PD-L1 LNA (RO7191863) for Chronic Hepatitis B

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Chronic Hepatitis BPD-L1 LNA (RO7191863) - Drug
Eligibility
18 - 65
All Sexes
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Study Summary

This trial will test the safety and effectiveness of new hepatitis B treatments in people with mild liver damage. It will compare different combinations of drugs against each other and a control group.

Eligible Conditions
  • Chronic Hepatitis B

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

1 Primary · 16 Secondary · Reporting Duration: Up to 96 weeks

Up to 37 weeks
Plasma PK PD-L1 LNA
Up to 48 weeks
Plasma PK (CpAM) (IU/mL)
Plasma PK (NUC) (IU/mL)
Plasma PK (siRNA) (IU/mL)
Plasma Pharmacokinetics (PK) (TLR7) (IU/mL)
Serum PK (PEG-IFN) (IU/mL)
Up to 72 weeks
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) loss at 24 weeks post-EOT (End Of Treatment)
Up to 85 weeks
Percentage of Participants with Anti PD-L1 LNA Antibodies
Up to 96 weeks
Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBcrAg, HBV RNA, and HBV DNA levels over time (IU/mL)
Percentage of Participants with Adverse Events (AEs)
Percentage of Participants with Anti-PEG-IFN Antibodies
Percentage of Participants with Anti-siRNA Antibodies
Percentage of Participants with HBV DNA < lower limit of quantification (LLOQ), <200 IU/mL and <2,000 IU/mL
Percentage of Participants with HBeAg seroconversion (baseline HBeAgpositive participants)
Percentage of Participants with HBsAg loss
Percentage of Participants with HBsAg seroconversion
Percentage of Participants with Hepatitis B Early Antigen (HBeAg) loss (baseline HBeAg-positive participants).

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

14 Treatment Groups

Nucleos(t)ide (NUC) Control Arm
1 of 14
Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7...
1 of 14
siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO71...
1 of 14
Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC
1 of 14
siRNA (RO7445482) (Dose 2) + NUC
1 of 14
siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC
1 of 14
siRNA (RO7445482) + NUC [2]
1 of 14
CpAM (RO7049389) + TLR7 (RO7020531) + NUC
1 of 14
siRNA (RO7445482) + NUC [1]
1 of 14
siRNA (RO7445482) + PEG-IFN + NUC
1 of 14
siRNA (RO7445482) + CpAM (RO7049389) + NUC
1 of 14
siRNA (RO7445482) + TLR7 (RO7020531) + NUC
1 of 14
siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [1]
1 of 14
siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]
1 of 14

Active Control

Experimental Treatment

275 Total Participants · 14 Treatment Groups

Primary Treatment: PD-L1 LNA (RO7191863) · No Placebo Group · Phase 2

Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), TLR7 (RO7020531), CpAM (RO7049389) · Intervention Types: Drug, Drug, Drug
siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1]Experimental Group · 3 Interventions: PD-L1 LNA (RO7191863), Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUCExperimental Group · 2 Interventions: Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug
siRNA (RO7445482) (Dose 2) + NUCExperimental Group · 2 Interventions: Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug
siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), PEG-IFN, siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + NUC [2]Experimental Group · 2 Interventions: Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug
CpAM (RO7049389) + TLR7 (RO7020531) + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), TLR7 (RO7020531), CpAM (RO7049389) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + NUC [1]Experimental Group · 2 Interventions: Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug
siRNA (RO7445482) + PEG-IFN + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), PEG-IFN, siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + CpAM (RO7049389) + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), CpAM (RO7049389), siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + TLR7 (RO7020531) + NUCExperimental Group · 3 Interventions: Nucleos(t)ide (NUC), TLR7 (RO7020531), siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [1]Experimental Group · 3 Interventions: PD-L1 LNA (RO7191863), Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2]Experimental Group · 3 Interventions: PD-L1 LNA (RO7191863), Nucleos(t)ide (NUC), siRNA (RO7445482) · Intervention Types: Drug, Drug, Drug
Nucleos(t)ide (NUC) Control Arm
Drug
ActiveComparator Group · 1 Intervention: Nucleos(t)ide (NUC) · Intervention Types: Drug

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: up to 96 weeks

Who is running the clinical trial?

Hoffmann-La RocheLead Sponsor
2,361 Previous Clinical Trials
1,067,808 Total Patients Enrolled
Clinical TrialsStudy DirectorHoffmann-La Roche
2,148 Previous Clinical Trials
875,898 Total Patients Enrolled

Eligibility Criteria

Age 18 - 65 · All Participants · 6 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
People with chronic hepatitis B who have been on entecavir or tenofovir alafenamide/disoproxil fumarate monotherapy for at least 12 months and have been taking the same therapy for at least three months prior to screening are eligible for the study.
Women who are not pregnant, who are not breastfeeding, and who agree to remain abstinent or use highly effective contraceptive methods are eligible to participate.
Male participants must agree to remain abstinent from heterosexual intercourse, use contraceptive measures, and refrain from donating sperm during the treatment period and for at least 6 months after the final dose of study treatment.
Alanine transaminase (ALT) is within normal limits (1.5 x ULN or lower) for more than six months prior to screening and is confirmed at screening.
People with a body mass index between 18 and 32 kg/m2 inclusive are considered to be of a healthy weight.
The person has had a negative Hepatitis B virus (HBV) DNA test for at least 6 months before screening.