Hepatitis B VaccinesPhase 3NCT03393754
Immunogenicity and Safety of Sci-B-Vac® to Engerix-B® in Adults
A Phase 3 study testing Hepatitis B Vaccination in people with Hepatitis B Vaccines, run by VBI Vaccines Inc. at 28 sites in 4 countries.
Trial summary
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in ≥ 45 years old. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B Vaccines
- What is being tested?
- Hepatitis B Vaccination
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,607 participants
- Where
- 28 sitesin 4 countries
- Study dates
- 13 Dec 2017to 8 Apr 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Any gender.
- Age ≥ 18 years
- In stable health as determined by a physical examination and laboratory tests values. Common chronic conditions such as, but not limited to, type 2 diabetes, high blood pressure, Chronic Obstructive Pulmonary Disease (COPD) and asthma will be accepted if the condition is well controlled, as determined by the investigator, and not meeting the exclusion criteria. For subjects > 65 years old, Frailty Index ≤3
- If female, either is not of childbearing potential or is of childbearing potential and must agree to use an adequate birth control method during the screening period and until the end of her participation in the study
- Able and willing to give consent.
Who cannot join
- Previous vaccination with any Hep B vaccine (licensed or experimental).
- Treatment by immunosuppressant within 30 days of enrollment including but not limited to corticosteroids at a dose that is higher than an oral or injected physiological dose, or a prednisolone-equivalent dose > 20 mg /day (Inhaled and topical steroids are allowed).
- Known history of immunological function impairment
- Pregnancy or breastfeeding
- Immunization with attenuated vaccines (e.g. MMR) within 4 weeks prior to enrollment
- Immunization with inactivated vaccines (e.g. influenza) within 2 weeks prior to enrolment
Show all 22Show fewer
- Has received blood products or immunoglobulin within 90 days of enrollment or is likely to require blood products during the study period
- Subject in another clinical trial with an investigational drug or a biologic within 30 days of enrollment
- Has received granulocyte-macrophage colony stimulating factor (G/GM-CSF) or erythropoietin (EPO) within 30 days of enrollment or likely to require GM-CSF or erythropoietin during the study period
- Any history of cancer requiring chemotherapy or radiation within 5 years of randomization or current disease.
- Any skin abnormality or tattoo that would limit post-vaccination injection site assessment
- History of allergic reactions or anaphylactic reaction to any vaccine component (Engerix-B® or Sci-B-Vac®)
- Unwilling, or unable in the opinion of the investigator, to comply with study requirements, including the use of an adequate birth control method
- Immediate family members of study center staff (parents, sibling, children)
- Current or past hepatitis B infection or prior vaccination as evidenced by HBV markers at screening
- Known hepatitis C infection or positive Hepatitis C serology at screening, unless treated and cured
- Known human immunodeficiency virus (HIV) infection or positive HIV serology at screening
- Renal impairment at screening
- Uncontrolled diabetes mellitus
- Uncontrolled hypertension
- Any laboratory test abnormality that would be considered of Grade 1 severity and is considered as clinically significant by the investigator. Grade 3 severity or above is exclusionary, regardless of clinical assessment.
- Diagnosis of advanced stage heart failure or Unstable Angina.
Trial locations and contacts
28 sites in 4 countries.
28 sites in 4 countries
United States10 sites
Anaheim Clinical Trials
Anaheim, California, 92801
Clinical Research Atlanta
Atlanta, Georgia, 30281
Accel Research Sites
Birmingham, Alabama, 35216
Advanced Clinical Research
Boise, Idaho, 83642
Rapid Medical Research
Cleveland, Ohio, 44122
Avail Clinical Research
DeLand, Florida, 32720
Clinical Research Center of Nevada
Las Vegas, Nevada, 89104
Suncoast Research Group
Miami, Florida, 33135
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Advanced Clinical Research
Salt Lake City, Utah, 84088
Finland10 sites
Espoo Vaccine Research Clinic
Espoo
Helsinki South Vaccine Research Clinic
Helsinki
Järvenpää Vaccine Research Clinic
Jarvenpaa
Kokkola Vaccine Research Clinic
Kokkola
Oulu Vaccine Research Clinic
Oulu
Pori Vaccine Research Clinic
Pori
Seinäjoki Vaccine Research Clinic
Seinäjoki
Tampere Vaccine Research Clinic
Tampere
University of Tampere
Tampere
Turku Vaccine Research Clinic
Turku
Canada7 sites
Medicore Research Inc
Greater Sudbury, Ontario, P3A 1W8
Canadian Center for Vaccinology
Halifax, Nova Scotia
McGill University Health Centre
Montreal, Quebec
Ottawa Hospital
Ottawa, Ontario
CHU de Québec Université Laval
Québec, Quebec
BC Children's Hospital Research Institute
Vancouver, British Columbia
University of Manitoba
Winnipeg, Manitoba
About this study
Official title: A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac® to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in ≥ 45 years old.
