Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001

Study to Evaluate the Induction of HBV Virus Neutralizing Antibodies in Healthy Vaccine Naive Adults and Non-responders and in Patients Chronically Infected With HBV Using VVX001

The Study will evaluate the effects of VVX001, a novel vaccine for hepatitis B, to

• elicit a robust protective IgG immune response in vaccine naive subjects
• in subjects who failed to demonstrate seroconversion after treatment with a licensed hepatitis B vaccine and
• in patients chronically infected with HBV.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: VVX001; Biological: Placebo

Detailed Description

VVX001 is a recombinant fusion Protein composed of PreS from the large surface antigen of HBV and Peptides derived from the grass pollen allergen Phl p 5. In a previous trial in allergic but otherwise healthy subjects the product has been shown to elicit a potent IgG response to the epitope of PreS1, which is responsible for binding to the cellular receptor NTCP. These antibodies prevent infection with HBV in a cell culture model. The present study will evaluate if such an immune response can also be achieved in four different patient populations: 1) vaccine naive subjects; 2) subjects having failed to seroconvert upon vaccination with a licensed HBV vaccine; 3) patients who are chronically infected with HBV, but are classified as inactive carriers; 4) patients with active chronic HBV infection who are HbEAg negative and chronically treated with nucleo(t)side (NUC) antiviral drugs. All subjects will receive 5 s.c. injections of VVX001, the time course of antibody response to PreS1 will be monitored in all of them. In cohort 4) NUC treatment will be withdrawn at different timepoints during the study and the effect of treatment with VVX001 on hepatitis B disease Parameters will be monitored. Subjects will be followed for 6 months after the of treatment for Evaluation of a long-term effect.

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Helmut Brunar, PhD; Phone Number: +43 664 415 9511; Email: h.brunar@viravaxx.com
• Study Contact Backup: Name: Ghazaleh Gouya, MD; Phone Number: +43 650 470 4206; Email: gouya@gouya-insights.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Medical University of Graz
    • Contact: Rudolf Stauber, MD; Phone Number: +43 316 385 80268; Email: rudolf.stauber@medunigraz.at
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Ursula Wiedermann, MD; Phone Number: +43 1 40160 38290; Email: ursula.wiedermann@meduniwien.ac.at
    • Contact: Petra Munda, MD; Phone Number: +43 1 40400 4741; Email: petra.munda@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cohort 1: hepatits B vaccine naive subjects Seronegative for anti-HBs and anti-HBc antibodies and for HBs Antigen
• Cohort 2: Subjects who failed to develop a protective immune response upon standard vaccination with a licensed hepatitis B vaccine (<10 IU/L anti HbS antibodies) Seronegative for anti-HbS (<10 IU/L) and anti-HBc antibodies and for HbSAg

• Cohort 3: Parameters confirmed at screening during the past 12 months

  1. HBeAg negative;
  2. HbSAg positive at screening <3000 IU/ml;
  3. HBV viral load <2000 IU/ml
  4. ALT Levels ≤ULN at screening

• Cohort 4a: Parameters confirmed at screening during the last 12 months

  1. HBeAg negative;
  2. HbSAg positive <1000 IU/ml
  3. HBV DNA not detectable for at least 2 years
  4. History of nucleos(t)die Treatment for at least 3 years
  5. Willingness to discontinue NUC treatment during study
  6. ALT levels ≤ULN at screening

• Cohort 4b: in addition to cohort 4a:

  1. willingness to discontinue NUC treatment 6 weeks before entering the Study

  2. ALT Levels ≤ULN 6 weeks before entering the study and

     • 5x ULN at screening

Exclusion Criteria:

