chronic disease viral infection
Conditions
Interventions
Screening
* Physical examination
* Vital Signs
* Electrocardiogram (ECG)
* Abdominal ultrasound scan
* Liver elastography
* Blood collection
* Urine samples
* Breath test: A breath test to test for al
Sponsors
Covance
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Informed Consent 1. Able and willing to provide written informed consent and to comply with the study protocol according to International Council for Harmonization (ICH) and local regulations. Age 2. Participants must be between 18 and 65 years of age, inclusive, at the time of signing the informed consent. Weight 3. Body mass index between 18 and 32 kg/m2 inclusive. Type of Participants and Disease Characteristics 4. Participants with CHB infection (HBsAg positive for **6 months) who are on NUC (entecavir or tenofovir alafenamide/disoproxil fumarate) monotherapy for *12 months, having received the same NUC therapy for** 3 months prior to screening. 5. HBV DNA below the LLOQ or 6 months prior to screening and confirmed at screening. 6. Alanine transaminase (ALT) **1.5 x upper limit of normal (ULN) for > 6 months prior to screening, and confirmed at screening 7. Screening laboratory values (hematology, chemistry, urinalysis) within normal range, or judged not clinically significant by the Investigator and Medical Monitor. Sex 8. Male and female participants: The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. The reliability of sexual abstinence for enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing fetal/embryonic drug exposure. The following contraception requirements must be followed unless otherwise stated in the respective appendix of each treatment arm. a) Female Participants: A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies: * Woman of non-childbearing potential (WONCBP), as defined in Appendix 5. * Woman of childbearing potential (WOCBP), who: * Agrees to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the final dose of study treatment. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal occlusion, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices (see Appendix 5). * Has a negative pregnancy test at screening (Day -14 to -7). In addition, WOCBP must be willing to undergo a urine pregnancy test every 3 months until the end of study. b) Male Participants: During the treatment period and for at least 6 months after the final dose of study treatment, agree to: * Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of <1% per year, with a partner who is a woman of childbearing potential (WOCBP, as defined in Section 1 in Appendix 5). * With pregnant female partner, remain abstinent (refrain from heterosexual intercourse) or use contraceptive
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Pregnant (positive pregnancy test) or lactating women. 2. Co-infection with other pathogens such as hepatitis A (HAV), hepatitis C (HCV), hepatitis D (HDV), hepatitis E (HEV), or human immunodeficiency virus (HIV). 3. History of cirrhosis or current evidence of significant liver fibrosis or cirrhosis (F3 or above on liver biopsy, *7.4 kPa on transient elastography, >1.32 m/s on acoustic radiation force impulse [ARFI] elastography, or >3.13 kPa on magnetic resonance [MR] elastography), or decompensated liver disease (e.g., ascites, hepatic encephalopathy). Liver biopsy or transient elastography/ARFI/MR result must be obtained within 6 months prior to randomization. 4. History of or suspicion of hepatocellular carcinoma (HCC) (e.g, elevated *- fetoprotein [AFP] levels, suggestive lesions on abdominal ultrasound or other imaging, etc.). 5. Thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], free thyroxin [FT4]) at screening, as judged by the Investigator and Medical Monitor. 6. Clinically significant disease other than CHB that, in the opinion of the Investigator, makes the participant unsuitable for the study. 7. Pre-existing cardiac disease that in the opinion of the investigator would increase the risk for the patient to participate to the study. 8. History of alcohol abuse and/or drug abuse within one year of randomization. 9. History of having received (in the last 6 months) or currently receiving any systemic antineoplastic (including radiation) or immunosuppressive (including biologic immunosuppressors) or immune modulating treatment (including non-biological oral immune modulating drugs; e.g., methotrexate > 25 mg per week, azathioprine > 3.0 mg/kg/day or 6-mercaptopurine > 1.5 mg/kg/day) for malignant or non-malignant disorders. 10. Currently taking, or have received within 3 months of Day 1, systemic corticosteroids at a high-dose (e.g., 40 mg prednisolone per day for) > 7 days, or a low-dose (e.g., 20 mg prednisolone per day) for > 14 days. Diagnostic Assessments 11. Electrocardiogram (ECG) with clinically significant abnormalities, including QTcF interval (QT corrected using Fridericia*s formula) *450 msec for males and *470 msec for females at screening. 12. Laboratory parameters at screening: a) Hemoglobin 1.1. b) Albumin ULN (exception: Gilbert*s disease). c) Positive results for anti-mitochondrial antibodies (AMA >1:80), antinuclear antibody (ANA >1:80), anti*smooth muscle antibody (ASMA >1:40), or antithyroperoxidase antibodies (a-TPO >10). d) White blood cell count <2500 cells/mm3; neutrophil count <1500 cells/mm3 (<1000 cells/mm3 if considered a physiological variant in a participant of African descent). e) Glomerular filtration rate (GFR; using Modification of Diet in Renal Disease [MDRD]) * 60 mL/min. f) Positive test for drugs of abuse (including recreational drugs) and/or positive alcohol test at screening. For positive cannabinoids test, the eligibility is at the Investigator*s discretion. Prior/Concurrent Clinical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint * % participants with HBsAg loss at 24 weeks post-EOT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint * % participants with HBsAg loss * % participants with HBsAg seroconversion. * % participants with HBeAg loss (baseline HBeAg-positive participants). * % participants with HBeAg seroconversion (baseline HBeAg-positive participants). * % participants with HBV DNA | — |
Countries
Netherlands
Outcome results
None listed