Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001

• ClinicalTrials.gov Identifier: NCT03625934
• Recruitment Status: Recruiting
• First Posted: August 10, 2018
• Last Update Posted: April 6, 2021
• Sponsor: Viravaxx AG
• Collaborators: Gouya Insights; KKS MedUni Vienna
• Information provided by (Responsible Party): Viravaxx AG

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis B	Biological: VVX001; Biological: Placebo	Phase 2

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 In cohort 4) NUC treatment will be withdrawn at different timepoints during the study and the effect of treatment with VVX001 on hepatitis B disease Parameters will be monitored.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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 6, 2018
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. PreS specific IgG antibodies [ Time Frame: 4 weeks after the last injection of study drug ]
   Titer of PreS specific IgG antibodies

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Adverse events [ Time Frame: up to 52 weeks ]
   Frequency, intensity and relatedness of adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Helmut Brunar, PhD; +43 664 415 9511; h.brunar@viravaxx.com

Contact: Ghazaleh Gouya, MD; +43 650 470 4206; gouya@gouya-insights.com

Locations

Austria

Medical University of Graz; Recruiting

Graz, Austria, 8036

Contact: Rudolf Stauber, MD +43 316 385 80268 rudolf.stauber@medunigraz.at

Medical University of Vienna; Recruiting

Vienna, Austria, 1090

Contact: Ursula Wiedermann, MD +43 1 40160 38290 ursula.wiedermann@meduniwien.ac.at

Contact: Petra Munda, MD +43 1 40400 4741 petra.munda@meduniwien.ac.at

Sponsors and Collaborators

Viravaxx AG

Gouya Insights

KKS MedUni Vienna

Investigators

• Principal Investigator: Petra Munda, MD; Medical University Vienna

More Information

Additional Information:

Sponsor website 

Publications:

Cornelius C, Schöneweis 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.

• Responsible Party: Viravaxx AG
• ClinicalTrials.gov Identifier: NCT03625934
• Other Study ID Numbers: VVX001-CS001
• First Posted: August 10, 2018
• Last Update Posted: April 6, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human