- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04225715
A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (Piranga)
April 10, 2024 updated by: Hoffmann-La Roche
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.
Study Overview
Status
Active, not recruiting
Conditions
Study Type
Interventional
Enrollment (Actual)
280
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Reference Study ID: WV41073 https://forpatients.roche.com/
- Phone Number: 888-662-6728 (U.S and Canada)
- Email: global-roche-genentech-trials@gene.com
Study Locations
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Sofia, Bulgaria, 1431
- University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology
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Sofia, Bulgaria, 1407
- Tokuda Hospital Sofia; Hematology department
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Stara Zagora, Bulgaria, 6000
- Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
- University of Calgary; HSC- Faculty of Medicine
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Edmonton, Alberta, Canada, T6G 2S2
- Uni of Alberta Hospital
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- Ottawa Hospital
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Toronto, Ontario, Canada, M6H 3M1
- Toronto Liver Centre
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Toronto, Ontario, Canada, M5G 2N2
- Toronto General Hospital
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La Serena, Chile, 1700000
- Hospital San Juan de Dios La Serena
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Beijing, China, 100044
- Peking University People's Hospital
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Beijing, China, 100050
- Beijing Friendship Hospital
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Changchun City, China, 130021
- the First Hospital of Jilin University
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Chengdu, China, 610041
- West China Hospital, Sichuan University
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Guangzhou, China, 510515
- Nanfang Hospital, Southern Medical University
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Hangzhou City, China, 310003
- Capital Medical University (CMU) - Beijing Ditan Hospital; Liver Center (Center for Liver Diseases)
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Shanghai City, China, 200040
- Huashan Hospital, Fudan University
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Shanghai City, China, 200025
- Ruijin Hospital Shanghai Jiaotong University School of Medicine
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Clichy, France, 92118
- Hopital Beaujon; Chir 2
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Lyon, France, 69004
- Hopital de la Croix-Rousse ? Groupement Hospitalier Nord; Pharmacie / Secteur Essais Cliniques
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Vandoeuvre-les-nancy, France, 54511
- Hopital Brabois Adultes; Service Médecine Interne Hématologie
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Hong Kong, Hong Kong, 999077
- Queen Mary Hospital
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Shatin, New Territories, Hong Kong
- Prince of Wales Hospital
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Busan, Korea, Republic of, 602-739
- Pusan National University Hospital
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Busan, Korea, Republic of, 614-735
- Inje University Busan Paik Hospital; Clinical Trial Center
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Gangwon-Do, Korea, Republic of, 200-704
- Chuncheon Sacred Heart Hospital
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Seoul, Korea, Republic of, 156-707
- SMG-SNU Boramae Medical Center
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Seoul, Korea, Republic of, 120-752
- Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
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Seoul, Korea, Republic of, 138-736
- Asan Medical Center / Clinical Trial Center
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Seoul, Korea, Republic of
- Seoul National University College of Medicine, Liver Research Institute
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Auckland, New Zealand
- Middlemore Clinical Trials
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Auckland, New Zealand, 1010
- Auckland Clinical Studies Limited
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Cluj-Napoca, Romania, 400006
- Spitalul Clinic Judetean de Urgenta Cluj Napoca
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Barcelona, Spain, 08035
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona
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Pontevedra, Spain, 36071
- Hospital Montecelo
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Madrid
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Majadahonda, Madrid, Spain, 28222
- Hospital Universitario Puerta de Hierro
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Pontevedra
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Vigo, Pontevedra, Spain, 36212
- Hospital Alvaro Cunqueiro; Servicio de Farmacia. Planta -1
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Chang Hua, Taiwan, 500
- Changhua Christian Hospital
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Kaohsiung City, Taiwan, 807
- Kaohsiung Medical University Chung-Ho Memorial Hospital; Pharmacy
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Taichung, Taiwan, 40705
- Taichung Veterans General Hospital
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Taichung, Taiwan, 40447
- China Medical University Hospital; Internal Medicine
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Tainan, Taiwan, 00704
- National Cheng Kung Univ Hosp
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Taipei, Taiwan, 10002
- National Taiwan University Hospital
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Bangkok, Thailand, 10330
- King Chulalongkorn Memorial Hospital
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Bangkok, Thailand, 10700
- Siriraj Hospital
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Bangkok, Thailand, 10330
- Hivnat; Thai Red Cross Center
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Chiang Mai, Thailand, 50200
- Maharaj Nakorn Chiang Mai Hospital
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Liverpool, United Kingdom, L7 8XP
- Royal Liverpool University Hospital
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London, United Kingdom, SW17 0QT
- St George's Hospital
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London, United Kingdom, SE5 9RS
- King College Hospital NHS Foundation Trust
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California
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Rialto, California, United States, 92377
- Inland Empire Liver Foundation
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San Francisco, California, United States, 94115
- Quest Clinical Research
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: 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.
