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

TherVacB_Phase1a: Open Phase 1a Trial to Assess the Safety and Immunogenicity of a Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate in Healthy Volunteers

This study is an open-label, ascending dose phase 1a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: HEPLISAV B; TherVacB; Biological: TherVacB

Detailed Description

The clinical trial is divided into two overlapping parts (part I and part II) in 24 healthy male and female subjects aged 18-65 years.

Part I (N = 11) Protein prime vaccinations two times (day 0 and 28) and MVA based boost vaccination 1 x (day 56) 3 subjects will be allocated to A0 and receive HEPLISAV B® and a boost with MVA-HBVac high dose 3 subjects will be allocated to B0.1 and receive HEPLISAV B® & HBcoreAg low dose and a boost with MVA-HBVac low dose 5 subjects will be allocated to B0.2 and receive 2 x HEPLISAV B® & HBcoreAg medium dose and a boost with MVA-HBVac high dose Part II (N = 13) Protein prime vaccinations two times (day 0 and 28) and MVA based boost with MVA-HBVac high dose on day 56 3 subjects will be allocated to C0.1 and receive HBsAg high dose & HBcoreAg high dose plus boost 5 subjects will be allocated to C0.2 and receive HBsAg medium dose + adjuvant low dose & HBcoreAg medium dose plus boost 5 subjects will be allocated to C0.3 and receive HBsAg high dose + adjuvant high dose &HBcoreAg high dose plus boost

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Marylyn M Addo, Prof; Phone Number: +49 40 7410 51102; Email: sekretariataddo@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20359
    • Not yet recruiting
    • Bernhard Nocht Centre for Clinical Trials (BNCCT)
    • Contact: Marylyn M Addo, Prof.Dr.med.; Phone Number: +4940741051102; Email: sekretariataddo@uke.de
  • Munich, Germany, 80802
    • Recruiting
    • Division of Infectious Diseases and Tropical Medicine, LMU Klinikum
    • Contact: Mirjam Schunk, Dr.med.; Email: Mirjam.Schunk@med.uni-muenchen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key inclusion criteria:

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. Healthy male and female subjects aged 18-65 years at time of informed consent.
4. No clinically significant health problems as determined during medical history and physical examination and clinical laboratory results at screening visit. The following laboratory parameters should be within normal limits: WBC, ANC, platelets. AST and ALT should be ≤ULN, CrCL >60mL/min and total bilirubin should not exceed 1,5 x ULN. 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.
5. Participant may be on chronic or as needed medications if, in the opinion of the investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity and do not indicate worsening of a pre-existing medical condition.
6. Body mass index 18.5-32.0 kg/m2 and weight >50 kg at screening.
7. Women of child-bearing potential (WOCBP) only: non-pregnant, non-lactating women with negative pregnancy test.
8. WOCBP who agree to comply with the applicable contraceptive requirements of the protocol.

Key exclusion criteria:

1. Receipt of any vaccine in the 2 weeks prior to first trial vaccination (4 weeks for live vaccines), or planned receipt of any vaccine in the 2 weeks before each trial vaccination (4 weeks for live vaccines) until 3 weeks following each trial vaccination. Exception: Required recommended pandemic and influenza vaccines are allowed.
2. Previous hepatitis B vaccination or an anti-HBs positive serum status before study start.
3. Immunization with a poxvirus-based viral vector. A suspected or confirmed monkeypox infection within the last 10 years.
4. Known allergy to components of the vaccine products (incl. hypersensitivity to yeast) or history of life-threatening reactions to vaccines containing one of the substances.
5. Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccines.
6. History of previous HBV infection (if serostatus: anti-HBc positive).
7. Clinically relevant findings in ECG or significant thromboembolic events in medical history.
8. 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 pro-ducts.
9. Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years.
10. Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding a febrile seizure as a child and occasional migraine headaches.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A0; HEPLISAV B® and MVA-HBVac high dose	Biological: HEPLISAV B; TherVacB; Administration of the described combinations via the intramuscular route
Experimental: Arm B0.1; HEPLISAV B® & HBcoreAg low dose and MVA-HBVac low dose	Biological: HEPLISAV B; TherVacB; Administration of the described combinations via the intramuscular route
Experimental: Arm B0.2; 2 x HEPLISAV B® & HBcoreAg medium and MVA-HBVac high dose	Biological: HEPLISAV B; TherVacB; Administration of the described combinations via the intramuscular route
Experimental: Arm C0.1; HBsAg high dose & HBcoreAg high dose and MVA-HBVac high dose	Biological: TherVacB; Administration of the described combinations via the intramuscular route
Experimental: Arm C0.2; HBsAg medium dose + adjuvant low dose & HBcoreAg medium dose and MVA-HBVac high dose	Biological: TherVacB; Administration of the described combinations via the intramuscular route
Experimental: Arm C0.3; HBsAg high dose + adjuvant high dose & HBcoreAg high dose and MVA-HBVac high dose	Biological: TherVacB; Administration of the described combinations via the intramuscular route

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurence of solicited local reactogenicity signs and symptoms (AEs)	numerbers of solicited AEs for 7 days after each vaccination	up to day 63
occurence of unsolicited local reactogenicity signs and symptoms	numbers of of unsolicited AEs for 28 days after each vaccination	up to day 84
changes of safety laboratory measures	changes of values from safety laboratory measures from baseline	up to day 224
nature, frequency and severity of adverse events associated with the vaccine	numbers and severity grade of SAEs throughout the period of the clinical trial	up to day 224

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of anti-HBs antibody responses	determined by an accredited serological immuno-assay	day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224
Percentage of participants who seroconvert to anti-HBs (>10 IU/l), anti-HBc or anti-HBs and anti-HBc	determined by an accredited serological immuno-assay	day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224
Magnitude of HBV-specific T-cell responses	determined by cytokine release assays	day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: Helmholtz Zentrum München; LMU Klinikum; German Center for Infection Research; Medical Biometry and Epidemiology_- Universitätsklinikum Hamburg Eppendorf; Fraunhofer Gesellschaft; Institute of Virology Helmholtz Zentrum München (HMGU); Monipol Deutschland GmbH
• Investigators: Principal Investigator: Marylyn M Addo, Prof, Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: November 6, 2022
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic
• Other Study ID Numbers: TherVacB_Phase1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No