A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate

Study Overview
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Brief Summary
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This study is an open-label, ascending dose phase 1a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine

Detailed Description
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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

Official Title
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TherVacB_Phase1a: Open Phase 1a Trial to Assess the Safety and Immunogenicity of a Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate in Healthy Volunteers

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: HEPLISAV B; TherVacB
* Biological: TherVacB


Participation Criteria
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Eligibility Criteria
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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), or planned receipt of any vaccine in the 2 weeks before each trial vaccination (4 weeks for live vaccines) until 3 weeks following each trial vaccination. Exception: Required recommended pandemic and influenza vaccines are allowed. Previous hepatitis B vaccination or an anti-HBs positive serum status before study start. Immunization with a poxvirus-based viral vector. A suspected or confirmed monkeypox infection within the last 10 years. 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. Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccines. History of previous HBV infection (if serostatus: anti-HBc positive). Clinically relevant findings in ECG or significant thromboembolic events in medical history. 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. Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years. Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding a febrile seizure as a child and occasional migraine headaches.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A0<br>HEPLISAV B® and MVA-HBVac high dose | Biological: HEPLISAV B; TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|
| Experimental: Arm B0.1<br>HEPLISAV B® & HBcoreAg low dose and MVA-HBVac low dose | Biological: HEPLISAV B; TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|
| Experimental: Arm B0.2<br>2 x HEPLISAV B® & HBcoreAg medium and MVA-HBVac high dose | Biological: HEPLISAV B; TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|
| Experimental: Arm C0.1<br>HBsAg high dose & HBcoreAg high dose and MVA-HBVac high dose | Biological: TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|
| Experimental: Arm C0.2<br>HBsAg medium dose + adjuvant low dose & HBcoreAg medium dose and MVA-HBVac high dose | Biological: TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|
| Experimental: Arm C0.3<br>HBsAg high dose + adjuvant high dose & HBcoreAg high dose and MVA-HBVac high dose | Biological: TherVacB<br>* Administration of the described combinations via the intramuscular route<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurence of solicited local reactogenicity signs and symptoms (AEs) | numerbers of solicited AEs for 7 days after each vaccination | up to day 63 | 
| occurence of unsolicited local reactogenicity signs and symptoms | numbers of of unsolicited AEs for 28 days after each vaccination | up to day 84 | 
| changes of safety laboratory measures | changes of values from safety laboratory measures from baseline | up to day 224 | 
| nature, frequency and severity of adverse events associated with the vaccine | numbers and severity grade of SAEs throughout the period of the clinical trial | up to day 224 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of anti-HBs antibody responses | determined by an accredited serological immuno-assay | day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224 | 
| Percentage of participants who seroconvert to anti-HBs (>10 IU/l), anti-HBc or anti-HBs and anti-HBc | determined by an accredited serological immuno-assay | day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224 | 
| Magnitude of HBV-specific T-cell responses | determined by cytokine release assays | day 0,day 7,day 28,day 35,day 56,day 63,day 70,day 84,day 224 |