Hepatitis BPhase 4NCT04179786
A Study to Qualify an In-house Reference Standard Batch of Sci-B-Vac™
A Phase 4 study testing Sci-B-Vac™ in people with Hepatitis B, run by VBI Vaccines Inc..
Trial summary
Each Sci-B-Vac™ lot to be released to the market is tested in comparison to a reference batch,which has to be tested in a human clinical trial. This study was conducted by SciVac Ltd. Read more about this study
- Who is it for?
- Ages 20 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Sci-B-Vac™
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2015to 25 Apr 2017
- Phase
- Phase 4
- 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 20 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males and females 20 - 40 years of age.
- Subjects who provided written informed consent to participate in the study.
- Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
- No clinically-significant abnormalities in hematology, blood chemistry, or urinalysis lab tests at Screening.
- Women of child-bearing potential had to practice an acceptable method of birth control or practice abstinence during the study period or be surgically sterilized, from Screening visit throughout the vaccination phase and for 28 days after the last injection and agree to undergo repeated pregnancy tests.
- Subjects had to be able to understand the requirements of the study and willing to comply with the requirements of the study.
Who cannot join
- Known history of significant medical disorder, which in the investigator's judgment contraindicates administration of the vaccine or may interfere with the subject's compliance or the interpretation of study assessment parameters.
- Any clinically-significant abnormality upon physical examination or in the clinical laboratory tests at Screening visit.
- Treatment with immune suppressive agents.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- History of Hepatitis B virus (HBV) infection or confirmed exposure to HBV
- Previous vaccination against Hepatitis B.
Show all 17Show fewer
- Positive for HBsAg, anti-HBs antibodies, anti-HBc antibodies, anti-HCV (hepatitis C virus) antibodies or anti- HIV antibodies.
- Drug abuse
- Known hypersensitivity or allergy to any component of the study vaccine.
- Body mass index (BMI) < 18.5 or ≥ 30 kg/m2.
- Known concomitant disease or any other medical condition that is considered by the investigator likely to interfere with the subject's compliance or the interpretation of study assessments.
- Any acute illness (e.g. acute infection) within 48 hours prior to the first study drug administration that is considered of significance by the Principal Investigator.
- Female subjects: pregnant, lactating or planning a pregnancy.
- Any confirmed or suspected immunosuppressive or immunodeficient condition.
- Receipt of blood or immunoglobulin transfusion six months prior to the first vaccine dose and during the course of the trial.
- Unwilling or unable (in the judgment of the investigator) to comply with all the requirements of the protocol.
- Participate in another clinical trial within 3 months prior to first vaccination (calculated from the previous study's last dosing date).
About this study
Official title: An Open-label, Single Arm, Single Center Clinical Study In Healthy Subjects to Qualify an In-house Reference Standard Batch of Sci-B-Vac™
Each Sci-B-Vac™ lot to be released to the market is tested in comparison to a reference batch,which has to be tested in a human clinical trial. This study was conducted by SciVac Ltd. to to evaluate the immunogenicity and explore the immune kinetics of Sci-B-Vac™ in support of its qualification as new reference standard which according to the European Pharmacopeia (Ph.Eur. 1056) should elicit ≥ 95% seroprotection rate (SPR) of Hepatitis B surface (HBs) antibody concentrations ≥ 10 milli-International Units (mIU) per ml in young, healthy adult subjects.
Read the detailed description
This study was a post-marketing, open-label, single arm study in healthy volunteers who had never been vaccinated with any hepatitis B vaccine and were seronegative to HBsAg, Hepatitis B core (HBc) and HBs antibodies. This study consisted of three periods: screening period (up to 1 month prior to first vaccination), treatment (Day 1 to month 6), and post-vaccination follow-up period (months 6 -12). Immunogenicity endpoints were examined one month after the first injection and at every month until month 6, then at months 7, 9 and 12. The primary safety endpoint was the frequency, severity, and duration of adverse events, including clinically-significant laboratory abnormalities after administration of Sci-B-Vac™.
