Hepatitis B, ChronicPhase 2PirangaNCT04225715
A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
A Phase 2 study testing Nucleos(t)ide (NUC), CpAM (RO7049389) and TLR7 (RO7020531) in people with Hepatitis B, Chronic, run by Hoffmann-La Roche at 33 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Nucleos(t)ide (NUC), CpAM (RO7049389) and TLR7 (RO7020531)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 281 participants
- Where
- 33 sitesin 13 countries
- Study dates
- 5 Jul 2020to 19 Jul 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
33 sites in 13 countries.
33 sites in 13 countries
China6 sites
Beijing Friendship Hospital
Beijing, 100050
The First Hospital of Jilin University
Changchun, 130021
West China Hospital, Sichuan University
Chengdu, 610041
Nanfang Hospital, Southern Medical University
Guangzhou, 510515
Ruijin Hospital Shanghai Jiaotong University School of Medicine
Shanghai, 200025
Huashan Hospital, Fudan University
Shanghai, 200040
Taiwan6 sites
Changhua Christian Hospital
Chang-hua, 500
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
National Cheng Kung Univ Hosp
Tainan, 00704
National Taiwan University Hospital
Taipei, 10002
South Korea4 sites
Chuncheon Sacred Heart Hospital
Gangwon-Do, 200-704
Asan Medical Center / Clinical Trial Center
Seoul, 138-736
SMG-SNU Boramae Medical Center
Seoul, 156-707
Seoul National University College of Medicine, Liver Research Institute
Seoul
Canada3 sites
University of Calgary
Calgary, Alberta, T2N 2T9
Uni of Alberta Hospital
Edmonton, Alberta, T6G 2S2
Toronto Liver Centre
Toronto, Ontario, M6H 3M1
Thailand3 sites
HIVNAT
Bangkok, 10330
Siriraj Hospital
Bangkok, 10700
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
Bulgaria2 sites
Tokuda Hospital Sofia
Sofia, 1407
University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD
Sofia, 1431
New Zealand2 sites
Auckland Clinical Studies Limited
Auckland, 1010
Middlemore Clinical Trials
Auckland
Spain2 sites
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035
Hospital Alvaro Cunqueiro
Vigo, Pontevedra, 36212
Romania1 site
Spitalul Clinic Judetean de Urgenta Cluj Napoca
Cluj-Napoca, 400006
United Kingdom1 site
King College Hospital NHS Foundation Trust
London, SE5 9RS
About this study
Official title: A Phase II, Randomised, Adaptive, Open-Label Platform Trial To Evaluate Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
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
- Being tested
- Nucleos(t)ide (NUC), CpAM (RO7049389), TLR7 (RO7020531), siRNA (RO7445482), PEG-IFN
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nucleos(t)ide (NUC)Drug
Nucleos(t)ide (NUC) will be administered orally
CpAM (RO7049389)Drug
Also called Linvencorvir, RG7907
CpAM (RO7049389) will be administered orally
TLR7 (RO7020531)Drug
Also called Ruzotolimod, RG7854
TLR7 (RO7020531) will be administered orally
siRNA (RO7445482)Drug
Also called Xalnesiran, RG6346
siRNA (RO7445482) will be administered subcutaneously
PEG-IFNDrug
Also called Pegasys®
PEG-IFN will be administered subcutaneously
PD-L1 LNA (RO7191863)Drug
Also called Cadapersen, RG6084
PD-L1 LNA (RO7191863) will be administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Nucleos(t)ide (NUC); Drug: siRNA (RO7445482); Drug: PD-L1 LNA (RO7191863) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Follow-up Week (FUW) 24
Secondary outcomes (19)
Percentage of Participants With HBsAg Loss
HBsAg loss was defined as quantitative HBsAg <0.05 IU/mL. The percentage of participants with HBsAg loss was calculated as number of participants with HBsAg loss / total number of participants *100. 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.
Measured: 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
HBsAg seroconversion was defined as a quantitative HBsAg < 0.05 IU/mL and a positive anti-HBs antibody (defined as per assay reactive threshold anti-HBs ≥10 IU/L). 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.
Measured: 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
HBeAg loss was defined as negative /non-reactive HBeAg level. Percentages have been rounded off.
Measured: Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants
HBeAg seroconversion was defined as a negative /non-reactive HBeAg level and a positive anti-HBe antibody. Percentages have been rounded off.
Measured: 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
Chronic HBV infection is characterized by high levels of circulating HBV DNA. Therefore, HBV levels are indicative of virological response. At screening participants were on NUC therapy and had circulating HBV DNA levels below the assay LLOQ or below 20 IU/mL for at least 6 months. The emergence of a virological breakthrough (HBV DNA >100 IU/mL or >1 log increase from nadir) while on NUC therapy, or the emergence of a virological relapse (>2,000 IU/mL) in participants taken off NME combination and NUC therapy during follow-up, was monitored through the quantification of HBV DNA in plasma.
