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Hepatitis BPhase 1NCT02540538

Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders

A Phase 1 study testing HBVaxPro and HBAI20 in people with Hepatitis B, run by Maastricht University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether the HBAI20 vaccine is safe and more immunogenic than the HBVaxPro-10µg in people who have never been vaccinated with a hepatitis B vaccine and in people who have been vaccinated 6 times with hepatitis B vaccine but do not have a protective anti hepatitis B antibody… Read more about this study

Who is it for?
Ages 18 to 59 yearsHealthy volunteers can take part
Conditions the study is for
Hepatitis B
What is being tested?
HBVaxPro and HBAI20
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteNetherlands
Study dates
Sep 2015to Jul 2016
Phase
Phase 1
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 to 59 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • In good health as determined by the outcome of medical history, physical examination screening/baseline labs and clinical judgment of the clinical investigator
  • Age 18 to 59 years, inclusive at the time of enrolment
  • Willing and able to adhere to the study regimen
  • Having a signed informed consent form
  • Non-responders:
  • Documented non-responders: Subjects with documented two cycles of Hepatitis B vaccination (total of 6 vaccinations) and titer analysis that show that they have not developed the Hepatitis B antibody titer recommended after standard vaccination: anti-HBsAg antibody titer higher to 10mIU/ml.

Who cannot join

  • Any infectious disease at the time of screening and/or enrolment
  • Positive HIV, Hepatitis B virus or Hepatitis C virus serology
  • Positive anti-IL-2 antibody titer
  • Known or suspected immune deficiency
  • Known or suspected disease that influences the immune system including chronic allergies that require frequent anti-allergy medication, cancer and transplantation recipients
  • Known or suspected allergy to any of the vaccine components.
Show all 24Show fewer
  • Dialysis patient
  • History of unusual or severe reactions to any previous vaccination
  • History of any neurologic disorder, including epilepsy and autism
  • Use of medication that influences the immune system (immune suppressive treatment)
  • Any vaccination within 3 months before screening
  • Blood donation within 1 month before screening
  • Administration of plasma (incl. immunoglobulins) or blood products within 12 months before screening
  • Participation in another clinical trial within 3 months before screening
  • Abnormal pre-treatment laboratory parameters which are clinically relevant according to the investigator
  • Bleeding disorders, or use of medication for bleeding disorders, and use of anti-coagulants
  • Female subjects planning to become pregnant or breastfeeding babies until visit 7
  • Females: positive urine pregnancy test. Urine test positive at screening date or positive urine pregnancy test on the day of vaccination
  • Excessive alcohol or controlled drug use - More than 2 alcohol measures per day (one alcohol measure is a beer (250ml) or one glass of wine (125ml) or one strong measure (35ml) or one port/sherry (75ml)). Regular use of controlled drugs
  • Exclusion criterion for Hepatitis B naïve subjects (groups 1 and 2):
  • Previous vaccination with Hepatitis B vaccine
  • Any Hepatitis B vaccination in the last 6 months
  • Temporary exclusion criterion for vaccination
  • Ear temperature > 38.4°C will lead to postponement of participation and vaccination. Screening may continue when the temperature has normalized.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Maastricht UMC

    Maastricht, 6202 AZ

Other trials in Netherlands

About this study

The purpose of this study is to determine whether the HBAI20 vaccine is safe and more immunogenic than the HBVaxPro-10µg in people who have never been vaccinated with a hepatitis B vaccine and in people who have been vaccinated 6 times with hepatitis B vaccine but do not have a protective anti hepatitis B antibody titer.

Read the detailed description

Rationale: Worldwide, people are suffering from the consequences of Hepatitis B (HB) virus infection. Currently available vaccines are protective in most of the vaccinees, however, a small part of the population does not respond to these vaccines (non-responders). A new adjuvant (AI20) has been developed by CyTuVax to improve the standard Hepatitis B vaccine for the protection of non-responders. The AI20 adjuvant consists of depot-attached rhuIL-2 (aggregated Interleukin-2 molecules attached to alum), facilitating the slow release of highly concentrated IL-2 nano aggregates. As shown in preclinical experiments, vaccination of mice, rats, and rabbits with the new HBAI20 vaccine results in higher and earlier immune responses to Hepatitis B surface antigen (HBsAg) compared to vaccination with one of the standard Hepatitis B vaccines. This clinical study will be done in order to assess the safety of the AI20 adjuvant and test if the AI20 adjuvanted Hepatitis B vaccine induces protective antibody titers in the vaccinated non-responders.

Objective: In the current study we investigate the safety of the HBAI20 vaccine. Furthermore, the efficacy of the HBAI20 vaccine in non-responders is investigated.

Study design: Partly double blinded randomized controlled intervention phase I study, partly open-label phase I study.

Study population: Healthy volunteers (n=24) and registered non-responders (n=12), 18-59 years old, males and females.

Intervention: The study will include 3 groups. HB vaccine naïve healthy subjects are randomized into group 1 and 2 and registered non-responders are included in group 3.

