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

NCT04225715 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: WV410732019-002086-35
• Study Type: interventional
• Target: 281
• Locations: 13 countries
• Sites: 33

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT)

  HBsAg loss was defined as quantitative HBsAg \<0.05 international units/milliliters (IU/mL). The percentage of participants with HBsAg loss was calculated as number of participants with HBsAg loss / total number of participants \*100. 95% confidence interval (CI) was calculated using the Clopper-Pearson method. Percentages have been rounded off.

  Follow-up Week (FUW) 24

Secondary Outcomes (19)

• Percentage of Participants With HBsAg Loss

  Combos 1 and 5: Weeks 24, 36, 48 and FUW 48; Combos 2, 3, 4, 6 and NUC Arm: Week 48 and FUW 48; Combo 7: Week 24; Combo 8: Week 36

• Percentage of Participants With HBsAg Seroconversion

  Combos 1 and 5: Weeks 24, 36, 48, FUW 24 and FUW 48; Combos 2, 3, 4, 6 and NUC Arm: Week 48, FUW 24 and FUW 48; Combo 7: Week 24 and FUW 24; Combo 8: Week 36 and FUW 24

• Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants

  Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48

• Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants

  Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48

• Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL

  FUW 12, 24, 36, and 48

Study Arms (9)

Nucleos(t)ide (NUC) Control Arm

ACTIVE COMPARATOR

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.

Drug: Nucleos(t)ide (NUC)

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

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: CpAM (RO7049389); Drug: TLR7 (RO7020531)

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

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482)

siRNA (RO7445482) (Dose 2) + NUC

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482)

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

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482); Drug: PEG-IFN

siRNA (RO7445482) + CpAM (RO7049389) + NUC

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: CpAM (RO7049389); Drug: siRNA (RO7445482)

siRNA (RO7445482) + TLR7 (RO7020531) + NUC

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: TLR7 (RO7020531); Drug: siRNA (RO7445482)

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

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482); Drug: PD-L1 LNA (RO7191863)

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

EXPERIMENTAL

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.

Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482); Drug: PD-L1 LNA (RO7191863)

Interventions

Nucleos(t)ide (NUC) DRUG

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

Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC; Nucleos(t)ide (NUC) Control Arm; Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC; siRNA (RO7445482) (Dose 2) + NUC; siRNA (RO7445482) + CpAM (RO7049389) + NUC; siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]; siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC; siRNA (RO7445482) + TLR7 (RO7020531) + NUC; siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]

CpAM (RO7049389) DRUG

CpAM (RO7049389) will be administered orally

Also known as: Linvencorvir, RG7907

Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC; siRNA (RO7445482) + CpAM (RO7049389) + NUC

TLR7 (RO7020531) DRUG

TLR7 (RO7020531) will be administered orally

Also known as: Ruzotolimod, RG7854

Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC; siRNA (RO7445482) + TLR7 (RO7020531) + NUC

siRNA (RO7445482) DRUG

siRNA (RO7445482) will be administered subcutaneously

Also known as: Xalnesiran, RG6346

Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC; siRNA (RO7445482) (Dose 2) + NUC; siRNA (RO7445482) + CpAM (RO7049389) + NUC; siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]; siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC; siRNA (RO7445482) + TLR7 (RO7020531) + NUC; siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]

PEG-IFN DRUG

PEG-IFN will be administered subcutaneously

Also known as: Pegasys®

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

PD-L1 LNA (RO7191863) DRUG

PD-L1 LNA (RO7191863) will be administered subcutaneously

Also known as: Cadapersen, RG6084

siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]; siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (33)

Tokuda Hospital Sofia

Sofia, 1407, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Uni of Alberta Hospital

Edmonton, Alberta, T6G 2S2, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Hospital San Juan de Dios La Serena

La Serena, 1700000, Chile

Location

Beijing Friendship Hospital

Beijing, 100050, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Ruijin Hospital Shanghai Jiaotong University School of Medicine

Shanghai, 200025, China

Location

Huashan Hospital, Fudan University

Shanghai, 200040, China

Location

Hopital Beaujon

Clichy, 92118, France

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies Limited

Auckland, 1010, New Zealand

Location

Middlemore Clinical Trials

Auckland, New Zealand

Location

Spitalul Clinic Judetean de Urgenta Cluj Napoca

Cluj-Napoca, 400006, Romania

Location

Chuncheon Sacred Heart Hospital

Gangwon-Do, 200-704, South Korea

Location

Asan Medical Center / Clinical Trial Center

Seoul, 138-736, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 156-707, South Korea

Location

Seoul National University College of Medicine, Liver Research Institute

Seoul, South Korea

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36212, Spain

Location

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

Barcelona, 08035, Spain

Location

Changhua Christian Hospital

Chang-hua, 500, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung Univ Hosp

Tainan, 00704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

HIVNAT

Bangkok, 10330, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

King College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39774313 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

linvencorvir; RO7020531; RNA, Small Interfering; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RNA, Antisense; Antisense Elements (Genetics); Nucleic Acids, Nucleotides, and Nucleosides; RNA; Nucleic Acids; RNA, Small Untranslated; RNA, Untranslated

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 13, 2020
• Study Start: July 5, 2020
• Primary Completion: July 19, 2024
• Study Completion: July 19, 2024
• Last Updated: September 19, 2025
• Results First Posted: September 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); ES (2); NZ (2); CN (6); FR (1); RO (1); TW (6); BU (2); HK (1); TH (3); CL (1); KR (4); CA (3)