Clinical trial NCT04209400: Safety and Immunogenicity of Recombinant Hepatitis B Vaccine Sci-B-Vac® Compared to Engerix-B®
Official title: A Comparative Randomized Double-Blind Study of Safety and Immunogenicity of Recombinant Hepatitis B Vaccine Sci-B-Vac® in Adult Study Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B
Keywords: Sci-B-Vac®
Prophylactic vaccine
HepB vaccines
Phase 3
pre-S1
pre-S2
Surface antigen
Lead sponsor: VBI Vaccines Inc.
Sponsor class: INDUSTRY
First posted: 2019-12-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Seroconversion Rate
timeFrame: Day 210
Secondary outcomes:
measure: Seroprotection Rate
timeFrame: Days 1, 28, 90, 180, 210
measure: Seroconversion Rate
timeFrame: Days 1, 28, 90, 180
measure: Geometric Mean Concentrations (GMC) of HBs Antibodies
timeFrame: Days 1, 28, 90, 180, and 210
Other outcomes:
measure: Adverse Events: Local Reactions at the Injection Site- Incidence of Redness
timeFrame: Day 1, Day 2, and Day 28
measure: Adverse Events: Local Reactions at the Injection Site - Incidence of Itch
timeFrame: Days 1-5, Days 28-32, Day 90, Days 180-185, Day 210
measure: Adverse Events: Local Reactions at the Injection Site - Incidence of Pain
timeFrame: Days 1, 28, 180
measure: Adverse Events: Local Reactions at the Injection Site - Intensity of Pain
timeFrame: Days 1, 28, 180
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Budgetary Healthcare Institution
state: Mirgorodskaya
Study officials:
affiliation: Saint Petersburg State Paediatric Medical University
name: Elena Esaulenko
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.