A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate
Study Details
Study Description
Brief Summary
This study is a single-center, open-label, ascending dose phase 1a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- occurence of solicited local reactogenicity signs and symptoms (AEs) [up to day 63]
numerbers of solicited AEs for 7 days after each vaccination
- occurence of unsolicited local reactogenicity signs and symptoms [up to day 84]
numbers of of unsolicited AEs for 28 days after each vaccination
- changes of safety laboratory measures [up to day 168]
changes of values from safety laboratory measures from baseline
- nature, frequency and severity of adverse events associated with the vaccine [up to day 168]
numbers and severity grade of SAEs throughout the period of the clinical trial
Secondary Outcome Measures
- Magnitude of anti-HBs antibody responses [day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 168]
determined by an accredited serological immuno-assay
- Percentage of participants who seroconvert to anti-HBs (>10 IU/l), anti-HBc or anti-HBs and anti-HBc [day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 168]
determined by an accredited serological immuno-assay
- Magnitude of HBV-specific T-cell responses [day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 168]
determined by cytokine release assays
Eligibility Criteria
Criteria
Key inclusion criteria:
-
Ability to understand the subject information and to personally name, sign and date the informed consent to participate in the clinical trial.
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Provided written informed consent.
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Healthy male and female subjects aged 18-65 years at time of in-formed consent.
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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 measure-ments can be tolerated as they will not increase the risk of the individ-ual having an adverse outcome from participating in this clinical trial as judged by the investigator.
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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.
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Body mass index 18.5-32.0 kg/m2 and weight >50 kg at screening.
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Women of child-bearing potential (WOCBP) only: non-pregnant, non-lactating women with negative pregnancy test.
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WOCBP who agree to comply with the applicable contraceptive re-quirements of the protocol
Key inclusion criteria:
-
Ability to understand the subject information and to personally name, sign and date the informed consent to participate in the clinical trial.
-
Provided written informed consent.
-
Healthy male and female subjects aged 18-65 years at time of informed consent.
-
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.
-
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.
-
Body mass index 18.5-32.0 kg/m2 and weight >50 kg at screening.
-
Women of child-bearing potential (WOCBP) only: non-pregnant, non-lactating women with negative pregnancy test.
-
WOCBP who agree to comply with the applicable contraceptive requirements of the protocol.
Key exclusion criteria:
-
Receipt of any vaccine in the 2 weeks prior to first trial vaccination (4 weeks for live vaccines), during trial or planned receipt of any vaccine in the 3 weeks following last trial vaccination. Exception: Required recommended pandemic vaccines are allowed.
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Previous hepatitis B vaccination or an anti-HBs positive serum status.
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Smallpox vaccination or immunization with a poxvirus-based viral vector or a suspected or confirmed monkeypox infection within the last 10 years.
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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.
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Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccines.
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History of previous HBV infection (serostatus: anti-HBc negative).
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Clinically relevant findings in ECG or significant thromboembolic events in medical history.
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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.
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Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years.
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Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding a febrile seizure as a child and occasional migraine headaches.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CTC North | Hamburg | Germany | 20251 |
Sponsors and Collaborators
- Universitätsklinikum Hamburg-Eppendorf
- German Center for Infection Research
- Clinical Trial Center North (CTC North GmbH)
- Medical Biometry and Epidemiology_- Universitätsklinikum Hamburg Eppendorf
- Helmholtz Zentrum München
- Fraunhofer Gesellschaft
- Institute of Virology Helmholtz Zentrum München (HMGU)
Investigators
- Principal Investigator: Marylyn M Addo, Prof, Universitätsklinikum Hamburg-Eppendorf
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TherVacB_Phase1