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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sci-B-Vac® | Experimental | The 3-antigen HepB vaccine, Sci-B-Vac® contains three recombinant proteins of HBV viral envelope: small S, medium pre-S2, and large pre-S1 surface antigens. Sci-B-Vac® was supplied in 1.0 ml vials. |
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| Engerix-B® | Active Comparator | The single-antigen HepB vaccine, Engerix-B® (GSK), contains the small S recombinant protein. Engerix-B® was supplied in 1.0 ml vials. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sci-B-Vac® | Biological | Sci-B-Vac® vaccine-10 μg of HBsAg, intramuscular injection of 10 μg/ml |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 210 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Days 1, 28, 90, 180, 210 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1, Day 2, and Day 28 |
| Adverse Events: Local Reactions at the Injection Site - Incidence of Itch |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elena Esaulenko | Saint Petersburg State Paediatric Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Saint Petersburg State Budgetary Healthcare Institution | Saint Petersburg | Mirgorodskaya | 191167 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33119068 | Result | Esaulenko EV, Yakovlev AA, Volkov GA, Sukhoruk AA, Surkov KG, Kruglyakov PV, Diaz-Mitoma F. Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation. Clin Infect Dis. 2021 Nov 2;73(9):e3333-e3339. doi: 10.1093/cid/ciaa1649. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sci-B-Vac® | Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 1, 28 and 180 Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Engerix-B® |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Count of Participants | Participants | Day 210 |
|
Through study completion, approximately 7 months.
An AE is any unfavourable sign (including abnormal lab results), symptom, or disease that are time-associated with vaccine use, regardless whether or not they are viewed as having been caused by medicinal products, and whether they are mild or serious. Intensity of the adverse events were defined as Mild: Adverse event that is easily tolerated. Moderate: AEs causing discomfort sufficient for impairment of everyday activity. Severe: Adverse event preventing normal everyday activity
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sci-B-Vac® | Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, intramuscular (IM) injection at Days 0, 28, and 180. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperthermia | General disorders | MedDRA | Non-systematic Assessment |
Final CSR does not follow ICH guidelines and the original document in Russian was translated into English for the purpose of writing the manuscript and completing the documentation in clinicaltrials.gov
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Francisco Diaz-Mitoma | VBI Vaccines Inc. | 613-297-3304 | fdiazmitoma@vbivaccines.com |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| ID | Term |
|---|---|
| C000608755 | Pre-S vaccine |
| C075654 | Engerix-B |
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| Engerix-B® | Biological | Engerix-B® vaccine-20 μg of HBsAg, intramuscular injection of 20 μg/ml |
|
| 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. | Days 1, 28, 90, 180 |
| 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. | Days 1, 28, 90, 180, and 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. |
| Days 1-5, Days 28-32, Day 90, Days 180-185, Day 210 |
| 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. | Days 1, 28, 180 |
| 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. | Days 1, 28, 180 |
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
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Engerix-B® | Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, intramuscular (IM) injection at Days 0, 28, and 180. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination |
|
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| 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. | 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. | Posted | Count of Participants | Participants | Days 1, 28, 90, 180, 210 |
|
|
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| 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. | 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. | Posted | Count of Participants | Participants | Days 1, 28, 90, 180 |
|
|
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| 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. | 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. | Posted | Mean | Standard Deviation | mIU/mL | Days 1, 28, 90, 180, and 210 |
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| 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. | 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. | Posted | Count of Participants | Participants | Day 1, Day 2, and Day 28 |
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| 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. | 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. | Posted | Count of Participants | Participants | Days 1-5, Days 28-32, Day 90, Days 180-185, Day 210 |
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| 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. | 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. | Posted | Count of Participants | Participants | Days 1, 28, 180 |
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| 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. | 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. | Posted | Count of Participants | Participants | Days 1, 28, 180 |
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| 0 |
| 50 |
| 0 |
| 50 |
| 2 |
| 50 |
| EG001 | Engerix-B® | Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, intramuscular (IM) injection at Days 0, 28, and 180. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination | 0 | 49 | 0 | 49 | 7 | 49 |
| drowsiness | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| nausea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
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| metallic taste | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| acute respiratory viral infection | Infections and infestations | MedDRA | Non-systematic Assessment |
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| rotavirus infection | Infections and infestations | MedDRA | Non-systematic Assessment |
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| steatohepatitis | Hepatobiliary disorders | MedDRA | Non-systematic Assessment |
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| weakness | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
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| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| Day 28 |
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| Day 90 |
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| Day 180 |
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| Day 28 |
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| Day 90 |
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| Day 180 |
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| Day 210 |
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| Day 28 |
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| Day 180 |
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| Day 1 : Pain score 2 |
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| Day 1 : Pain score 3 |
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| Day 28 : Pain score 1 |
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| Day 28 : Pain score 2 |
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| Day 28 : Pain score 3 |
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| Day 180 : Pain score 1 |
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| Day 180 : Pain score 2 |
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| Day 180 : Pain score 3 |
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