Statistical Methods: A total of 92 subjects were recruited into the study. Subjects who fully complied with the study protocol, had no inclusion/exclusion criteria violation and who early terminated the study but reached the primary endpoint prior to withdrawal (modified intention-to-treat (mITT) population) were included in the final population for statistical analysis. mITT population was defined as the subset of the ITT set, which consisted of all enrolled subjects who were vaccinated at least once with Sci-B-Vac™ and had at least one post-vaccination follow-up visit, fully complied with the protocol and had no violation of the inclusion/exclusion criteria. Eligible subjects were followed for a total duration of 12 months.
Significance Level: The overall significance level for this study was 5% using two-tailed tests. Sample size determination was performed under the following assumptions:
The primary endpoint for the study was the SPR, defined as the proportion of subjects with HBs antibody titer ≥10 mIU/ml by month 7 (i.e. one month after the third immunization with Sci-B-Vac™). Subjects terminated early from the study for any reason at any time and who met the primary endpoint were included.
In compliance with the European Pharmacopeia, the SPR threshold was set at ≥ 95%. Based on a 9% margin of non-inferiority, the study was considered successful if the lower bound of the 95.0% exact confidence interval (CI) was 86.0% or more (lower non-inferiority limit) by month 7.
The secondary objective of the study was to explore kinetics of immune response induced by Sci-B-Vac™ based on serial immunogenicity measurements.
Demographic and baseline data as well as disease prognostic factors, medical history and prior medications were summarized for the mITT population,For continuous variables, descriptive statistics (number [n], mean, standard deviation (SD), standard error, median, minimum, and maximum) were provided. For categorical variables, subject counts and percentages were provided.
- Conditions
- Hepatitis B
- Being tested
- Sci-B-Vac™
- Keywords
- SciB018, Prophylactic vaccine, Sci-B-Vac™, HepB vaccines, Phase 4, pre-S1, pre-S2, Surface antigen
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sci-B-Vac™Biological
Sci-B-Vac™ is a recombinant Hepatitis B vaccine, produced by SciVac Israel Ltd under good manufacturing practices (GMP). It contains the 3 surface antigens of the Hepatitis B virus: HBs, pre-S1 and pre-S2. Each 1 ml dose contains sterile 10 μg Hepatitis B virus surface antigens. It is formulated for intramuscular injection supplied in single use vials containing 1ml suspension.
| Study group | Role | What they receive |
|---|---|---|
| Sci-B-Vac™ | Other | Single arm study in healthy volunteers who had never been vaccinated with any hepatitis B vaccine and who were seronegative for antibodies to HBsAg, HBc and HBs at baseline. Receives: Biological: Sci-B-Vac™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroprotection Rate Achieved One Month After the Third Immunization With Sci-B-Vac™.
SPR (% of subjects ≥ 10 mIU/mL) one month after immunization with Sci-B-Vac™ at months 0, 1 and 6 was calculated by measuring the HBs antibody titers using Cobas™ e601 anti-HBs assay. Subjects who received at least one Sci-B-Vac™ dose and early terminated from the study for any reason at any time while having HBs antibody concentrations ≥ 10 mIU/ml were considered among those who met the endpoint.
Measured: Month 7 (i.e. one month after the third immunization with Sci-B-Vac™)
Secondary outcomes (3)
Seroprotection Rates Achieved Monthly During Treatment and Then at Month 7, 9 and 12 During Follow-up
The endpoint for the study was the SPR, defined as the percentage of subjects with HBs antibody titer ≥10 mIU/ml. The Cobas™ e601 anti-HBs assay was used to assess the HBs antibody titer.
Measured: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Percentage of Subjects With HBs Antibody Titer ≥100 mIU/ml at Each Timepoint
The outcome was the proportion of subjects with HBs antibody titer ≥100 mIU/ml. The Cobas™ e601 anti-HBs assay was used to assess the HBs antibody titer.
Measured: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Geometric Mean Concentration (GMC) as Determined by HBs Antibody Titers
The Cobas™ e601 anti-HBs assay was used to assess the HBs antibody titer.
Measured: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2019
- Study start1 Nov 2015
- Primary completion7 Feb 2017
- Study completion25 Apr 2017
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 (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study was an open-label, single arm study. No control groups were deemed necessary since this was a phase IV trial for which the goal, set according to the European Pharmacopeia 1056, was to achieve 95% SPR after the third vaccination.