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Nucleos(t)ide (NUC) will be administered orally
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
CpAM (RO7049389) will be administered orally
TLR7 (RO7020531) will be administered orally
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
PEG-IFN will be administered subcutaneously
Other Names:
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Experimental: 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.
|
Nucleos(t)ide (NUC) will be administered orally
CpAM (RO7049389) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
TLR7 (RO7020531) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
PD-L1 LNA (RO7191863) will be administered subcutaneously
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Experimental: 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.
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Nucleos(t)ide (NUC) will be administered orally
siRNA (RO7445482) will be administered subcutaneously
PD-L1 LNA (RO7191863) will be administered subcutaneously
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) loss at 24 weeks post-EOT (End Of Treatment)
Time Frame: Up to 72 weeks
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Up to 72 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with HBsAg loss
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with HBsAg seroconversion
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with Hepatitis B Early Antigen (HBeAg) loss (baseline HBeAg-positive participants).
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with HBeAg seroconversion (baseline HBeAgpositive participants)
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with HBV DNA < lower limit of quantification (LLOQ), <200 IU/mL and <2,000 IU/mL
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBcrAg, HBV RNA, and HBV DNA levels over time (IU/mL)
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Plasma Pharmacokinetics (PK) (TLR7) (IU/mL)
Time Frame: Up to 48 weeks
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Up to 48 weeks
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Plasma PK (CpAM) (IU/mL)
Time Frame: Up to 48 weeks
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Up to 48 weeks
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Plasma PK (NUC) (IU/mL)
Time Frame: Up to 48 weeks
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Up to 48 weeks
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Plasma PK (siRNA) (IU/mL)
Time Frame: Up to 48 weeks
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Up to 48 weeks
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Serum PK (PEG-IFN) (IU/mL)
Time Frame: Up to 48 weeks
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Up to 48 weeks
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Percentage of Participants with Anti-siRNA Antibodies
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Percentage of Participants with Anti-PEG-IFN Antibodies
Time Frame: Up to 96 weeks
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Up to 96 weeks
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Plasma PK PD-L1 LNA
Time Frame: Up to 37 weeks
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Up to 37 weeks
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Percentage of Participants with Anti PD-L1 LNA Antibodies
Time Frame: Up to 85 weeks
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Up to 85 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 5, 2020
Primary Completion (Estimated)
August 15, 2024
Study Completion (Estimated)
January 31, 2025
Study Registration Dates
First Submitted
January 8, 2020
First Submitted That Met QC Criteria
January 9, 2020
First Posted (Actual)
January 13, 2020
Study Record Updates
Last Update Posted (Actual)
April 11, 2024
Last Update Submitted That Met QC Criteria
April 10, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Disease Attributes
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Chronic Disease
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Anti-Infective Agents
- Antiviral Agents
- Peginterferon alfa-2a
Other Study ID Numbers
- WV41073
- 2019-002086-35 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org).
Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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