This study is an open-label, ascending dose phase 1b/2a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.
This is a multi-centre study conducted in 81 participants. The clinical trial is divided into two overlapping parts (part A and B). All treatment groups of Part A will receive a single dose of HEPLISAV B on Day 1 and Day 29 and MVA-HBVac on Day 56. From study arm A2 on all participants also receive HBcoreAg, in a low dose in arms A2 and A3 and in a medium dose in arm A4. In arms A5 and A6 either the low or the medium dose will be applied to an extended number of participants. The MVA-HBVac booster dose will be given in a dose-escalating way with a low dose in arms A1 and A2 and a high dose in arms A3, A4, A5 and A6. The treatment group in Part B, study arm B1 will receive two doses of HEPLISAV B together with HBcoreAg in a high dose (on day 1 and 29), and a high booster dose of MVA-HBVac on day 56. In arm B2 either the regimen of B1 or A5 will be applied to an extended number of participants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
81
Administration of the described combinations via the intramuscular route
Administration of the described combinations via the intramuscular route
Investigational Site GUF
Frankfurt, Germany
Investigational Site UKE
Hamburg, Germany
Investigational Site MHH
Hanover, Germany
Investigational Site Uni Leipzig
Leipzig, Germany
Frequencies and magnitudes of unsolicited adverse events
Reported numbers and severity grade of unsolicited AEs for 28 days after each vaccination
Time frame: up to day 84
Frequencies and magnitudes of serious adverse events (SAEs) throughout the trial period
Reported numbers and types of SAEs throughout the period of the clinical trial
Time frame: up to day 224
Frequencies and magnitudes of adverse event of special interest (AESI) and Suspected Unexpected Serious Adverse Reaction (SUSAR) throughout the trial period
Reported numbers and severity grade of AESIs and numbers and types of SUSARs
Time frame: up to day 224
Frequencies and magnitudes of solicited local reactogenicity signs and symptoms within 7 days after each vaccination
Reported numbers and severity of solicited AEs
Time frame: up to day 63
Frequencies and magnitudes of solicited systemic reactogenicity signs and symptoms within 7 days after each vaccination
Reported numbers and severity of solicited AEs
Time frame: up to day 63
Frequencies and magnitudes of liver toxicity (ALT flare-ups) stratified by severity throughout the trial period
Reported numbers and severity grade of AESIs
Time frame: up to day 224
Change from baseline of safety laboratory measurements throughout the trial period
Changes of values from safety laboratory measurements from baseline
Time frame: up to day 224
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Investigational Site LMU
Munich, Germany
Investigational Site TUM
Munich, Germany
Frequency of subjects with HBsAg drop below the lower limit of quantification
Determined by an accredited serological immuno-assay
Time frame: 2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit).
Frequency of subjects with a ≥ 1 log10 drop in HBsAg titers from day 0 (start of study medication) with the goal of 30% of patients achieving a ≥ 1log10 HBsAg drop
Determined by an accredited serological immuno-assay
Time frame: 2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit
Frequency of subjects with an induction of anti-HBs titers ≥ 10 IU/L
Determined by an accredited serological immuno-assay
Time frame: 2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit
Frequency of subjects developing any anti-HBs antibody response
Determined by an accredited serological immuno-assay
Time frame: 2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit
Frequency of subjects with an increased signal in the HBV-specific cytokine-secretion assay compared to pretreatment values
Determined by cytokine release assays
Time frame: 2 weeks (Day 70), 2 months (Day 112) and 6 months (Day 224) after completion of the vaccination regimen (last study visit