Measured: FUW 12, 24, 36, and 48
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time
The serological markers of HBV infection include viral antigens (HBsAg \& HBeAg) and antibody (anti-HBs). Changes in serological markers and efficacy biomarkers (HBV RNA) from baseline are reported. Change from baseline for HBV DNA was assessed in 'ON NUC' participants.
Measured: HBsAg, Anti-HBs, HBeAg & HBV RNA: Combo 1 to 6 and NUC arm: Weeks 24, 36, 48, FUW 24 and FUW 48; Combo 7: Week 24, FUW 24 & FUW 48; Combo 8: Weeks 24, 36, FUW 24 & FUW 48; HBV DNA: FUW 24 and FUW 48
Combos 7 and 8: Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Week 1 (AUC1-0-168h) of PD-L1 LNA
The AUC was predicted and summarized by modelling \& simulation via the population pharmacokinetics (PopPK) method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.
Measured: Predose on Day 1 and up to 168 hours post dose (Week 1)
Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA
The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.
Measured: Predose on Day 1 and up to 168 hours post dose (Week 1)
Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA
The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.
Measured: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)
Combos 7 and 8: Cmax at Week 12 (Cmax12-0-168h) of PD-L1 LNA
The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.
Measured: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve (AUC) Over Days 1-28 of siRNA
The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.
Measured: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 1-28 of siRNA
The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.
Measured: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve During the Dosing Interval (AUC Tau) Over Days 29-56 of siRNA
The AUC tau was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. Simulations for the dosing interval between Day 29 and Day 56 was done using population PK modeling informed by sparse PK samples collected on Days 1, 85, 169, 253, and 337 at predose, 1-3 hours, and 4-6 hours post dose.
Measured: From Day 29 up to Day 56
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 29-56 of siRNA
The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. Simulations for the dosing interval between Day 29 and Day 56 was done using population PK modeling informed by sparse PK samples collected on Days 1, 85, 169, 253, and 337 at predose, 1-3 hours, and 4-6 hours post dose.
Measured: From Day 29 up to Day 56
Combos 1 and 6: AUC of TLR7
The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.
Measured: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36
Combos 1 and 6: Cmax of TLR7
The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.
Measured: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Measured: From Day 1 up to end of 48 weeks of follow up (up to approximately 1.8 years)
Combos 2, 3, 4, 5, 6, 7 and 8: Number of Participants With Anti-siRNA Antibodies
Treatment-emergent anti drug antibody (ADA) was defined as participants who seroconverted or experienced a boost in preexisting ADA during the study. Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples were greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).
Measured: From Day 1 up to end of follow up (up to approximately 4 years)
Combos 7 and 8: Number of Participants With Anti-PD-L1 Antibodies
Treatment-emergent ADA was defined as participants who seroconverted or experienced a boost in preexisting ADA during the study. Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples were greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).
Measured: From Day 1 for Combo 7 and 8 up to end of follow up (Up to approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start5 Jul 2020
- Primary completion19 Jul 2024
- Study completion19 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 281 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225715
- Sponsor's protocol ID
- WV41073
- Other IDs
- 2019-002086-35, 2019
- Acronym
- Piranga
- Status last verified
- Aug 2025
- First submitted
- 8 Jan 2020
- Last updated
- 19 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
Cheng C, Xie Q, Gane E, Morano Amado LE, Yang SS, Zhang W, Jia J, Asselah T, Kao JH, Peng CY, Su WW, Tanwandee T, Liang X, Catanese MT, Chen E, Chughlay F, Das S, Glavini K, Guerreiro N, Huang Y, Kazma R, Liang Y, McGeown C, Patil A, Upmanyu R, Wat C, Yuen MF, Hou J; Piranga Study Group. Outcomes of nucleos(t)ide analogue discontinuation following finite xalnesiran-based therapies in chronic hepatitis B. JHEP Rep. 2026 Jul 15:101958. doi: 10.1016/j.jhepr.2026.101958. Online ahead of print.
PubMed 42456805Hou 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.
