Trial · NCT04225715
A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
NCT04225715, Phase 2, Completed, Hoffmann-La Roche; results first posted 2025-09-19
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B. Trials, record NCT04225715. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04225715
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
- NCT number
- NCT04225715
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 281 participants, actual
- Lead sponsor
- Hoffmann-La Roche
- Conditions
- Hepatitis B, Chronic
- Interventions
- Nucleos(t)ide (NUC), CpAM (RO7049389), TLR7 (RO7020531), siRNA (RO7445482), PEG-IFN, PD-L1 LNA (RO7191863)
- First posted
- 2020-01-13
- Last updated
- 2025-09-19
- Other registries' IDs
- eudract:2019-002086-35
- Results first posted
- 2025-09-19
Source ClinicalTrials.gov
Registered outcomes20
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | 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. |
| Secondary | Percentage of Participants With HBsAg Loss | 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 | 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. |
| Secondary | Percentage of Participants With HBsAg Seroconversion | 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 | 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. |
| Secondary | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants | Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48 | HBeAg loss was defined as negative /non-reactive HBeAg level. Percentages have been rounded off. |
| Secondary | Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants | Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48 | HBeAg seroconversion was defined as a negative /non-reactive HBeAg level and a positive anti-HBe antibody. Percentages have been rounded off. |
| 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 | FUW 12, 24, 36, and 48 | 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. |
| Secondary | Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time | 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 | 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. |
| 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 | Predose on Day 1 and up to 168 hours post dose (Week 1) | 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. |
| Secondary | Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA | Predose on Day 1 and up to 168 hours post dose (Week 1) | 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. |
| Secondary | Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA | Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12) | 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. |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 registered outcomesOutcomes20
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Follow-up Week (FUW) 24 | Modified Intent to Treat (mITT) population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. | percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With HBsAg Loss | 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 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. Number analyzed included participants with data available for analysis at that specified timepoint. | percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With HBsAg Seroconversion | 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 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. Number analyzed included participants with data available for analysis at that specified timepoint. | percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants | Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants from the mITT population who were positive for HBeAg at baseline. Number analyzed included participants with data available for analysis at that specified timepoint. | percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants | Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants from the mITT population who were positive for HBeAg at baseline. Number analyzed included participants with data available for analysis at that specified timepoint. | percentage of participants | NUMBER |
| 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 | FUW 12, 24, 36, and 48 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. Number analyzed included participants with data available for analysis at that specified timepoint. Different participants may have contributed data for each timepoint. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time | 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 | mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. Number analyzed included participants with data available for analysis at that specified timepoint. | log10 IU/mL | MEAN |
| 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 | Predose on Day 1 and up to 168 hours post dose (Week 1) | PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample. | hours*nanomoles/liters (hr*nmol/L) | MEAN |