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- VBI Vaccines Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jacob Atsmon, MD, Study director, TASMC Clinical Research Center (CRC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04179786
- Sponsor's protocol ID
- SciB018
- Status last verified
- Mar 2022
- First submitted
- 7 Oct 2019
- Last updated
- 24 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Atsmon J, Machluf N, Yayon-Gur V, Sabbah C, Spaans JN, Yassin-Rajkumar B, Anderson DE, Popovic V, Diaz-Mitoma F. Rapid and high seroprotection rates achieved with a tri-antigenic Hepatitis B vaccine in healthy young adults: Results from a Phase IV study. Vaccine. 2021 Feb 22;39(8):1328-1332. doi: 10.1016/j.vaccine.2020.12.050. Epub 2021 Jan 13.
PubMed 33451780
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm, Single Center Clinical Study In Healthy Subjects to Qualify an In-house Reference Standard Batch of Sci-B-Vac™
- ClinicalTrials.gov ID
- NCT04179786
- Acronym / sponsor ID
- SciB018
- Conditions
- Hepatitis B
- Keywords
- SciB018, Prophylactic vaccine, Sci-B-Vac™, HepB vaccines, Phase 4, pre-S1, pre-S2, Surface antigen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- VBI Vaccines Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 7 Feb 2017 (actual)
- Study completion
- 25 Apr 2017 (actual)
- First posted
- 27 Nov 2019 (actual)
- Results
- Posted 24 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Each Sci-B-Vac™ lot to be released to the market is tested in comparison to a reference batch,which has to be tested in a human clinical trial. This study was conducted by SciVac Ltd. to to evaluate the immunogenicity and explore the immune kinetics of Sci-B-Vac™ in support of its qualification as new reference standard which according to the European Pharmacopeia (Ph.Eur. 1056) should elicit ≥ 95% seroprotection rate (SPR) of Hepatitis B surface (HBs) antibody concentrations ≥ 10 milli-International Units (mIU) per ml in young, healthy adult subjects.
Detailed description
This study was a post-marketing, open-label, single arm study in healthy volunteers who had never been vaccinated with any hepatitis B vaccine and were seronegative to HBsAg, Hepatitis B core (HBc) and HBs antibodies. This study consisted of three periods: screening period (up to 1 month prior to first vaccination), treatment (Day 1 to month 6), and post-vaccination follow-up period (months 6 -12). Immunogenicity endpoints were examined one month after the first injection and at every month until month 6, then at months 7, 9 and 12. The primary safety endpoint was the frequency, severity, and duration of adverse events, including clinically-significant laboratory abnormalities after administration of Sci-B-Vac™.
Statistical Methods: A total of 92 subjects were recruited into the study. Subjects who fully complied with the study protocol, had no inclusion/exclusion criteria violation and who early terminated the study but reached the primary endpoint prior to withdrawal (modified intention-to-treat (mITT) population) were included in the final population for statistical analysis. mITT population was defined as the subset of the ITT set, which consisted of all enrolled subjects who were vaccinated at least once with Sci-B-Vac™ and had at least one post-vaccination follow-up visit, fully complied with the protocol and had no violation of the inclusion/exclusion criteria. Eligible subjects were followed for a total duration of 12 months.
Significance Level: The overall significance level for this study was 5% using two-tailed tests. Sample size determination was performed under the following assumptions:
The primary endpoint for the study was the SPR, defined as the proportion of subjects with HBs antibody titer ≥10 mIU/ml by month 7 (i.e. one month after the third immunization with Sci-B-Vac™). Subjects terminated early from the study for any reason at any time and who met the primary endpoint were included.
In compliance with the European Pharmacopeia, the SPR threshold was set at ≥ 95%. Based on a 9% margin of non-inferiority, the study was considered successful if the lower bound of the 95.0% exact confidence interval (CI) was 86.0% or more (lower non-inferiority limit) by month 7.
The secondary objective of the study was to explore kinetics of immune response induced by Sci-B-Vac™ based on serial immunogenicity measurements.
