ANRS HB07 IP-Cure-B Proof of Concept (PoC) Clinical Trial. Educating the Liver Immune Environment Through TLR8 Stimulation Followed by NUC Discontinuation

Inclusion Criteria: 1. Patients with HBeAg negative CHB on documented NUC for ≥ 3 years with HBV DNA LLOQ by local assay by polymerase chain reaction (PCR) documented at least annually over the last 3 years. NUC can include only tenofovir disoproxil fumarate (TDF), tenofovir alafemanide fumarate (TAF) or entecavir, 2. HBsAg ≥ 100 IU/mL but \< or = 3,000 IU/mL at screening, 3. Male and female subjects aged 18 to 70 years (inclusive) at the day of screening, 4. Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 6 months of screening date with no evidence of hepatocellular carcinoma (HCC), 5. No evidence of advanced fibrosis or cirrhosis at screening: elastography (Fibroscan) value ≤ 9 kPa and ultrasonography without any sign of cirrhosis and platelets ≥ 150x109/L, 6. No evidence of advanced fibrosis or cirrhosis before the onset of NUC therapy, 7. HBV DNA \< 20 IU/mL at screening, 8. ALT levels within the normal range of the local lab (\< ULN) at screening, 9. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of IMP. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation, 10. Women of childbearing potential must agree to use a highly effective method of contraception from screening throughout the study period and for 7 days after the last dose of study drug. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception from screening throughout the study period and for 7 days after the last dose of study drug. 1. Women of childbearing potential are sexually mature women who have not undergone bilateral oophorectomy or hysterectomy; or who have not been postmenopausal (ie, who have not menstruated at all) for at least 1 year. 2. Highly effective methods of contraception not using hormonal contraceptives will be intrauterine device, tubal sterilization, Essure microinsert system; male partner sterilization; or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the subject. Note: The double-barrier method (eg, synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide only are not acceptable as highly effective methods of contraception. 11. Screening Electrocardiogram (ECG) without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females, 12. Must be willing and able to comply with all study requirements, 13. Must have the ability to understand and sign a written informed consent form (ICF), 14. Participant covered by Health Insurance (when requested by local regulations) Exclusion Criteria: 1. Any history of decompensation of liver disease including history of ascites, encephalopathy and gastrointestinal bleeding, 2. Any sign of oesophageal and/or gastric varices, 3. Laboratory parameters not within defined thresholds: 1. White blood cells \< 4,000 cells/μL (\< 4.0×109/L); 2. Hemoglobin \< 11 g/dL (\< 110 g/L) for females, \< 13 g/dL (\< 130 g/L) for males; 3. Platelets \< 130,000 per μL (\< 130×109/L); 4. Albumin \< 3.5 g/dL (\< 35 g/L); 5. International normalized ratio (INR) \> 1.5; 6. Total bilirubin \> 1.2 mg/dL (\> 20.52 μmol/L). Note: subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. 7. Alpha-fetoprotein (AFP) \> 20 ng/mL; 8. Creatinine clearance (using the Cockcroft-Gault method) \< 60 mL/min; 4. Co-infection with hepatitis C virus (HCV) (antibodies anti-HCV positive), human immunodeficiency virus type 1 (HIV-1) (antibodies anti-HIV positive) or hepatitis D virus (HDV) (antibodies anti-HDV positive), 5. Evidence or history or suspicion of hepatocellular carcinoma, 6. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Note: subjects under evaluation for possible malignancy are not eligible. 7. Significant cardiovascular, pulmonary, or neurological disease, 8. Received solid organ or bone marrow transplant, 9. Received within 3 months of screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids, anti-TNF) or biologics (eg, monoclonal antibody, IFN), 10. Subjects currently taking medication(s) that are transported through organic anion transporting polypeptide 1 (OATP1) including, but not limited to: atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir, 11. Concomitant treatment with the following medications (if taken within 21 days prior the baseline visit through the end of treatment plus 7 days)/diet: 1. Hematologic stimulating agents (eg, erythropoiesis-stimulating agents; granulocyte colony stimulating factor \[GCSF\]; and thrombopoietin \[TPO\] mimetics), 2. Potent CYP3A4 inhibitors or inducers, including but not limited to antifungals (fluconazole, ketoconazole…), antibiotics (telithromycin, rifabutin, rifampicin…), St. John's Wort, grapefruit juice, anticonvulsants (carbamazepine, phenobarbital, phenytoin…) etc, 3. Immunosuppressant (except short term use of prednisone as a steroid burst \[≤ 1 week of use\]) and cytotoxic medications, 12. Known hypersensitivity or resistance to study drugs or formulation excipients, 13. Diagnosis of autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis, sarcoidosis, psoriasis of greater than mild severity, autoimmune uveitis), poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or immunosuppressed patients, 14. Use of another investigational agent within 6 months of screening and during the whole duration of the trial, 15. Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance, 16. Females who are breastfeeding, pregnant or may wish to become pregnant during the study, 17. Female subjects unwilling to refrain from egg donation and in vitro fertilization during and until at least 7 days after the last study drug dose. Male subjects unwilling to refrain from sperm donation during and until at least 7 days after the last study drug, 18. Any medical condition that, in the opinion of the investigator, could interfere with evaluation of the study objectives or safety of the subjects.