A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B

NCT ID: NCT04225715

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 281 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-05
• Study Completion Date: 2024-07-19

Brief Summary

This is a study designed to evaluate the safety, tolerability and efficacy of New Molecular Entity (NME) combination therapies in Chronic Hepatitis B (CHB) participants with preserved liver function and without significant fibrosis/cirrhosis. The platform design allows comparison of multiple NME combination therapies against a common control, and introduction of additional treatment arms at later study time points. Each arm will consist of a screening phase (up to 8 weeks), treatment phase (up to 48 weeks) and post-treatment follow-up phase (48 weeks). The safety and efficacy will be monitored throughout the study.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nucleos(t)ide (NUC) Control Arm

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.

Group Type: ACTIVE_COMPARATOR

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

CpAM (RO7049389)

Intervention Type: DRUG

CpAM (RO7049389) will be administered orally

TLR7 (RO7020531)

Intervention Type: DRUG

TLR7 (RO7020531) will be administered orally

Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

siRNA (RO7445482) (Dose 2) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

PEG-IFN

Intervention Type: DRUG

PEG-IFN will be administered subcutaneously

siRNA (RO7445482) + CpAM (RO7049389) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

CpAM (RO7049389)

Intervention Type: DRUG

CpAM (RO7049389) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

siRNA (RO7445482) + TLR7 (RO7020531) + NUC

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

TLR7 (RO7020531)

Intervention Type: DRUG

TLR7 (RO7020531) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

PD-L1 LNA (RO7191863)

Intervention Type: DRUG

PD-L1 LNA (RO7191863) will be administered subcutaneously

siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]

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.

Group Type: EXPERIMENTAL

Nucleos(t)ide (NUC)

Intervention Type: DRUG

Nucleos(t)ide (NUC) will be administered orally

siRNA (RO7445482)

Intervention Type: DRUG

siRNA (RO7445482) will be administered subcutaneously

PD-L1 LNA (RO7191863)

Intervention Type: DRUG

PD-L1 LNA (RO7191863) will be administered subcutaneously

Interventions

Nucleos(t)ide (NUC)

Nucleos(t)ide (NUC) will be administered orally

Intervention Type: DRUG

CpAM (RO7049389)

CpAM (RO7049389) will be administered orally

Intervention Type: DRUG

TLR7 (RO7020531)

TLR7 (RO7020531) will be administered orally

Intervention Type: DRUG

siRNA (RO7445482)

siRNA (RO7445482) will be administered subcutaneously

Intervention Type: DRUG

PEG-IFN

PEG-IFN will be administered subcutaneously

Intervention Type: DRUG

PD-L1 LNA (RO7191863)

PD-L1 LNA (RO7191863) will be administered subcutaneously

Intervention Type: DRUG

Other Intervention Names

Linvencorvir; RG7907; Ruzotolimod; RG7854; Xalnesiran; RG6346; Pegasys®; Cadapersen; RG6084

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Tokuda Hospital Sofia

Sofia, , Bulgaria

University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD

Sofia, , Bulgaria

University of Calgary

Calgary, Alberta, Canada

Uni of Alberta Hospital

Edmonton, Alberta, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Hospital San Juan de Dios La Serena

La Serena, , Chile

Beijing Friendship Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

West China Hospital, Sichuan University

Chengdu, , China

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Ruijin Hospital Shanghai Jiaotong University School of Medicine

Shanghai, , China

Huashan Hospital, Fudan University

Shanghai, , China

Hopital Beaujon

Clichy, , France

Queen Mary Hospital

Hong Kong, , Hong Kong

Auckland Clinical Studies Limited

Auckland, , New Zealand

Middlemore Clinical Trials

Auckland, , New Zealand

Spitalul Clinic Judetean de Urgenta Cluj Napoca

Cluj-Napoca, , Romania

Chuncheon Sacred Heart Hospital

Gangwon-Do, , South Korea

Asan Medical Center / Clinical Trial Center

Seoul, , South Korea

SMG-SNU Boramae Medical Center

Seoul, , South Korea

Seoul National University College of Medicine, Liver Research Institute

Seoul, , South Korea

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Changhua Christian Hospital

Chang-hua, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung Univ Hosp

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

HIVNAT

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

King College Hospital NHS Foundation Trust

London, , United Kingdom

Countries

Bulgaria; Canada; Chile; China; France; Hong Kong; New Zealand; Romania; South Korea; Spain; Taiwan; Thailand; United Kingdom

References

Hou J, Zhang W, Xie Q, Hua R, Tang H, Morano Amado LE, Yang SS, Peng CY, Su WW, Chuang WL, Kim DJ, Avihingsanon A, Kao JH, Leerapun A, Yuen MF, Asselah T, Liang X, Bo Q, Canducci F, Catanese MT, Chen E, Cheng C, Chughlay F, Das S, Glavini K, Guerreiro N, Huang Y, Kakrana P, Kazma R, Patil A, Pavlovic V, Surujbally B, Triyatni M, Upmanyu R, Wat C, Gane E; Piranga Study Group. Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B. N Engl J Med. 2024 Dec 5;391(22):2098-2109. doi: 10.1056/NEJMoa2405485.

Reference Type: DERIVED

PMID: 39774313 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002086-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WV41073

Identifier Type: -

Identifier Source: org_study_id