participants randomized. Analysis of the study parameters for vaccine immunogenicity was performed for all subjects included in the vaccine groups who received at least one injection, if at least one assessment after the start of the vaccination was available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sci-B-Vac® | Seroconversion Rate | 47 Participants |
| Engerix-B® | Seroconversion Rate | 46 Participants |
Comparison: The null hypothesis is that the vaccines equally affect the achievement of seroconversion level.p-value: 1Chi-squared
Secondary
Geometric Mean Concentrations (GMC) of HBs Antibodies
Geometric mean concentration of anti-HBs antibody in mIU/mL 28 days after the first vaccination, 60 and 150 days after the second vaccination, and 30 days after the third vaccination.
Time frame: Days 1, 28, 90, 180, and 210
Population: The analysis was performed on the intent-to-treat (ITT) set, which included all participants randomized. Analysis of the study parameters for vaccine immunogenicity was performed for all subjects included in the vaccine groups who received at least one injection, if at least one assessment after the start of the vaccination was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sci-B-Vac® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 180 | 757.7 mIU/mL | Standard Deviation 378 |
| Sci-B-Vac® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 210 | 891.4 mIU/mL | Standard Deviation 253.7 |
| Sci-B-Vac® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 90 | 618.3 mIU/mL | Standard Deviation 404.2 |
| Engerix-B® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 180 | 441.3 mIU/mL | Standard Deviation 437.6 |
| Engerix-B® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 210 | 787.0 mIU/mL | Standard Deviation 351.9 |
| Engerix-B® | Geometric Mean Concentrations (GMC) of HBs Antibodies | Day 90 | 378.7 mIU/mL | Standard Deviation 417.9 |
Secondary
Seroconversion Rate
Percentage of subjects with an anti-HBs antibody level ≥ 2.1 mIU/mL prior to vaccination, 28 days after the first vaccination and 60 and 150 days after the second vaccination. Seroconversion is defined as the development of a detectable anti-HBs antibody level above an established threshold of 2.1 mIU/mL.
Time frame: Days 1, 28, 90, 180
Population: The analysis was performed on the intent-to-treat (ITT) set, which included all participants randomized. Analysis of the study parameters for vaccine immunogenicity was performed for all subjects included in the vaccine groups who received at least one injection, if at least one assessment after the start of the vaccination was available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac® | Seroconversion Rate | Day 1 | 0 Participants |
| Sci-B-Vac® | Seroconversion Rate | Day 28 | 46 Participants |
| Sci-B-Vac® | Seroconversion Rate | Day 90 | 48 Participants |
| Sci-B-Vac® | Seroconversion Rate | Day 180 | 47 Participants |
| Engerix-B® | Seroconversion Rate | Day 180 | 45 Participants |
| Engerix-B® | Seroconversion Rate | Day 1 | 0 Participants |
| Engerix-B® | Seroconversion Rate | Day 90 | 45 Participants |
| Engerix-B® | Seroconversion Rate | Day 28 | 36 Participants |
Secondary
Seroprotection Rate
Percentage of subjects with an anti-HBs antibody level ≥ 10 mIU/mL prior to vaccination, 28 days after the first vaccination, 60 and 150 days after the second vaccination and 30 days after the third vaccination. The development of an anti-HBs antibody level of at least 10 mIU/mL is an established surrogate of seroprotection and correlate of protective immunity against HBV.
Time frame: Days 1, 28, 90, 180, 210
Population: The analysis was performed on the intent-to-treat (ITT) set, which included all participants randomized. Analysis of the study parameters for vaccine immunogenicity was performed for all subjects included in the vaccine groups who received at least one injection, if at least one assessment after the start of the vaccination was available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac® | Seroprotection Rate | Day 1 | 0 Participants |
| Sci-B-Vac® | Seroprotection Rate | Day 180 | 47 Participants |
| Sci-B-Vac® | Seroprotection Rate | Day 28 | 30 Participants |
| Sci-B-Vac® | Seroprotection Rate | Day 90 | 47 Participants |
| Engerix-B® | Seroprotection Rate | Day 28 | 24 Participants |
| Engerix-B® | Seroprotection Rate | Day 90 | 41 Participants |
| Engerix-B® | Seroprotection Rate | Day 1 | 0 Participants |
| Engerix-B® | Seroprotection Rate | Day 180 | 42 Participants |
Other Pre-specified
Adverse Events: Local Reactions at the Injection Site - Incidence of Itch
Incidence of itchiness at the injection site at any point throughout the trial. Itchiness was assessed for 5 days following vaccinations on Days 1, 28, and 180 and also assessed on Day 90 and Day 210.
Time frame: Days 1-5, Days 28-32, Day 90, Days 180-185, Day 210
Population: The analysis of safety and tolerability was conducted in the population of subjects included in the study meeting the inclusion criteria while complying with the exclusion criteria, who received at least one dose of the experimental vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Incidence of Itch | 1 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Incidence of Itch | 0 Participants |
Other Pre-specified
Adverse Events: Local Reactions at the Injection Site - Incidence of Pain
Incidence of pain at the injection site on the day of vaccination. Vaccination was performed on Day 1, Day 28, and Day 180.
Time frame: Days 1, 28, 180
Population: The analysis of safety and tolerability was conducted in the population of subjects included in the study meeting the inclusion criteria while complying with the exclusion criteria, who received at least one dose of the experimental vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 1 | 7 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 28 | 8 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 180 | 7 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 1 | 8 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 28 | 7 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Incidence of Pain | Day 180 | 11 Participants |
Other Pre-specified
Adverse Events: Local Reactions at the Injection Site- Incidence of Redness
Incidence of mild erythema at the injection site 1, 2 and 28 days after the first vaccination.
Time frame: Day 1, Day 2, and Day 28
Population: The analysis of safety and tolerability was conducted in the population of subjects included in the study meeting the inclusion criteria while complying with the exclusion criteria, who received at least one dose of the experimental vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 1 | 8 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 2 | 2 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 28 | 3 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 1 | 4 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 2 | 1 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site- Incidence of Redness | Day 28 | 0 Participants |
Other Pre-specified
Adverse Events: Local Reactions at the Injection Site - Intensity of Pain
Pain was evaluated 30 minutes after each vaccination by the subject using the visual analogue scale. A higher score indicates greater pain intensity.
Time frame: Days 1, 28, 180
Population: The analysis of safety and tolerability was conducted in the population of subjects included in the study meeting the inclusion criteria while complying with the exclusion criteria, who received at least one dose of the experimental vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pains score 1 | 43 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 2 | 7 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 2 | 7 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 3 | 1 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pain score 3 | 2 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 1 | 40 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 1 | 42 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 3 | 0 Participants |
| Sci-B-Vac® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pain score 2 | 5 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 3 | 2 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pain score 2 | 6 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 2 | 9 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pains score 1 | 41 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 1 : Pain score 3 | 2 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 1 | 41 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 2 | 6 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 28 : Pain score 3 | 1 Participants |
| Engerix-B® | Adverse Events: Local Reactions at the Injection Site - Intensity of Pain | Day 180 : Pain score 1 | 36 Participants |