| SECONDARY | Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA | Predose on Day 1 and up to 168 hours post dose (Week 1) | PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample. | nanomoles/liters (nmol/L) | MEAN |
| SECONDARY | Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA | Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12) | PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample. | hr*nmol/L | MEAN |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 outcomesResults by group671
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | NUC Control Arm | 0 | 95% Confidence Interval 0 to 10 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 1: CpAM + TLR7 Agonist + NUC | 0 | 95% Confidence Interval 0 to 0 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 2: siRNA (100 mg) + NUC | 6.7 | 95% Confidence Interval 0.8 to 22.1 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 3: siRNA (200 mg) + NUC | 3.3 | 95% Confidence Interval 0.1 to 17.2 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 4: siRNA + PEG-IFN + NUC | 23.3 | 95% Confidence Interval 9.9 to 42.3 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 5: siRNA + CpAM + NUC | 0 | 95% Confidence Interval 0 to 0 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 6: siRNA + TLR7 Agonist + NUC | 11.8 | 95% Confidence Interval 3.3 to 27.5 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 7: siRNA + PD-L1 LNA + NUC | 0 | 95% Confidence Interval 0 to 10.6 | percentage of participants | |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT) | Combo 8: siRNA + PD-L1 LNA + NUC | 6.7 | 95% Confidence Interval 0.8 to 22.1 | percentage of participants | |
| Percentage of Participants With HBsAg Loss | Combo 1: CpAM + TLR7 Agonist + NUC | Week 24 | 0 | 95% Confidence Interval 0 to 0 | percentage of participants |
1 to 10 of 671Source ClinicalTrials.gov
See all 671 results by groupParticipant flow27
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | NUC Control Arm | 36 | |
| Overall Study | STARTED | Combo 1: CpAM + TLR7 Agonist + NUC | 38 | |
| Overall Study | STARTED | Combo 2: siRNA (100 mg) + NUC | 30 | |
| Overall Study | STARTED | Combo 3: siRNA (200 mg) + NUC | 30 | |
| Overall Study | STARTED | Combo 4: siRNA + PEG-IFN + NUC | 30 | |
| Overall Study | STARTED | Combo 5: siRNA + CpAM + NUC | 19 | |
| Overall Study | STARTED | Combo 6: siRNA + TLR7 Agonist + NUC | 34 | |
| Overall Study | STARTED | Combo 7: siRNA + PD-L1 LNA + NUC | 33 | |
| Overall Study | STARTED | Combo 8: siRNA + PD-L1 LNA + NUC | 31 | |
| Overall Study | COMPLETED | NUC Control Arm | 30 |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 participant flowAdverse events1,125
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Combo 1: CpAM + TLR7 Agonist + NUC | 0 | 38 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 2: siRNA (100 mg) + NUC | 0 | 30 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 3: siRNA (200 mg) + NUC | 1 | 30 | 1 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 4: siRNA + PEG-IFN + NUC | 0 | 30 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 5: siRNA + CpAM + NUC | 2 | 19 | 2 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 6: siRNA + TLR7 Agonist + NUC | 0 | 34 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 7: siRNA + PD-L1 LNA + NUC | 0 | 33 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | Combo 8: siRNA + PD-L1 LNA + NUC | 0 | 31 | 0 |
| other | Anaemia | Blood and lymphatic system disorders | NUC Control Arm | 0 | 35 | 0 |
| other | Lymphopenia | Blood and lymphatic system disorders | Combo 1: CpAM + TLR7 Agonist + NUC | 0 | 38 | 0 |
1 to 10 of 1,125Source ClinicalTrials.gov
See all 1,125 adverse eventsAdverse event totals27
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Combo 1: CpAM + TLR7 Agonist + NUC | 0 | 38 |
| Total, all-cause mortality | Combo 2: siRNA (100 mg) + NUC | 0 | 30 |
| Total, all-cause mortality | Combo 3: siRNA (200 mg) + NUC | 0 | 30 |
| Total, all-cause mortality | Combo 4: siRNA + PEG-IFN + NUC | 0 | 30 |
| Total, all-cause mortality | Combo 5: siRNA + CpAM + NUC | 0 | 19 |
| Total, all-cause mortality | Combo 6: siRNA + TLR7 Agonist + NUC | 0 | 34 |
| Total, all-cause mortality | Combo 7: siRNA + PD-L1 LNA + NUC | 0 | 33 |
| Total, all-cause mortality | Combo 8: siRNA + PD-L1 LNA + NUC | 0 | 31 |
| Total, all-cause mortality | NUC Control Arm | 0 | 35 |
| Total, other adverse events | Combo 1: CpAM + TLR7 Agonist + NUC | 33 | 38 |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons1
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison |
|---|
| Combo 7: siRNA + PD-L1 LNA + NUC vs Combo 8: siRNA + PD-L1 LNA + NUC: Combos 7 and 8: Number of Participants With Anti-PD-L1 Antibodies |
Source Trial comparisons
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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