• Pregnant or breast-feeding females, adequate contraception required during the treatment phase
• History of grass pollen allergy
• Co-infection with HCV, HDV, HIV
• History of auto-immune hepatitis
• Elevated Levels of Alpha-Fetoprotein (AFP) >100 ng/ml
• Documented history of decompensated liver disease (albumin <3.5 g/dl and bilirubin >1.3 mg/dl)
• Autoimmune disorders, transplant recipients, use of immunosuppressive or immune modulating agents
• Oral corticosteroids of 20 mg/week within the past 4 weeks prior to screening
• History of treatment with PEG-IFN of IFN for at least 1 year prior to screening
• History of evidence or conditions associated with chronic liver disease
• Acute fever at time of enrolment
• History of alcohol abuse
• Planned administration of a vaccine not foreseen by study protocol in the period starting 30 days before first product administration and during the entire study period with exception of influenza vaccine
• History of Cancer
• Other severe co-morbid conditions and concurrent medication making the subject unsuitable for participation
• blood or plasma donation within 1 month of study enrolement and during the course of the study

• For all patients with chronic HBV infection:

  1. Total bilirubin >2x ULN confirmed by repeat testing within 2 weeks, unless historical documentation of Gilbert's syndrome
  2. Documented or suspected hepatocelluar carcinoma
  3. Presence of cholangitis, cholecystitis or bile duct obstruction
  4. Liver cirrhosis assessed by fibroscan with elastography <9kPa within the previous 12 months and FIB-score <3.2 at study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: VVX001 (20 micrograms); Subjects will receive 5 injections of 20 micrograms each over a period of 4 months	Biological: VVX001; 5 s.c. injections of 20 micrograms of VVX001 four weeks apart
PLACEBO_COMPARATOR: Placebo; Subjects will receive 5 s.c. injections of matching placebo over a period of 4 months	Biological: Placebo; 5 s.c. injections of matching Placebo four weeks apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PreS specific IgG antibodies	Titer of PreS specific IgG antibodies	4 weeks after the last injection of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PreS specific IgG, IgG1 and IgG4 antibodies	Titers of PreS specific IgG, IgG1 and IgG4 antibodies	4 weeks and 6 months after the last injection of study drug
HbSAg specific antibodies	Titers of HbSAg specific antibodies	4 weeks and 6 months after the last injection of study drug
Suppression of HBV infection	Suppression of HBV infection in HepG2-NTCP cells using HBV strain D3 in cell culture with patient sera	4 weeks and 6 months after the last injection of study drug
T cell proliferation	Proliferation of PreS specific CD4 and CD8 T cells	4 weeks and 6 months after the last injection of study drug
HbSAg titers	HbS Antigen titers will be measured in chronically infected patients	4 weeks and 6 months after the last injection of study drug
HBV DNA load	HBV DNA load will be measured by PCR in chronically infected patients	4 weeks and 6 months after the last injection of study drug
HBVcrAg titers	HBVcrAG titers will be measured in chronically infected patients	4 weeks and 6 months after the last injection of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Frequency, intensity and relatedness of adverse events	up to 52 weeks

Collaborators and Investigators

• Sponsor: Viravaxx AG
• Collaborators: Gouya Insights; KKS MedUni Vienna
• Investigators: Principal Investigator: Petra Munda, MD, Medical University Vienna

Publications and helpful links

General Publications

• Cornelius C, Schoneweis K, Georgi F, Weber M, Niederberger V, Zieglmayer P, Niespodziana K, Trauner M, Hofer H, Urban S, Valenta R. Immunotherapy With the PreS-based Grass Pollen Allergy Vaccine BM32 Induces Antibody Responses Protecting Against Hepatitis B Infection. EBioMedicine. 2016 Sep;11:58-67. doi: 10.1016/j.ebiom.2016.07.023. Epub 2016 Aug 8.
• Tulaeva I, Cornelius C, Zieglmayer P, Zieglmayer R, Schmutz R, Lemell P, Weber M, Focke-Tejkl M, Karaulov A, Henning R, Valenta R. Quantification, epitope mapping and genotype cross-reactivity of hepatitis B preS-specific antibodies in subjects vaccinated with different dosage regimens of BM32. EBioMedicine. 2020 Sep;59:102953. doi: 10.1016/j.ebiom.2020.102953. Epub 2020 Aug 24.

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 6, 2018
• Primary Completion (ANTICIPATED): September 30, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (ACTUAL): August 10, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: VVX001-CS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No