Back to resultsStudy to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001
Primary Purpose
Hepatitis B
Status
Recruiting
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
VVX001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B
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
- HBeAg negative;
- HbSAg positive at screening <3000 IU/ml;
- HBV viral load <2000 IU/ml
- ALT Levels ≤ULN at screening
Cohort 4a: Parameters confirmed at screening during the last 12 months
- HBeAg negative;
- HbSAg positive <1000 IU/ml
- HBV DNA not detectable for at least 2 years
- History of nucleos(t)die Treatment for at least 3 years
- Willingness to discontinue NUC treatment during study
- ALT levels ≤ULN at screening
Cohort 4b: in addition to cohort 4a:
- willingness to discontinue NUC treatment 6 weeks before entering the Study
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:
- Total bilirubin >2x ULN confirmed by repeat testing within 2 weeks, unless historical documentation of Gilbert's syndrome
- Documented or suspected hepatocelluar carcinoma
- Presence of cholangitis, cholecystitis or bile duct obstruction
- Liver cirrhosis assessed by fibroscan with elastography <9kPa within the previous 12 months and FIB-score <3.2 at study entry
Sites / Locations
- Medical University of GrazRecruiting
- Medical University of ViennaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
VVX001 (20 micrograms)
Placebo
Arm Description
Subjects will receive 5 injections of 20 micrograms each over a period of 4 months
Subjects will receive 5 s.c. injections of matching placebo over a period of 4 months
Outcomes
Primary Outcome Measures
PreS specific IgG antibodies
Titer of PreS specific IgG antibodies
Secondary Outcome Measures
PreS specific IgG, IgG1 and IgG4 antibodies
Titers of PreS specific IgG, IgG1 and IgG4 antibodies
HbSAg specific antibodies
Titers of HbSAg specific antibodies
Suppression of HBV infection
Suppression of HBV infection in HepG2-NTCP cells using HBV strain D3 in cell culture with patient sera
T cell proliferation
Proliferation of PreS specific CD4 and CD8 T cells
HbSAg titers
HbS Antigen titers will be measured in chronically infected patients
HBV DNA load
HBV DNA load will be measured by PCR in chronically infected patients
HBVcrAg titers
HBVcrAG titers will be measured in chronically infected patients
Full Information
NCT ID
NCT03625934
First Posted
July 2, 2018
Last Updated
April 2, 2021
Sponsor
Viravaxx AG
Collaborators
Gouya Insights, KKS MedUni Vienna
1. Study Identification
Unique Protocol Identification Number
NCT03625934
Brief Title
Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 6, 2018 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Viravaxx AG
Collaborators
Gouya Insights, KKS MedUni Vienna
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VVX001 (20 micrograms)
Arm Type
Experimental
Arm Description
Subjects will receive 5 injections of 20 micrograms each over a period of 4 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive 5 s.c. injections of matching placebo over a period of 4 months
Intervention Type
Biological
Intervention Name(s)
VVX001
Intervention Description
5 s.c. injections of 20 micrograms of VVX001 four weeks apart
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
5 s.c. injections of matching Placebo four weeks apart
Primary Outcome Measure Information:
Title
PreS specific IgG antibodies
Description
Titer of PreS specific IgG antibodies
Time Frame
4 weeks after the last injection of study drug
Secondary Outcome Measure Information:
Title
PreS specific IgG, IgG1 and IgG4 antibodies
Description
Titers of PreS specific IgG, IgG1 and IgG4 antibodies
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
HbSAg specific antibodies
Description
Titers of HbSAg specific antibodies
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
Suppression of HBV infection
Description
Suppression of HBV infection in HepG2-NTCP cells using HBV strain D3 in cell culture with patient sera
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
T cell proliferation
Description
Proliferation of PreS specific CD4 and CD8 T cells
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
HbSAg titers
Description
HbS Antigen titers will be measured in chronically infected patients
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
HBV DNA load
Description
HBV DNA load will be measured by PCR in chronically infected patients
Time Frame
4 weeks and 6 months after the last injection of study drug
Title
HBVcrAg titers
Description
HBVcrAG titers will be measured in chronically infected patients
Time Frame
4 weeks and 6 months after the last injection of study drug
Other Pre-specified Outcome Measures:
Title
Adverse events
Description
Frequency, intensity and relatedness of adverse events
Time Frame
up to 52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
HBeAg negative;
HbSAg positive at screening <3000 IU/ml;
HBV viral load <2000 IU/ml
ALT Levels ≤ULN at screening
Cohort 4a: Parameters confirmed at screening during the last 12 months
HBeAg negative;
HbSAg positive <1000 IU/ml
HBV DNA not detectable for at least 2 years
History of nucleos(t)die Treatment for at least 3 years
Willingness to discontinue NUC treatment during study
ALT levels ≤ULN at screening
Cohort 4b: in addition to cohort 4a:
willingness to discontinue NUC treatment 6 weeks before entering the Study
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:
Total bilirubin >2x ULN confirmed by repeat testing within 2 weeks, unless historical documentation of Gilbert's syndrome
Documented or suspected hepatocelluar carcinoma
Presence of cholangitis, cholecystitis or bile duct obstruction
Liver cirrhosis assessed by fibroscan with elastography <9kPa within the previous 12 months and FIB-score <3.2 at study entry
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Helmut Brunar, PhD
Phone
+43 664 415 9511
Email
h.brunar@viravaxx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ghazaleh Gouya, MD
Phone
+43 650 470 4206
Email
gouya@gouya-insights.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Petra Munda, MD
Organizational Affiliation
Medical University Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rudolf Stauber, MD
Phone
+43 316 385 80268
Email
rudolf.stauber@medunigraz.at
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ursula Wiedermann, MD
Phone
+43 1 40160 38290
Email
ursula.wiedermann@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Petra Munda, MD
Phone
+43 1 40400 4741
Email
petra.munda@meduniwien.ac.at
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27568223
Citation
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.
Results Reference
background
PubMed Identifier
32855110
Citation
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.
Results Reference
background
Links:
URL
http://www.viravaxx.com
Description
Sponsor website
Learn more about this trial
Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001
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