A Bridging Study: Comparing Two Lots of Sci-B-Vac™ and Engerix-B in Healthy Adults

Study Overview
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Brief Summary
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This was a single-blind, 3-arm, comparative, controlled, randomized, study conducted at one site in Vietnam whose primary objective was to demonstrate clinical equivalence of the two production lots of Sci-B-Vac vaccine produced at two different facilities (OLD facility (Lot A) and NEW facility (Lot B) with respect to anti-hepatitis B-Surface (HBs) response. Secondary efficacy analysis was performed to demonstrate non-inferiority of seroprotection of each lot of Sci-B-Vac vaccine when compared to Engerix-B vaccine

Detailed Description
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This was a single-blind, 3-arm, comparative, controlled, randomized, study conducted at one site in Vietnam. Following a screening period, healthy eligible subjects (n = 402) were enrolled and randomized to receive Sci-B-Vac (OLD facility (Lot A) and NEW facility (Lot B), or Engerix-B. The study was conducted in two stages, approximately a year-and-a-half apart. In the first stage (Stage I) beginning in March 2006, Sci-B-Vac (Lot A) vaccine was compared to Engerix-B; and in the second stage (Stage II) beginning in November 2007, the Sci-B-Vac (Lot B) vaccine was compared to Engerix-B. The subjects assigned to the Engerix-B group were equally divided between the stages, 67 subjects in the Engerix-B group in Stages I and II, respectively, for a total of 134 subjects, such that the final number of randomized subjects in Stage 1 and Stage 2 across the Sci-B-Vac Lot A, Sci-B-Vac Lot B and Engerix-B was 1:1:1, respectively. Immunogenicity evaluations for Stage I data (Visits 5 and 6) were conducted together with Stage II data.

Official Title
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A Bridging Study: Comparing Two Sci-B-Vac™ Batches in Healthy Adults

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Sci-B-Vac-Lot B
* Biological: Sci-B-Vac-Lot A
* Biological: Engerix-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18 to 45 years of age who were seronegative for HBsAg, anti-HBs, anti-Hepatitis B core antigen, HIV, and Hepatitis C Virus (HCV) Exclusion Criteria: Evidence of alcoholism or drug abuse, history of HIV, or HCV Blood transfusions within the three months prior to inclusion in the study Uncontrolled hypertension and other cardiovascular diseases Chronic/concurrent administration (>14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled and topical steroids were permitted History of anaphylaxis (including shock) or any significant allergy or atopy

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
Interventional Model Description: Single blind, three-arm, two-stage, randomized study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sci-B-Vac-SciGen<br>The 3-antigen HepB vaccine, Sci-B-Vac-SciGen (SciGen Israel Ltd., produced in a new production facility located in Rehovot, Israel) contains three recombinant proteins of hepatitis B virus (HBV) envelope: small S, medium pre-S2, and large pre-S1 surface antigens. Sci-B-Vac-SciGen was supplied in a final volume of 1.2 ml vials | Biological: Sci-B-Vac-Lot B<br>* Sci-B-Vac Lot B -10 μg of HBsAg, intramuscular injection of 10 μg/ml<br>* Other names: Bio-Hep-B;|
| 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 (hepatitis B vaccine (recombinant)) is indicated for active immunization against hepatitis B virus infection<br>|
| Experimental: Sci-B-Vac-BTG<br>The 3-antigen HepB vaccine, Sci-B-Vac-BTG (Bio-Technology General (BTG) Ltd., Rehovot, Israel.) contains three recombinant proteins of HBV viral envelope: small S, medium pre-S2, and large pre-S1 surface antigens. Sci-B-Vac-BTG was supplied in a final volume of 1.2 ml vials | Biological: Sci-B-Vac-Lot A<br>* Sci-B-Vac Lot A - 10 μg of HBsAg, intramuscular injection of 10 μg/ml<br>* Other names: Bio-Hep-B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination | Percentage of participants with an antibody response to hepatitis B surface antigens (anti-HBs), defined as an anti-HBs titer ≥10 IU/liter, one month after the third vaccination (Day 210) in the According-to-Protocol (ATP) population. | Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. | Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥10 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. | Days 180, 210, and 360 | 
| Anti-HBs Geometric Mean Concentration (GMC) | Geometric mean concentration (GMC) of anti-HBs antibody just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. | Days 180, 210, and 360 | 
| Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. | Percentage of participants with an anti-HBs antibody response, defined as an anti-HBs titer ≥100 IU/liter, just prior to the third vaccination (Day 180) and 1 month (Day 210) and 6 months (Day 360) after the third vaccination in the According-to-Protocol (ATP) population. | Days 180, 210 and 360 | 

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