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

• Sponsor: VBI Vaccines Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04531098
• Collaborator: (none)
• Enrollment: 402
• Location: 1
• Arms: 3
• Actual Duration (Months): 34
• Patients Per Site Per Month: 11.8

Study Details

Study Description

Brief Summary

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

1. 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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Biological: Sci-B-Vac-Lot B; Biological: Sci-B-Vac-Lot A; Biological: Engerix-B	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 402 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single blind, three-arm, two-stage, randomized studySingle blind, three-arm, two-stage, randomized study
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Bridging Study: Comparing Two Sci-B-Vac™ Batches in Healthy Adults
• Actual Study Start Date: Mar 2, 2006
• Actual Primary Completion Date: Dec 31, 2008
• Actual Study Completion Date: Dec 31, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sci-B-Vac-SciGen 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; Sci-B-Vac Lot B -10 μg of HBsAg, intramuscular injection of 10 μg/ml; Other Names: Sci-B-Vac 3-antigen HepB Vaccine Bio-Hep-B
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 (hepatitis B vaccine (recombinant)) is indicated for active immunization against hepatitis B virus infection
Experimental: Sci-B-Vac-BTG 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; Sci-B-Vac Lot A - 10 μg of HBsAg, intramuscular injection of 10 μg/ml; Other Names: Sci-B-Vac 3-antigen HepB Vaccine Bio-Hep-B

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination [Day 210]

   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.

Secondary Outcome Measures

1. Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360. [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.

2. Anti-HBs Geometric Mean Concentration (GMC) [Days 180, 210, and 360]

   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.

3. Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360. [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute of Hygiene and Epidemiology (NIHE)	Hanoi		Vietnam

Sponsors and Collaborators

• VBI Vaccines Inc.

Investigators

• Principal Investigator: Do G Canh, MD, National Institute of Hygiene and Epidemiology (NIHE), Hanoi, Vietnam

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VBI Vaccines Inc.
• ClinicalTrials.gov Identifier: NCT04531098
• Other Study ID Numbers: SG-005-05
• First Posted: Aug 28, 2020
• Last Update Posted: Jul 26, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by VBI Vaccines Inc.: Sci-B-Vac; Prophylactic vaccine; Hepatitis B vaccines; Phase 3; pre-S1; pre-S2; Surface antigen; 3-antigen
• Additional relevant MeSH terms: Hepatitis B; Hepatitis; Vaccines

Study Results

Participant Flow

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
Period Title: Stage I
STARTED	0	67	134
COMPLETED	0	62	116
NOT COMPLETED	0	5	18
Period Title: Stage I
STARTED	134	67	0
COMPLETED	121	57	0
NOT COMPLETED	13	10	0

Baseline Characteristics

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A	Total
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The mono-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	Total of all reporting groups
Overall Participants	131	133	134	398
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	131 100%	133 100%	134 100%	398 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.58 (1.577)	20.48 (1.655)	20.79 (2.392)	20.62 (1.913)
Sex: Female, Male (Count of Participants)
Female	94 71.8%	89 66.9%	89 66.4%	272 68.3%
Male	37 28.2%	44 33.1%	45 33.6%	126 31.7%
Region of Enrollment (Count of Participants)
Vietnam	131 100%	133 100%	134 100%	398 100%
Ethnic Group (Count of Participants)
White/Caucasian	0 0%	0 0%	0 0%	0 0%
Black	0 0%	0 0%	0 0%	0 0%
Asian	131 100%	133 100%	134 100%	398 100%
Other	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	50.2 (5.9)	50.2 (7.3)	51.8 (6.0)	50.8 (6.5)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	20.1 (1.5)	20.0 (2.2)	20.9 (1.9)	20.3 (1.9)
Smoking status (Count of Participants)
Smoker	3 2.3%	6 4.5%	1 0.7%	10 2.5%
Non-smoker	128 97.7%	127 95.5%	133 99.3%	388 97.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an Antibody Response (≥10 IU/Liter) to Hepatitis B Surface Antigens One Month After the Third Vaccination
Description	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.
Time Frame	Day 210

Outcome Measure Data

Analysis Population Description

The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
Measure Participants	120	117	112
Count of Participants [Participants]	120 91.6%	115 86.5%	109 81.3%

2. Secondary Outcome

Title	Percentage of Participants With an Anti-HBs Antibody Titer ≥10 IU/Liter at Days 180, 210 and 360.
Description	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.
Time Frame	Days 180, 210, and 360

Outcome Measure Data

Analysis Population Description

The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
Measure Participants	120	117	112
Day 180	118 90.1%	95 71.4%	102 76.1%
Day 210	120 91.6%	115 86.5%	109 81.3%
Day 360	115 87.8%	110 82.7%	101 75.4%

3. Secondary Outcome

Title	Anti-HBs Geometric Mean Concentration (GMC)
Description	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.
Time Frame	Days 180, 210, and 360

Outcome Measure Data

Analysis Population Description

The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
Measure Participants	120	117	112
Day 180	328.64	44.42	147.30
Day 210	12,158.94	4,124.24	3,587.30
Day 360	3188.68	991.07	1239.82

4. Secondary Outcome

Title	Percentage of Participants With an Anti-HBs Antibody Titer ≥100 IU/Liter at Days 180, 210 and 360.
Description	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.
Time Frame	Days 180, 210 and 360

Outcome Measure Data

Analysis Population Description

The according-to-protocol (ATP) population included all participants who received the three vaccinations, the third vaccination measurement of anti-HBs titers, and had no major protocol violations.

