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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Sci-B-Vac®; Biological: Engerix-B®

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Mirgorodskaya
    • Saint Petersburg, Mirgorodskaya, Russian Federation, 191167
      • Saint Petersburg State Budgetary Healthcare Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sci-B-Vac®; 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®; Sci-B-Vac® vaccine-10 μg of HBsAg, intramuscular injection of 10 μg/ml
Active Comparator: Engerix-B®; 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®; Engerix-B® vaccine-20 μg of HBsAg, intramuscular injection of 20 μg/ml

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: VBI Vaccines Inc.
• Investigators: Principal Investigator: Elena Esaulenko, Saint Petersburg State Paediatric Medical University

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to full length manuscript

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2014
• Primary Completion (Actual): April 20, 2015
• Study Completion (Actual): April 20, 2015

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Phase 3; Sci-B-Vac®; Prophylactic vaccine; HepB vaccines; pre-S1; pre-S2; Surface antigen
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: 38-13-040 RUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No