The trial is taking place at:
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Quest Clinical Research | San Francisco, CA

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

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Roche

Status and phase

Active, not recruiting
Phase 2

Conditions

Hepatitis B, Chronic

Treatments

Drug: PD-L1 LNA (RO7191863)
Drug: PEG-IFN
Drug: CpAM (RO7049389)
Drug: Nucleos(t)ide (NUC)
Drug: siRNA (RO7445482)
Drug: TLR7 (RO7020531)

Study type

Interventional

Funder types

Industry

Identifiers

NCT04225715
2019-002086-35 (EudraCT Number)
WV41073

Details and patient eligibility

About

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.

Enrollment

280 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

280 participants in 9 patient groups

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

Trial contacts and locations

51

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Central trial contact

Reference Study ID: WV41073 https://forpatients.roche.com/

Data sourced from clinicaltrials.gov

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