Arm/Group Title	Sci-B-Vac-Lot B	Engerix-B	Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml	The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.	The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
Measure Participants	120	117	112
Day 180	99 75.6%	40 30.1%	68 50.7%
Day 210	118 90.1%	113 85%	106 79.1%
Day 360	113 86.3%	100 75.2%	94 70.1%

Adverse Events

Time Frame	Subjects were assessed for safety at baseline, during treatment (Day 30, Day 180) and during follow up (Day 210, Day 310).
Adverse Event Reporting Description	Adverse events (AEs) were reported throughout the study and were rated by the investigator for severity and causality. All serious AEs (SAEs) and fatalities were reported immediately. Local and systemic solicited adverse reactions were recorded after each vaccination on participant diary cards. AEs were rated by the investigators for severity and causality. All fatalities and SAE were reported to SciGen Ltd and Pharmacovigilance of Quintiles Asia Pacific, Singapore.
Arm/Group Title	Sci-B-Vac-Lot B		Engerix-B		Sci-B-Vac-Lot A
Arm/Group Description	The 3-antigen HepB vaccine, Sci-B-Vac-Lot B (SciGen Israel Ltd., New Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml		The single-antigenic HepB vaccine, Engerix-B (GSK), contains the small S recombinant protein indicated for active immunization against hepatitis B virus infection. Engerix-B was supplied in 1.0 ml vials.		The 3-antigen HepB vaccine, Sci-B-Vac-Lot A (Bio-Technology General (BTG) Ltd., Old Facility) contains10 μg of HBsAg/preS1/S2 injected intramuscularly at 10 μg/ml
All Cause Mortality
	Sci-B-Vac-Lot B		Engerix-B		Sci-B-Vac-Lot A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/131 (0%)		0/133 (0%)		0/134 (0%)
Serious Adverse Events
	Sci-B-Vac-Lot B		Engerix-B		Sci-B-Vac-Lot A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/131 (0.8%)		4/133 (3%)		3/134 (2.2%)
Blood and lymphatic system disorders
anemia	0/131 (0%)	0	1/133 (0.8%)	1	0/134 (0%)	0
General disorders
pyrexia	0/131 (0%)	0	1/133 (0.8%)	1	0/134 (0%)	0
Infections and infestations
hepatitis B	0/131 (0%)	0	1/133 (0.8%)	1	0/134 (0%)	0
gastritis	0/131 (0%)	0	1/133 (0.8%)	1	0/134 (0%)	0
Injury, poisoning and procedural complications
ilium fracture	0/131 (0%)	0	0/133 (0%)	0	1/134 (0.7%)	1
Musculoskeletal and connective tissue disorders
osteitis	0/131 (0%)	0	0/133 (0%)	0	1/134 (0.7%)	1
Psychiatric disorders
schizophrenia	0/131 (0%)	0	0/133 (0%)	0	1/134 (0.7%)	1
Vascular disorders
Circulatory collapse	1/131 (0.8%)	1	0/133 (0%)	0	0/134 (0%)	0
Other (Not Including Serious) Adverse Events
	Sci-B-Vac-Lot B		Engerix-B		Sci-B-Vac-Lot A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/131 (48.1%)		26/133 (19.5%)		83/134 (61.9%)
Cardiac disorders
Dizziness	1/131 (0.8%)		1/133 (0.8%)		0/134 (0%)
General disorders
Injection site pain	57/131 (43.5%)		19/133 (14.3%)		79/134 (59%)
Fatigue	10/131 (7.6%)		6/133 (4.5%)		14/134 (10.4%)
Malaise	3/131 (2.3%)		4/133 (3%)		12/134 (9%)
Injection site pruritus	4/131 (3.1%)		3/133 (2.3%)		7/134 (5.2%)
Pyrexia	1/131 (0.8%)		0/133 (0%)		2/134 (1.5%)
Injection site swelling	1/131 (0.8%)		0/133 (0%)		0/134 (0%)
Feeling hot	0/131 (0%)		1/133 (0.8%)		0/134 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	16/131 (12.2%)		3/133 (2.3%)		18/134 (13.4%)
Arthralgia	2/131 (1.5%)		0/133 (0%)		4/134 (3%)
Skin and subcutaneous tissue disorders
Pruritus	1/131 (0.8%)		3/133 (2.3%)		3/134 (2.2%)
Vascular disorders
Circulatory collapse	1/131 (0.8%)		0/133 (0%)		0/134 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.