A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (Piranga)
Hepatitis B, Chronic
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility Criteria
Inclusion Criteria:
- Body mass index between 18 and 32 kg/m2 inclusive.
- Participants with Chronic Hepatitis B (CHB) infection (HBsAg positive for >=6 months) who are on established NUC (entecavir or tenofovir alafenamide/disoproxil fumarate) monotherapy for >=12 months, having received the same NUC therapy for >=3 months prior to screening.
- HBV DNA below the lower LLOQ or < 20 IU/mL for > 6 months prior to screening and confirmed at screening.
- Alanine transaminase (ALT) <=1.5 x upper limit of normal (ULN) for > 6 months prior to screening and confirmed at screening.
- Female Participants: Eligible to participate if she is not pregnant, not breastfeeding and agrees to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods.
- Male Participants: During the treatment period and for at least 6 months after the final dose of study treatment, agrees to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.
Exclusion Criteria:
- Pregnant or lactating women.
- Co-infection with other pathogens such as Hepatitis A, C, D and E or Human Immunodeficiency Virus (HIV).
- History of cirrhosis or current evidence of significant liver fibrosis or cirrhosis or decompensated liver disease.
- History of or suspicion of Hepatocellular Carcinoma (HCC).
- Thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests.
- Clinically significant disease other than CHB that, in the opinion of the Investigator, makes the participant unsuitable for the study.
- Pre-existing cardiac disease that in the opinion of the investigator would increase the risk for the participant to take part in the study.
- History of alcohol abuse and/or drug abuse within one year of randomization.
- 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.
- Currently taking, or have received within 3 months of Day 1, systemic corticosteroids.
- Electrocardiogram (ECG) with clinically significant abnormalities.
- Previous treatment with an investigational agent for Hepatitis B (HBV) within 6 months prior to screening.
Sites / Locations
- Inland Empire Liver Foundation
- Quest Clinical Research
- Tokuda Hospital Sofia; Hematology department
- University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology
- Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
- University of Calgary; HSC- Faculty of Medicine
- Uni of Alberta Hospital
- Ottawa Hospital
- Toronto General Hospital
- Toronto Liver Centre
- Hospital San Juan de Dios La Serena
- Peking University People's Hospital
- Beijing Friendship Hospital
- The First Hospital of Jilin University
- West China Hospital, Sichuan University
- Nanfang Hospital, Southern Medical University
- Capital Medical University (CMU) - Beijing Ditan Hospital; Liver Center (Center for Liver Diseases)
- Ruijin Hospital Shanghai Jiaotong University School of Medicine
- Huashan Hospital, Fudan University
- Hopital Beaujon; Chir 2
- Hopital de la Croix-Rousse ? Groupement Hospitalier Nord; Pharmacie / Secteur Essais Cliniques
- Hopital Brabois Adultes; Service Médecine Interne Hématologie
- Queen Mary Hospital
- Prince of Wales Hospital
- Pusan National University Hospital
- Inje University Busan Paik Hospital; Clinical Trial Center
- Chuncheon Sacred Heart Hospital
- Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
- Asan Medical Center / Clinical Trial Center
- SMG-SNU Boramae Medical Center
- Seoul National University College of Medicine, Liver Research Institute
- Auckland Clinical Studies Limited
- Middlemore Clinical Trials
- Spitalul Clinic Judetean de Urgenta Cluj Napoca
- Hospital Universitario Puerta de Hierro
- Hospital Alvaro Cunqueiro; Servicio de Farmacia. Planta -1
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona
- Hospital Montecelo
- Changhua Christian Hospital
- Kaohsiung Medical University Chung-Ho Memorial Hospital; Pharmacy
- China Medical University Hospital; Internal Medicine
- Taichung Veterans General Hospital
- National Cheng Kung Univ Hosp
- National Taiwan University Hospital
- Hivnat; Thai Red Cross Center
- King Chulalongkorn Memorial Hospital
- Siriraj Hospital
- Maharaj Nakorn Chiang Mai Hospital
- Royal Liverpool University Hospital
- King College Hospital NHS Foundation Trust
- St George's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Nucleos(t)ide (NUC) Control Arm
Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC
Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC
siRNA (RO7445482) (Dose 2) + NUC
siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC
siRNA (RO7445482) + CpAM (RO7049389) + NUC
siRNA (RO7445482) + TLR7 (RO7020531) + NUC
siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]
siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]
Participants will continue their background NUC therapy for the 48-week treatment period. At the end of the treatment period, in line with current CHB treatment guidelines, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7049389 (600 mg once daily [QD]) in addition to their background NUC therapy for the 48-week treatment period. RO7020531 (150 mg once every other day [QOD]) will be administered during Weeks 1-12 and Weeks 25-36. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 1) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. PEG-IFN will be administered at a dose of 180 μg once weekly (QW) for 48 weeks. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) and RO7049389 (600 mg QD) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. RO7020531 (150 mg QOD) will be administered during Weeks 13-24 and Weeks 37-48 (i.e., 2 treatment cycles of 12 weeks' duration each and 42 doses of RO7020531 for each cycle). At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) during Weeks 1-24 and RO7191863 (Dose 1) will be administered during Weeks 13-24, in addition to their background NUC therapy for the 24-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.
Participants will receive RO7445482 (Dose 2) during Weeks 1-24 and RO7191863 (Dose 1) will be administered during Weeks 25-36, in addition to their background NUC therapy for the 36-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.