Safety and Immunogenicity of Recombinant Hepatitis B Vaccine Sci-B-Vac® Compared to Engerix-B®

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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.

Official Title
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A Comparative Randomized Double-Blind Study of Safety and Immunogenicity of Recombinant Hepatitis B Vaccine Sci-B-Vac® in Adult Study Subjects

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Sci-B-Vac®
* Biological: Engerix-B®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Availability of written Informed Consent to participate in the study from the subject. Male or female between 18 and 45 years old without previous contact with hepatitis B virus (HBV). Good health condition based on full physical examination. Normal values of laboratory biochemical blood tests. Seronegative with respect to anti-HBs (surface) antibodies, anti-HBc (core) antibodies, and HBs Antigen (HBsAg) on screening. Not pregnant and not breast-feeding. 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: Congenital or inherited immunodeficiency disorder in family history. Information of a serious blood disorder, cardiac disorder, or tumour. Current use of any medication that could alter immune reactivity. Infection with HBV at the present time or in the past, confirmed by HBV markers test. Anaphylaxis or severe allergy, or atopy, history of alcoholism or drug abuse. Pregnancy and breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sci-B-Vac®<br>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. | Biological: Sci-B-Vac®<br>* Sci-B-Vac® vaccine-10 μg of HBsAg, intramuscular injection of 10 μg/ml<br>|
| Active Comparator: Engerix-B®<br>The single-antigen HepB vaccine, Engerix-B® (GSK), contains the small S recombinant protein. Engerix-B® was supplied in 1.0 ml vials. | Biological: Engerix-B®<br>* Engerix-B® vaccine-20 μg of HBsAg, intramuscular injection of 20 μg/ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sci-B-Vac®, Prophylactic vaccine, HepB vaccines, Phase 3, pre-S1, pre-S2, Surface antigen