Study Investigating the Safety and Immunogenicity of AB-729 and VTP 300 in Virologically Suppressed CHB Participants

INTERVENTION: AB‐729 is a GalNAc‐conjugated siRNA inhibitor of hepatitis B virus (HBV). VTP‐300 is an HBV‐specific therapeutic vaccine that uses a prime‐boost platform of ChAdOx1‐HBV followed by MVA‐HBV. Forty participants who are stably virally suppressed on oral tablet nucleos(t)ide analogue (NA) therapy [Tenofovir Disoproxil (TDF), Tenofovir Alafenamide (TAF) or Entecavir (ETV) will receive 60 mg of AB‐729 subcutaneously every 8 weeks (Q8W) for the first 24 weeks plus NA daily. At Week 24 participants will be randomized 1:1 to one of 2 groups (Group A or B) to receive VTP‐300 (intramuscular [IM] administration ChAdOx1‐HBV (2.5 x 10¹°vp) at Week 26, followed by one dose of IM MVA‐HBV [1 x 10 (power 8) pfu] at Week 30 or placebo plus NA. Randomization into Group A or Group B will be stratified by HBsAg level. Participants who experience a pre‐determined decline in HBsAg from Week 26 to Week 34 will receive a second dose of IM MVA‐HBV at Week 38. Participants, investigators and site staff performing safety assessments are blinded to the VTP‐300. AB‐729 and VTP‐300 will be administered in the clinic only. Adherence will be monitored via clinical site staff recording and reporting administration of IP (AB‐729 and VTP‐300) and by subject dosing diary and tablet reconciliation at the site (NAs). At Week 48, all participants will be evaluated for eligibility to discontinue NA therapy based on levels of ALT, HBV DNA, HBeAg and HBsAg. Otherwise they will remain on their NA therapy. Participants who discontinue their NA will be followed for an additional 48 weeks. Participants who do not discontinue their NA will be followed for an additional 24 weeks CONDITION: Infection ‐ Other infectious diseases Virologically‐Suppressed Chronic Hepatitis B; ; Virologically‐Suppressed Chronic Hepatitis B PRIMARY OUTCOME: To evaluate the safety and reactogenicity of AB‐729 followed by VTP‐300 or placebo assessed by eDiary prompts and open‐ended and non leading verbal questions, physical examinations, vital signs, ECG and clinical laboratory assessments (blood counts, chemistry, etc.). ; Vital signs like blood pressure and heart measurements will be assessed by automated device while the participant is in seated or supine position. Same position must be used at every visit. [Treatment Emergent Adverse Events and Lab tests will be collected every 2‐12 weeks from baseline to follow up (96 weeks)] SECONDARY OUTCOME: Assess the HBV specific cellular immune response generated by AB‐729 followed by VTP‐300 or placebo total T cell interferon‐gamma (IFN‐gamma) production induced by the regimens as measured by IFN‐gamma ELISpot[Tests for IFN‐ gamma ELISpot will be collected every 2 – 12 weeks from baseline to follow up (96 weeks)] To characterize the pharmacokinetics (PK) of AB‐729 followed by VTP‐300 or placebo ; Pharmacokinetics parameter includes ; Cmax: Maximum observed plasma concentration ; Tmax: Time of maximum observed plasma concentration ; AUC0‐t: Area under the concentration time‐ curve from the time of dosing to the last measurable concentration ; [Plasma sample collected from all participants at Day 1 (predose, 0.5 hours, 1 hours, 2 hours, 4 hours, 6 hours) and Week 24 (predose, 0.5 hours, 1 hours, 2 hours, 4 hours, 6 hours)] To determine the effect of AB‐729 followed by VTP‐300 or placebo on levels of HBsAg and other viral markers as assessed by change in level of HBsAg and other viral markers ; ; INCLUSION CRITERIA: 1. Adult male or female participants, 18 to 60 years of age, inclusive. 2. Male and female participants are eligible if they agree to use protocol‐defined contraception 3. Body mass index (BMI) greater than 18 kg/m2 and less than 35 kg/m2. 6. HBsAg greater than 100 IU/ml and less than 5,000 IU/mL at Screening. ; Other viral markers include HBV DNA, HBV RNA, hepatitis B virus core‐related antigen (HBcrAg), hepatitis B virus surface antibody (HBsAb), and hepatitis B virus e‐antigen/hepatitis B virus e‐antibody (HBeAg/HBeAb) which are assessed by blood test. [Blood tests will be collected every 2‐12 weeks from baseline to follow up (96 weeks) ] To determine the proportion of participants who experience clinical and/or viral relapse in the follow‐up period after discontinuing NA therapy. ; • Proportion of participants who discontinue NA therapy and subsequently meet protocol‐defined viral relapse criteria as assessed by blood tests and audit of study database[From week 50 to 96 (Post treatment follow up period) ] To determine the proportion of participants who experience clinical and/or viral relapse in the follow‐up period after discontinuing NA therapy. ; • Proportion of participants who discontinue NA therapy and subsequently meet protocol‐defined clinical relapse criteria as assessed by blood tests and audit of study database,[From Week 50 to 96 (Post treatment follow up period) ] To determine the proportion of participants who maintain virologic control during the follow‐up period ; • Proportion of participants who restart NA therapy during the follow‐up period via audit of study database[From week 50 to 96 (Post treatment follow up period)] To determine the proportion of participants who maintain virologic control during the follow‐up period ; • Proportion of participants with HBV DNA less than Low limit of quantification (LLOQ) as assessed by via blood test[From Week 50 to 96 (Post treatment follow up period) ] To determine the proportion of participants who meet protocol defined NA treatment discontinuation by the ALT, HBeAg, HBV DNA and HBsAg levels at Week 48 via blood tests. [Week 48 (end of study treatment)] 4. Documented chronic HBV infection: positive HBsAg, HBV DNA, or HBeAg at least 6 months prior to the Screening Visit (historical documentation must be provided) and negative serum immunoglobulin M (IgM) anti‐hepatitis B core‐related antibody (HBcAb) at the Screening Visit 5. Participants must have HBV DNA less than 20 IU/mL at screening and have been receiving either TAF, TDF, or ETV consistently for greater than 12 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit.. 7. All participants must have assessment of fibrosis demonstrating non‐cirrhotic status.