Phase 2
N=281
A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
Hepatitis B, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT04225715 ↗Enrolled (actual)
281
Serious AEs
5.4%
Results posted
Sep 2025
Primary outcome: Primary: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) — 0; 0; 6.7; 3.3 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Nucleos(t)ide (NUC) (Drug); CpAM (RO7049389) (Drug); TLR7 (RO7020531) (Drug); siRNA (RO7445482) (Drug); PEG-IFN (Drug); PD-L1 LNA (RO7191863) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) |
0; 0; 6.7; 3.3; 23.3; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Loss |
0; 0; 6.1; 0; 0; 13.3 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants |
0; 0; 22.2; 50; 33.3; 28.6 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants |
0; 0; 11.1; 0; 8.3; 14.3 | — |
| SECONDARY Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL |
0; 3; 4; 4; 7; 2 | — |
| SECONDARY Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time |
-0.08; -0.11; -1.49; -1.78; -1.89; -1.38 | — |
| SECONDARY 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 |
1047 | — |
| SECONDARY Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA |
163 | — |
| SECONDARY Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA |
1143 | — |
| SECONDARY Combos 7 and 8: Cmax at Week 12 (Cmax12-0-168h) of PD-L1 LNA |
165 | — |
| SECONDARY Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve (AUC) Over Days 1-28 of siRNA |
4670; 11098; 11073; 9831; 9780; 9110 | — |
| SECONDARY Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 1-28 of siRNA |
190; 463; 450; 408; 373; 311 | — |
| SECONDARY 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 |
5401; 12591; 12623; 11207; 11216; 10513 | — |
| SECONDARY Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 29-56 of siRNA |
192; 468; 454; 411; 376; 315 | — |
| SECONDARY Combos 1 and 6: AUC of TLR7 |
3139; 2813 | — |
| SECONDARY Combos 1 and 6: Cmax of TLR7 |
1548; 1491 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
27; 34; 30; 29; 30; 18 | — |
| SECONDARY Combos 2, 3, 4, 5, 6, 7 and 8: Number of Participants With Anti-siRNA Antibodies |
3; 2; 12; 1; 3; 10 | — |
| SECONDARY Combos 7 and 8: Number of Participants With Anti-PD-L1 Antibodies |
16; 15 | — |
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.
Eligibility Criteria
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 6 months prior to screening and confirmed at screening.
- Alanine transaminase (ALT) 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.
Data sourced from ClinicalTrials.gov (NCT04225715). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.