Assessment of the safety and efficacy of a hepatitis B vaccine in adult patients with hepatitis B

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum der Universitaet Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

26 May 2025 → ongoing

Decision date (initial)

2024-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Union’s Horizon 2020 research and innovation programme under grant agreement no 848223

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess safety and tolerability of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine candidate (TherVacB)
• Safety and tolerability of the vaccine components of the TherVacB vaccination scheme
• Safety and tolerability of the TherVacB vaccination scheme in terms of liver toxicity

Secondary objectives 2

1. Evaluation of the antiviral effect of the TherVacB vaccination scheme
2. Evaluation of the immunogenicity of the vaccine components and the TherVacB vaccination scheme

Conditions and MedDRA coding

Chronic hepatitis B

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Paul-Ehrlich-Institut, Paul-Ehrlich-Institut, Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ability to understand the subject information and to personally name, sign and date the informed consent to participate in the clinical trial.
2. Provided written informed consent.
3. Confirmed chronic hepatitis B virus (HBV) infection (CHB) that fulfills the following criteria: - HBsAg positive for ≥ 6 months - Anti-HBs negative - HBsAg levels 100-2000 IU/mL - HBV nucleos(t)ide analog (NUC) treatment for ≥ 6 months - HBV load < 100 IU/ml at least twice within the last 6 months
4. Males and non-pregnant, non-lactating female with negative pregnancy test aged 18-70 years at time of informed consent.
5. Apart from CHB no other clinically significant health problems as determined during medical history and physical examination and clinical laboratory results at the screening visit. The following abnormal laboratory parameters will be permitted: - leukocyte count ≥ 2.500/µl - platelet count ≥ 150.000/µl - ALT elevation ≤ 60 U/L - AST should be ≤ 40 U/L - bilirubin should be ≤ ULN - INR should be ≤ ULN - CrCL > 60mL/min. Non-clinically significant, minor deviations of laboratory measurements can be tolerated as they will not increase the risk of the individual having an adverse outcome from participating in this clinical trial as judged by the investigator.
6. Subject may be on chronic or as needed medications if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate worsening of a pre-existing medical condition.
7. Body mass index 18.5-32.0 kg/m2 and weight >50 kg at screening.

Exclusion criteria 20

1. Advanced liver fibrosis or cirrhosis (demonstrated by ultrasound or transient elastography ≥8 kP in fasting condition)
2. Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccines.
3. Clinically relevant findings in ECG or significant thromboembolic events in medical history.
4. Evidence for a condition in the subject’s medical history or during medical examination that might influence either the safety of the subject or the absorption, distribution, metabolism or excretion of vaccine products.
5. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the first dose of the trial vaccine.
6. Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 3 years.
7. Any treatment with immunosuppressants or other immune-modifying drugs (including, but not limited to systemic corticosteroids, biologicals and Methotrexate) within the last 3 years. Exception: topical corticosteroids, e.g. occasional asthma spays or systemic corticosteroids for medical emergencies.
8. Any chronic or active neurologic disorder, including diagnosis of migraine, seizures and epilepsy. Exception: a febrile seizure as a child and occasional headaches.
9. Participation in a clinical investigation within the past 4 weeks or five times the half-life of the previously taken IMP.
10. Investigator or employee of the study site with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, natural or adopted child) of the investigator or employee with direct involvement in the proposed study.
11. Subjects who are known or suspected • not to comply with the clinical trial directives. • not to be reliable or trustworthy. • not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they would agree to be exposed.
12. WOCBP who don’t agree to comply with the applicable contraceptive requirements of the protocol
13. History of hepatocellular carcinoma
14. Coinfection with Hepatitis C Virus (HCV) (RNA positive), Human Immunodeficiency Virus (HIV) or Hepatitis Delta virus (anti-Delta positive)
15. Regular alcohol intake >30 g/d (male), >20 g/d (female) or any other known drug addiction.
16. Donation of blood or blood products (e.g., 450 mL or more of plasma or platelets) within 60 days prior to receiving the first dose of the investigational medicinal product (IMP).
17. Receipt of any vaccine in the 2 weeks prior to first trial vaccination (4 weeks for live vaccines), during trial or planned receipt of any vaccine in the 3 weeks following last trial vaccination. Exception: Required recommended pandemic vaccines or emergency vaccines (e.g., tetanus) are allowed.
18. Known allergy to components of the vaccine products as referred in Table 6 (incl. hypersensitivity to yeast components, E.coli proteins or lipids, duck’s or hen’s egg white, penicillin, streptomycin, kanamycin) or history of life-threatening reactions to vaccines containing one of the substances.
19. Known liver disease other than hepatitis B
20. Previous receipt of an MVA based vaccine (e.g. as part of previous MVA studies, monkeypox or smallpox vaccination )

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Frequencies and magnitudes of unsolicited adverse events
2. Frequencies and magnitudes of serious adverse events (SAEs)
3. Frequencies and magnitudes of adverse events of special interest (AESI) and Suspected Unexpected Serious Adverse Reactions (SUSAR)
4. Frequencies and magnitudes of solicited local reactogenicity signs and symptoms within 7 days after each vaccination
5. Frequencies and magnitudes of solicited systemic reactogenicity signs and symptoms within 7 days after each vaccination
6. Frequencies and magnitudes of liver toxicity (ALT flare-ups) stratified by severity
7. Change from baseline of safety laboratory measurements

Secondary endpoints 7

1. Frequency of subjects with HBsAg drop below the lower limit of quantification
2. Frequency of subjects with a ≥ 1 log10 drop in HBsAg titers from day 0 (start of study medication) with the goal of 30% of patients achieving a ≥ 1log10 HBsAg drop
3. Frequency of subjects with an induction of anti-HBs titers ≥10 IU/L
4. Frequency of subjects developing any anti-HBs antibody response
5. Frequency of subjects with an increased signal in the HBV-specific cytokine-secretion assay compared to pretreatment values
6. Frequency of subjects with an increased frequency of total HBV-specific, cytokine-secreting T cells compared to pretreatment values
7. Frequency of subjects developing an immune response to TherVacB treatment arms A5, A6 or B4 with the goal of ≥ 30% of patients developing anti-HBs antibody or T-cell responses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Universitaet Muenchen AöR

Sponsor organisation

Klinikum der Universitaet Muenchen AöR

Address

Leopoldstrasse 5, Maxvorstadt Maxvorstadt

City

Munich

Postcode

80802

Country

Germany

Scientific contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

International Clinical Trials Unit (iCTU)

Public contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

International Clinical Trials Unit (iCTU)

Third parties 7

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications