TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate

NCT06513286 | Recruiting Phase 1 DMC

• 1 other identifier: TherVacB_1b2a_1
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 6

Brief Summary

This study is an open-label, ascending dose phase 1b/2a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (7)

• Frequencies and magnitudes of unsolicited adverse events

  Reported numbers and severity grade of unsolicited AEs for 28 days after each vaccination

  up to day 84

• Frequencies and magnitudes of serious adverse events (SAEs) throughout the trial period

  Reported numbers and types of SAEs throughout the period of the clinical trial

  up to day 224

• Frequencies and magnitudes of adverse event of special interest (AESI) and Suspected Unexpected Serious Adverse Reaction (SUSAR) throughout the trial period

  Reported numbers and severity grade of AESIs and numbers and types of SUSARs

  up to day 224

• Frequencies and magnitudes of solicited local reactogenicity signs and symptoms within 7 days after each vaccination

  Reported numbers and severity of solicited AEs

  up to day 63

• Frequencies and magnitudes of solicited systemic reactogenicity signs and symptoms within 7 days after each vaccination

  Reported numbers and severity of solicited AEs

  up to day 63

• Frequencies and magnitudes of liver toxicity (ALT flare-ups) stratified by severity throughout the trial period

  Reported numbers and severity grade of AESIs

  up to day 224

• Change from baseline of safety laboratory measurements throughout the trial period

  Changes of values from safety laboratory measurements from baseline

  up to day 224

Secondary Outcomes (5)

• Frequency of subjects with HBsAg drop below the lower limit of quantification

  2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit).

• 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

  2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit

• Frequency of subjects with an induction of anti-HBs titers ≥ 10 IU/L

  2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit

• Frequency of subjects developing any anti-HBs antibody response

  2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit

• Frequency of subjects with an increased signal in the HBV-specific cytokine-secretion assay compared to pretreatment values

  2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit

Study Arms (8)

Arm A1

EXPERIMENTAL

HEPLISAV B® (low dose) and MVA-HBVac (low dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm A2

EXPERIMENTAL

HEPLISAV B® (low dose) \& HBcoreAg (low dose) and MVA-HBVac (low dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm A3

EXPERIMENTAL

HEPLISAV B® (low dose) \& HBcoreAg (low dose) and MVA-HBVac (high dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm A4

EXPERIMENTAL

HEPLISAV B® (low dose) \& HBcoreAg (medium dose) and MVA-HBVac (high dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm A5 (Europe)

EXPERIMENTAL

HEPLISAV B® (low dose) \& HBcoreAg (low dose) and MVA-HBVac (high dose) or HEPLISAV B® (low dose) \& HBcoreAg (medium dose) and MVA-HBVac (high dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm A6 (Tanzania)

EXPERIMENTAL

HEPLISAV B® (low dose) \& HBcoreAg (low dose) and MVA-HBVac (high dose) or HEPLISAV B® (low dose) \& HBcoreAg (medium dose) and MVA-HBVac (high dose)

Biological: TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac)

Arm B1

EXPERIMENTAL

HEPLISAV B® (high dose) \& HBcoreAg (high dose) and MVA-HBVac (high dose)

Biological: TherVacB (2xHEPLISAV B + HBcoreAg + MVA-HBVac)

Arm B2

EXPERIMENTAL

HEPLISAV B® (high dose) \& HBcoreAg (high dose) and MVA-HBVac (high dose) or regimen of study arm A5

Biological: TherVacB (2xHEPLISAV B + HBcoreAg + MVA-HBVac)

Interventions

TherVacB (2xHEPLISAV B + HBcoreAg + MVA-HBVac) BIOLOGICAL

Administration of the described combinations via the intramuscular route

Arm B1; Arm B2

TherVacB (HEPLISAV B +/- HBcoreAg + MVA-HBVac) BIOLOGICAL

Administration of the described combinations via the intramuscular route

Arm A1; Arm A2; Arm A3; Arm A4; Arm A5 (Europe); Arm A6 (Tanzania)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand the subject information and to personally name, sign and date the informed consent to participate in the clinical trial.
• Provided written informed consent.
• 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
• Males and non-pregnant, non-lactating female with negative pregnancy test aged 18-70 years at time of informed consent.
• 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

You may not qualify if:

• Known liver disease other than hepatitis B
• Advanced liver fibrosis or cirrhosis (demonstrated by ultrasound or transient elastography ≥8 kP in fasting condition)
• WOCBP who don't agree to comply with the applicable contraceptive requirements of the protocol
• History of hepatocellular carcinoma
• Coinfection with Hepatitis C Virus (HCV) (RNA positive), Human Immunodeficiency Virus (HIV) or Hepatitis Delta virus (anti-Delta positive)
• Regular alcohol intake \>30 g/d (male), \>20 g/d (female) or any other known drug addiction.
• 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).
• 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.
• Previous receipt of an MVA based vaccine (e.g. as part of previous MVA studies, monkeypox or smallpox vaccination)
• 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.
• Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccines.
• Clinically relevant findings in ECG or significant thromboembolic events in medical history.
• 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.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the first dose of the trial vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 3 years.

Sponsors & Collaborators

• Michael Hoelscher: lead
• Institute of Virology Helmholtz Zentrum München Trogerstraße 30 81675 Munich, Germany: collaborator

Study Sites (6)

Investigational Site GUF

Frankfurt, 60590, Germany

RECRUITING

Investigational Site UKE

Hamburg, 20246, Germany

RECRUITING

Investigational Site MHH

Hanover, 30625, Germany

NOT YET RECRUITING

Investigational Site Uni Leipzig

Leipzig, 04103, Germany

RECRUITING

Investigational Site LMU

Munich, 81337, Germany

RECRUITING

Investigational Site TUM

Munich, 81675, Germany

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Hoelscher, Prof. Dr. med.

  Division of Infectious Diseases and Tropical Medicine, LMU Klinikum

  STUDY CHAIR

Central Study Contacts

Otto Geisenberger, Dr.rer.nat.

CONTACT

+49-89-4400598; otto.geisenberger@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Dr. M. Hoelscher

Study Record Dates

• First Submitted: June 11, 2024
• First Posted: July 22, 2024
• Study Start: June 12, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6)