PubMed 39774313
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomised, Adaptive, Open-Label Platform Trial To Evaluate Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT04225715
- Acronym / sponsor ID
- Piranga / WV41073
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 281 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 5 Jul 2020 (actual)
- Primary completion
- 19 Jul 2024 (actual)
- Study completion
- 19 Jul 2024 (actual)
- First posted
- 13 Jan 2020 (actual)
- Results
- Posted 19 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Nucleos(t)ide (NUC) Control Arm | Active comparator | Drug: Nucleos(t)ide (NUC)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. |
| Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: CpAM (RO7049389), Drug: TLR7 (RO7020531)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. |
| Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: siRNA (RO7445482)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. |
| siRNA (RO7445482) (Dose 2) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: siRNA (RO7445482)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. |
| siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: siRNA (RO7445482), Drug: PEG-IFNParticipants 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. |
| siRNA (RO7445482) + CpAM (RO7049389) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: CpAM (RO7049389), Drug: siRNA (RO7445482)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. |
| siRNA (RO7445482) + TLR7 (RO7020531) + NUC | Experimental | Drug: Nucleos(t)ide (NUC), Drug: TLR7 (RO7020531), Drug: siRNA (RO7445482)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. |
| siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1] | Experimental | Drug: Nucleos(t)ide (NUC), Drug: siRNA (RO7445482), Drug: PD-L1 LNA (RO7191863)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. |
| siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2] | Experimental | Drug: Nucleos(t)ide (NUC), Drug: siRNA (RO7445482), Drug: PD-L1 LNA (RO7191863)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nucleos(t)ide (NUC)Nucleos(t)ide (NUC) will be administered orally | Drug | 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)Also: Linvencorvir, RG7907CpAM (RO7049389) will be administered orally | Drug | Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC, siRNA (RO7445482) + CpAM (RO7049389) + NUC |
| TLR7 (RO7020531)Also: Ruzotolimod, RG7854TLR7 (RO7020531) will be administered orally | Drug | Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC, siRNA (RO7445482) + TLR7 (RO7020531) + NUC |
| siRNA (RO7445482)Also: Xalnesiran, RG6346siRNA (RO7445482) will be administered subcutaneously | Drug | 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-IFNAlso: Pegasys®PEG-IFN will be administered subcutaneously | Drug | siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC |
| PD-L1 LNA (RO7191863)Also: Cadapersen, RG6084PD-L1 LNA (RO7191863) will be administered subcutaneously | Drug | siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2], siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1] |
Primary outcome
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT)
Time frame: Follow-up Week (FUW) 24
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.
19 secondary outcomes
Percentage of Participants With HBsAg Loss
Time frame: 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
Time frame: 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
Time frame: Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants
Time frame: 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
Time frame: FUW 12, 24, 36, and 48
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time
Time frame: HBsAg, Anti-HBs, HBeAg & HBV RNA: Combo 1 to 6 and NUC arm: Weeks 24, 36, 48, FUW 24 and FUW 48; Combo 7: Week 24, FUW 24 & FUW 48; Combo 8: Weeks 24, 36, FUW 24 & FUW 48; HBV DNA: FUW 24 and FUW 48
Combos 7 and 8: Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Week 1 (AUC1-0-168h) of PD-L1 LNA
Time frame: Predose on Day 1 and up to 168 hours post dose (Week 1)
Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA
Time frame: Predose on Day 1 and up to 168 hours post dose (Week 1)
Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA
Time frame: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)
Combos 7 and 8: Cmax at Week 12 (Cmax12-0-168h) of PD-L1 LNA
Time frame: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve (AUC) Over Days 1-28 of siRNA
Time frame: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 1-28 of siRNA
Time frame: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve During the Dosing Interval (AUC Tau) Over Days 29-56 of siRNA
Time frame: From Day 29 up to Day 56
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 29-56 of siRNA
Time frame: From Day 29 up to Day 56
Combos 1 and 6: AUC of TLR7
Time frame: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36
Combos 1 and 6: Cmax of TLR7
Time frame: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36
Number of Participants With Adverse Events (AEs)
Time frame: From Day 1 up to end of 48 weeks of follow up (up to approximately 1.8 years)
Combos 2, 3, 4, 5, 6, 7 and 8: Number of Participants With Anti-siRNA Antibodies
Time frame: From Day 1 up to end of follow up (up to approximately 4 years)
Combos 7 and 8: Number of Participants With Anti-PD-L1 Antibodies
Time frame: From Day 1 for Combo 7 and 8 up to end of follow up (Up to approximately 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42456805Cheng C, Xie Q, Gane E, Morano Amado LE, Yang SS, Zhang W, Jia J, Asselah T, Kao JH, Peng CY, Su WW, Tanwandee T, Liang X, Catanese MT, Chen E, Chughlay F, Das S, Glavini K, Guerreiro N, Huang Y, Kazma R, Liang Y, McGeown C, Patil A, Upmanyu R, Wat C, Yuen MF, Hou J; Piranga Study Group. Outcomes of nucleos(t)ide analogue discontinuation following finite xalnesiran-based therapies in chronic hepatitis B. JHEP Rep. 2026 Jul 15:101958. doi: 10.1016/j.jhepr.2026.101958. Online ahead of print.
- Derived from this study: PubMed 39774313Hou 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.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
33 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nucleos(t)ide (NUC), CpAM (RO7049389) and TLR7 (RO7020531) in people with Hepatitis B, Chronic, run by Hoffmann-La Roche at 33 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in China, Taiwan, South Korea, Canada, Thailand and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) (time frame: Follow-up Week (FUW) 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04225715, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.