"Group 1" subjects receive the standard HB vaccine (HBVaxPro-10µg), "Group 2" and "Group 3" subjects receive the HBAI20 vaccine. 2 subjects from "Group 3" will constitute "Group 3 pilot" and will start the study 7 days before the start of the remaining "Group 3" subjects.

All study subjects in groups 2 and 3 will receive two vaccinations with the assigned investigational medical product (IMP) at 0 and 1 month and one regular booster vaccination with the standard HB vaccine HBVaxPro-10µg 6 months after the first dose according to the recommended vaccination schedule for HBVaxPro-10µg.

Main study parameters/endpoints: The primary study parameter is the number and intensity of local and systemic adverse reactions (redness, swelling, impaired movement). The secondary study parameter is the HBAI20 vaccine immunogenicity as calculated by the median titer, geometric mean titer, geometric mean titer increase, proportion of subjects with a virus specific antibody titer measure by the COBAS system of ≥ 10 mIU/ml, and seroconversion rate. Seroconversion is defined as a four-fold increase in titer or a conversion from seronegative to an anti-HBsAg antibody titer of more than 10 mIU/ml after vaccinations.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Study subjects will be vaccinated 3 times at 0, 1 and 6 months from the beginning of the study and invited to the hospital for 8 visits. The risks associated with participation in this study are considered to be low and comparable with standard vaccines. Physical discomfort after vaccine administration can occur at the injection site (redness, swelling, etc.) and systemically (fever, fatigue, headache). Effects are expected to occur for a short period of time (within the first 4 days after the first and second injection). In addition subjects may experience adverse reactions to the cytokine component of the adjuvant. Because of the very low dose of the cytokine component of the adjuvant, which will be gradually released, the risks are expected to be low. The potential risks of venepuncture for blood sampling are mild pain and haematoma, and are considered low.

The naïve subjects participating in this study will benefit from participating by receiving immunization against Hepatitis B. Subjects in the non-responder group may benefit when they become responders due to the effect of the HBAI20 vaccine.

Conditions
Hepatitis B
Being tested
HBVaxPro, HBAI20
Keywords
Adjuvants, immunologic, Interleukin-2, Hepatitis B vaccines, Non-responders
Medical subject headings
Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HBVaxProBiological

    3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.

  • HBAI20Biological

    2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.

Study groups in NCT02540538
Study groupRoleWhat they receive
HB vaccine naive - HBVaxProActive comparatorSubjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
Receives: Biological: HBVaxPro
HB vaccine naive - HBAI20ExperimentalSubjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
Receives: Biological: HBAI20
Non-responders - HBAI20ExperimentalSubjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
Receives: Biological: HBAI20

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Subjects With Local and/or General Adverse Events Irrespective of Severity

    Subjects will be given a diary for 4 days after the first and second vaccination.

    Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4).

    Record medication taken during the study (up to 7 months after the first vaccination).

    Measured: Up to 7 months after first vaccination.

  2. Subjects With Local and/or General SEVERE Adverse Events

    Subjects will be given a diary for 4 days after the first and second vaccination.

    Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4).

    Record medication taken during the study (up to 7 months after the first vaccination).

    The laboratory parameters analysed at day 10, 30, 40, 60, 180, and 210 are:

    Hematology: Hematocrit, Hemoglobin, RBC count, WBC count, Platelet count, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes. Biochemistry: Creatinine, Albumin, Alkaline Phosphatase, Total Bilirubin, ALT (GPT), AST (GOT), Gamma-Gt, C-Reactive Protein, and TSH/FT4.

    Urinalysis (day 10, 40, and 210): Clarity, Color, Specific gravity, Leukocytes, Nitrite, pH, Erythrocytes, Albumin, and Glucose.

    Measured: Up to 7 months after first vaccination

Secondary outcomes (1)
  1. Number of Participants With Seroprotection

    Seroprotection at visit number 7, one month after the third vaccination. Anti-HBs antibodies were assayed from serum using a routine chemiluminescence assay (Anti-HBs, Cobas 8000, Roche, Germany). Titres >10 mIU/mL were considered to be seroprotective.

    Measured: Day 0, 10, 30, 40, 60, 180, and 210

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Sep 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionJul 2016
  4. Study completionJul 2016

Resources

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 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02540538
Sponsor's protocol ID
HBnr01
Other IDs
2014-000913-30, 2014
Status last verified
Nov 2018
First submitted
25 Aug 2015
Last updated
19 Dec 2018
Data monitoring committee
Yes

Publications

  • Koc OM, Savelkoul PHM, van Loo IHM, Peeters A, Oude Lashof AML. Safety and immunogenicity of HBAI20 Hepatitis B vaccine in healthy naive and nonresponding adults. J Viral Hepat. 2018 Sep;25(9):1048-1056. doi: 10.1111/jvh.12909. Epub 2018 May 9.

    PubMed 29660190

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HBVaxPro and HBAI20 in people with Hepatitis B, run by Maastricht University Medical Center at 1 site in Netherlands.

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 24 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 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 29 Nov 2018). 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?

Subjects With Local and/or General Adverse Events Irrespective of Severity (time frame: Up to 7 months after first vaccination.). 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 NCT02540538, 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 19 Dec 2018.

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