Demographic and baseline data as well as disease prognostic factors, medical history and prior medications were summarized for the mITT population,For continuous variables, descriptive statistics (number [n], mean, standard deviation (SD), standard error, median, minimum, and maximum) were provided. For categorical variables, subject counts and percentages were provided.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study was an open-label, single arm study. No control groups were deemed necessary since this was a phase IV trial for which the goal, set according to the European Pharmacopeia 1056, was to achieve 95% SPR after the third vaccination.
| Arm | Type | Receives |
|---|---|---|
| Sci-B-Vac™ | Other | Biological: Sci-B-Vac™Single arm study in healthy volunteers who had never been vaccinated with any hepatitis B vaccine and who were seronegative for antibodies to HBsAg, HBc and HBs at baseline. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy males and females 20 - 40 years of age.
- Subjects who provided written informed consent to participate in the study.
- Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
- No clinically-significant abnormalities in hematology, blood chemistry, or urinalysis lab tests at Screening.
- Women of child-bearing potential had to practice an acceptable method of birth control or practice abstinence during the study period or be surgically sterilized, from Screening visit throughout the vaccination phase and for 28 days after the last injection and agree to undergo repeated pregnancy tests.
Key exclusion criteria (17 listed)
- Known history of significant medical disorder, which in the investigator's judgment contraindicates administration of the vaccine or may interfere with the subject's compliance or the interpretation of study assessment parameters.
- Any clinically-significant abnormality upon physical examination or in the clinical laboratory tests at Screening visit.
- Treatment with immune suppressive agents.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- History of Hepatitis B virus (HBV) infection or confirmed exposure to HBV
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 |
|---|---|---|
| Sci-B-Vac™Sci-B-Vac™ is a recombinant Hepatitis B vaccine, produced by SciVac Israel Ltd under good manufacturing practices (GMP). It contains the 3 surface antigens of the Hepatitis B virus: HBs, pre-S1 and pre-S2. Each 1 ml dose contains sterile 10 μg Hepatitis B virus surface antigens. It is formulated for intramuscular injection supplied in single use vials containing 1ml suspension. | Biological | Sci-B-Vac™ |
Primary outcome
Seroprotection Rate Achieved One Month After the Third Immunization With Sci-B-Vac™.
Time frame: Month 7 (i.e. one month after the third immunization with Sci-B-Vac™)
SPR (% of subjects ≥ 10 mIU/mL) one month after immunization with Sci-B-Vac™ at months 0, 1 and 6 was calculated by measuring the HBs antibody titers using Cobas™ e601 anti-HBs assay. Subjects who received at least one Sci-B-Vac™ dose and early terminated from the study for any reason at any time while having HBs antibody concentrations ≥ 10 mIU/ml were considered among those who met the endpoint.
3 secondary outcomes
Seroprotection Rates Achieved Monthly During Treatment and Then at Month 7, 9 and 12 During Follow-up
Time frame: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Percentage of Subjects With HBs Antibody Titer ≥100 mIU/ml at Each Timepoint
Time frame: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Geometric Mean Concentration (GMC) as Determined by HBs Antibody Titers
Time frame: At one month after the first injection, and then at every month until month 7 inclusive and at months 9 and 12.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33451780Atsmon J, Machluf N, Yayon-Gur V, Sabbah C, Spaans JN, Yassin-Rajkumar B, Anderson DE, Popovic V, Diaz-Mitoma F. Rapid and high seroprotection rates achieved with a tri-antigenic Hepatitis B vaccine in healthy young adults: Results from a Phase IV study. Vaccine. 2021 Feb 22;39(8):1328-1332. doi: 10.1016/j.vaccine.2020.12.050. Epub 2021 Jan 13.
- Individual participant dataSharing planned: No
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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.
Jacob Atsmon, MD study director
TASMC Clinical Research Center (CRC)
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sci-B-Vac™ in people with Hepatitis B, run by VBI Vaccines Inc..
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 6 inclusion and 17 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 24 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 24 Jun 2022). 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 Achieved One Month After the Third Immunization With Sci-B-Vac™. (time frame: Month 7 (i.e. one month after the third immunization with Sci-B-Vac™)). 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 NCT04179786, which also lists 1 linked publication.
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 24 Jun 2022.