Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001

NCT ID: NCT03625934

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-06
• Study Completion Date: 2023-12-31

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.

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 In cohort 4) NUC treatment will be withdrawn at different timepoints during the study and the effect of treatment with VVX001 on hepatitis B disease Parameters will be monitored.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

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

VVX001 (20 micrograms)

Subjects will receive 5 injections of 20 micrograms each over a period of 4 months

Group Type: EXPERIMENTAL

VVX001

Intervention Type: BIOLOGICAL

5 s.c. injections of 20 micrograms of VVX001 four weeks apart

Placebo

Subjects will receive 5 s.c. injections of matching placebo over a period of 4 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

5 s.c. injections of matching Placebo four weeks apart

Interventions

VVX001

5 s.c. injections of 20 micrograms of VVX001 four weeks apart

Intervention Type: BIOLOGICAL

Placebo

5 s.c. injections of matching Placebo four weeks apart

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gouya Insights

UNKNOWN

Sponsor Role: collaborator

KKS MedUni Vienna

UNKNOWN

Sponsor Role: collaborator

Viravaxx AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petra Munda, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna

Locations

Medical University of Graz

Graz, , Austria

Site Status: RECRUITING

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Helmut Brunar, PhD

Role: CONTACT

h.brunar@viravaxx.com

+43 664 415 9511

Ghazaleh Gouya, MD

Role: CONTACT

gouya@gouya-insights.com

+43 650 470 4206

Facility Contacts

Rudolf Stauber, MD

Role: primary

rudolf.stauber@medunigraz.at

+43 316 385 80268

Ursula Wiedermann, MD

Role: primary

ursula.wiedermann@meduniwien.ac.at

+43 1 40160 38290

Petra Munda, MD

Role: backup

petra.munda@meduniwien.ac.at

+43 1 40400 4741

References

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.

Reference Type: BACKGROUND

PMID: 27568223 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32855110 (View on PubMed)

Related Links

http://www.viravaxx.com

Sponsor website

Other Identifiers

VVX001-CS001

Identifier Type: -

Identifier Source: org_study_id