Read the detailed description
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 45 years old. Study subjects are randomized 1:1 to receive either a total of 3 injections of Sci-B-Vac® or 3 injections of Engerix-B® intra-muscularly (IM) on Days 0, 28, and 168.
- Conditions
- Hepatitis B Vaccines
- Being tested
- Hepatitis B Vaccination
- Keywords
- Hepatitis B Vaccines
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatitis B VaccinationBiological
Prophylactic Hepatitis B Vaccination
| Study group | Role | What they receive |
|---|---|---|
| Sci-B-Vac® Hepatitis B Vaccination | Experimental | Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. Receives: Biological: Hepatitis B Vaccination |
| Engerix-B® Hepatitis B Vaccination | Active comparator | Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. Receives: Biological: Hepatitis B Vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is non-inferior to a three-dose regimen of Engerix-B® in adults ≥18 years old; i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after the third vaccination, will be > - 5%.
Measured: Day 196
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > 5%.
Measured: Day 196
Secondary outcomes (1)
Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs)
Analysis of local and systemic solicited adverse events with an interval of onset of Day 1 to Day 7 after any vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.
Measured: Day of vaccine administration and six subsequent days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start13 Dec 2017
- Primary completion8 Apr 2019
- Study completion8 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B VaccinesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,607 participants (actual)
Sponsor and investigators
- Lead sponsor
- VBI Vaccines Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Francisco Diaz-Mitoma, MD, PhD, Study director, VBI Vaccines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03393754
- Sponsor's protocol ID
- Sci-B-Vac-001
- Other IDs
- 2017-001819-36, 2017
- Status last verified
- Jul 2020
- First submitted
- 23 Nov 2017
- Last updated
- 17 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Berthoud TK, Ahmed T, Nadia W, Petrov I, Yang L, Colledge D, Hammond R, Soare C, Ontsouka B, Plaskin D, Anderson DE, Diaz-Mitoma F. A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers. Vaccine. 2025 Jan 1;43(Pt 2):126513. doi: 10.1016/j.vaccine.2024.126513. Epub 2024 Nov 12.
PubMed 39536477Talbird SE, Anderson SA, Nossov M, Beattie N, Rak AT, Diaz-Mitoma F. Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States. Vaccine. 2023 May 26;41(23):3506-3517. doi: 10.1016/j.vaccine.2023.04.022. Epub 2023 May 3.
PubMed 37147201Vesikari T, Langley JM, Segall N, Ward BJ, Cooper C, Poliquin G, Smith B, Gantt S, McElhaney JE, Dionne M, van Damme P, Leroux-Roels I, Leroux-Roels G, Machluf N, Spaans JN, Yassin-Rajkumar B, Anderson DE, Popovic V, Diaz-Mitoma F; PROTECT Study Group. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021 Sep;21(9):1271-1281. doi: 10.1016/S1473-3099(20)30780-5. Epub 2021 May 11.
PubMed 33989539
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac® to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)
- ClinicalTrials.gov ID
- NCT03393754
- Acronym / sponsor ID
- Sci-B-Vac-001
- Conditions
- Hepatitis B Vaccines
- Keywords
- Hepatitis B Vaccines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,607 participants (actual)
- Lead sponsor
- VBI Vaccines Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 8 Apr 2019 (actual)
- Study completion
- 8 Apr 2019 (actual)
- First posted
- 8 Jan 2018 (actual)
- Results
- Posted 7 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in ≥ 45 years old.
Detailed description
This study is a double-blind randomized controlled trial designed to establish the non-inferiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 18 years old and the superiority of Sci-B-Vac® compared to Engerix-B® in adults ≥ 45 years old. Study subjects are randomized 1:1 to receive either a total of 3 injections of Sci-B-Vac® or 3 injections of Engerix-B® intra-muscularly (IM) on Days 0, 28, and 168.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sci-B-Vac® Hepatitis B Vaccination | Experimental | Biological: Hepatitis B VaccinationSci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. |
| Engerix-B® Hepatitis B Vaccination | Active comparator | Biological: Hepatitis B VaccinationEngerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Any gender.
- Age ≥ 18 years
- In stable health as determined by a physical examination and laboratory tests values. Common chronic conditions such as, but not limited to, type 2 diabetes, high blood pressure, Chronic Obstructive Pulmonary Disease (COPD) and asthma will be accepted if the condition is well controlled, as determined by the investigator, and not meeting the exclusion criteria. For subjects > 65 years old, Frailty Index ≤3
- If female, either is not of childbearing potential or is of childbearing potential and must agree to use an adequate birth control method during the screening period and until the end of her participation in the study
- Able and willing to give consent.
Key exclusion criteria (22 listed)
- Previous vaccination with any Hep B vaccine (licensed or experimental).
- Treatment by immunosuppressant within 30 days of enrollment including but not limited to corticosteroids at a dose that is higher than an oral or injected physiological dose, or a prednisolone-equivalent dose > 20 mg /day (Inhaled and topical steroids are allowed).
- Known history of immunological function impairment
- Pregnancy or breastfeeding
- Immunization with attenuated vaccines (e.g. MMR) within 4 weeks prior to enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hepatitis B VaccinationProphylactic Hepatitis B Vaccination | Biological | Engerix-B® Hepatitis B Vaccination, Sci-B-Vac® Hepatitis B Vaccination |
Primary outcome
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
Time frame: Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is non-inferior to a three-dose regimen of Engerix-B® in adults ≥18 years old; i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after the third vaccination, will be > - 5%.
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 45 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196
Time frame: Day 196
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > 5%.
1 secondary outcome
Percentage of Subject-reporting Solicited Local and Systemic Adverse Events (AEs)
Time frame: Day of vaccine administration and six subsequent days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39536477Berthoud TK, Ahmed T, Nadia W, Petrov I, Yang L, Colledge D, Hammond R, Soare C, Ontsouka B, Plaskin D, Anderson DE, Diaz-Mitoma F. A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers. Vaccine. 2025 Jan 1;43(Pt 2):126513. doi: 10.1016/j.vaccine.2024.126513. Epub 2024 Nov 12.
- Derived from this study: PubMed 37147201Talbird SE, Anderson SA, Nossov M, Beattie N, Rak AT, Diaz-Mitoma F. Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States. Vaccine. 2023 May 26;41(23):3506-3517. doi: 10.1016/j.vaccine.2023.04.022. Epub 2023 May 3.
- Derived from this study: PubMed 33989539Vesikari T, Langley JM, Segall N, Ward BJ, Cooper C, Poliquin G, Smith B, Gantt S, McElhaney JE, Dionne M, van Damme P, Leroux-Roels I, Leroux-Roels G, Machluf N, Spaans JN, Yassin-Rajkumar B, Anderson DE, Popovic V, Diaz-Mitoma F; PROTECT Study Group. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021 Sep;21(9):1271-1281. doi: 10.1016/S1473-3099(20)30780-5. Epub 2021 May 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Diaz-Mitoma, MD, PhD study director
VBI Vaccines
28 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hepatitis B Vaccination in people with Hepatitis B Vaccines, run by VBI Vaccines Inc. at 28 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Finland, Canada, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seroprotection Rate (SPR) Defined as Percentage of Adults ≥ 18 Years Old Achieving Anti-HBs Levels of ≥10 mIU/mL in Serum at Study Day 196 (time frame: Day 196). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03393754, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2020.