Hepatitis B, Chronic
Conditions
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Brief summary
This is a Phase 1b/2 platform study framework to evaluate the safety and efficacy of investigational candidate(s) and their combinations as potential treatments for adults with chronic hepatitis B virus infection.
Detailed description
VIR-SHB1-V201 (STRIVE) Sub-Protocol A is a Phase 2 study under the PREVAIL platform trial. This is a multi-center, open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434, VIR-2218, PEGASYS (PEG-IFNα), and nucleotide reverse transcriptase inhibitors (NRTI) in noncirrhotic adult participants with chronic HBV infection that have not received prior NRTI or PEGASYS treatment. VIR-SHB1-V202 (THRIVE) Sub-Protocol B is a Phase 2 study under the PREVAIL platform trial. This is a multi-center open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434 and NRTI with or without VIR-2218 in noncirrhotic adult participants with low viral burden of chronic HBV infection.
Interventions
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ages 18 or older * Chronic HBV infection for \>/= 6 months * Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on 2 occasions at least 6 months apart based on previous or current laboratory documentation * STRIVE: HBeAg positive or negative, HBV DNA \> 2,000 IU/mL, ALT \> ULN and ≤ 5x ULN * THRIVE: Must be/have the following, within the 1-year period prior to screening: HBeAg negative, HBV DNA ≤ 2,000 IU/mL, ALT ≤ ULN
Exclusion criteria
* Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation * History of clinically significant liver disease from non-HBV etiology * History or current evidence of hepatic decompensation * Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV). * History or clinical evidence of alcohol or drug abuse * STRIVE and THRIVE: Significant fibrosis or cirrhosis * STRIVE and THRIVE: History of immune complex disease * STRIVE and THRIVE: History of autoimmune disorder * STRIVE and THRIVE: History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434 * STRIVE: Prior NRTI or PEG-IFN therapy * STRIVE: History of known contraindication to any interferon product * THRIVE: Prior NRTI therapy \< 24 weeks of study or any prior PEG-IFN therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment | Up to 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| STRIVE and THRIVE: Time to Achieve Nadir of Serum HBsAg During the Study | Up to 96 weeks |
| STRIVE and THRIVE: Time to Achieve Serum HBsAg Loss (< 0.05 IU/mL) | Up to 96 weeks |
| STRIVE and THRIVE: Proportion of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 96 weeks |
| STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at End of Treatment | Up to 48 weeks |
| STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at 24 Weeks Post-end of Treatment | Up to 72 weeks |
| STRIVE and THRIVE: Serum HBsAg Levels and Change From Baseline Across Timepoints in the Study | Up to 96 weeks |
| STRIVE and THRIVE: Proportion of Participants With HBsAg Loss With Anti-HBs Seroconversion at End of Treatment and at 24 Weeks Post-end of Treatment | Up to 76 weeks |
| STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit | Up to 96 weeks |
| STRIVE: Proportion of Participants With HBsAg Loss (<0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment | Up to 72 weeks |
| STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit | Up to 96 weeks |
| STRIVE: For HBeAg-positive Participants: Proportion of Participants With HBeAg Loss (Undetectable HBeAg) and/or Anti-HBe Seroconversion | Up to 72 weeks |
| STRIVE: Incidence and Titers of Anti-drug Antibodies (ADA; if Applicable) to VIR-3434 | Up to 96 weeks |
| STRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study | Up to 96 weeks |
| STRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ) Across Timepoints in the Study | Up to 96 weeks |
| STRIVE: Proportion of Participants Achieving ALT ≤ ULN Across Timepoints in the Study | Up to 96 weeks |
| THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks | Up to 92 weeks |
| THRIVE: Proportion of Participants Achieving HBsAg Loss (< 0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment | Up to 44 weeks |
| THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks | Up to 68 weeks |
| THRIVE: Incidence and Titers of ADA (if Applicable) to VIR-3434 | Up to 92 weeks |
| THRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study | Up to 92 weeks |
| STRIVE and THRIVE: Serum HBsAg Level at Nadir During the Study | Up to 96 weeks |
| THRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ) | Up to 92 weeks |
Countries
France, Hong Kong, Moldova, Romania, South Korea, United Kingdom
Participant flow
Pre-assignment details
Participants were not enrolled in Cohort 1a, 2a,3a, 5a and 1b Arms/Groups
Participants by arm
| Arm | Count |
|---|---|
| STRIVE: Cohort 1a (VIR-3434 + TDF) Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
TDF: TDF given orally | 0 |
| STRIVE: Cohort 2a (VIR-3434 + TDF) Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
TDF: TDF given orally | 0 |
| STRIVE: Cohort 3a (VIR-3434 + TDF) Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
TDF: TDF given orally | 0 |
| STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
VIR-2218: VIR-2218 given by subcutaneous injection
TDF: TDF given orally | 16 |
| STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
VIR-2218: VIR-2218 given by subcutaneous injection
TDF: TDF given orally
PEG-IFNα: PEG-IFNα given by subcutaneous injection | 0 |
| THRIVE: Cohort 1b (VIR-3434 + TDF) Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks
VIR-3434: VIR-3434 given by subcutaneous injection
TDF: TDF given orally | 0 |
| THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total
VIR-3434: VIR-3434 given by subcutaneous injection
VIR-2218: VIR-2218 given by subcutaneous injection
TDF: TDF given orally | 17 |
| Total | 33 |
Baseline characteristics
| Characteristic | STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) | THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) | Total | STRIVE: Cohort 1a (VIR-3434 + TDF) | STRIVE: Cohort 2a (VIR-3434 + TDF) | STRIVE: Cohort 3a (VIR-3434 + TDF) | STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) | THRIVE: Cohort 1b (VIR-3434 + TDF) |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 17 Participants | 33 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants | 0 Participants |
| Age, Continuous STRIVE: Cohort 4a | — | 0 years STANDARD_DEVIATION 0 | 43.3 years STANDARD_DEVIATION 9.67 | — | — | — | 43.3 years STANDARD_DEVIATION 9.67 | — |
| Age, Continuous THRIVE: Cohort 2b | — | 48.4 years STANDARD_DEVIATION 9.78 | 48.4 years STANDARD_DEVIATION 9.78 | — | — | — | 0 years STANDARD_DEVIATION 0 | — |
| Alanine Aminotransferase (U/L) STRIVE: Cohort 4a | — | 0 U/L STANDARD_DEVIATION 0 | 50.4 U/L STANDARD_DEVIATION 33.26 | — | — | — | 50.4 U/L STANDARD_DEVIATION 33.26 | — |
| Alanine Aminotransferase (U/L) THRIVE: Cohort 2b | — | 25.3 U/L STANDARD_DEVIATION 20.61 | 25.3 U/L STANDARD_DEVIATION 20.61 | — | — | — | 0 U/L STANDARD_DEVIATION 0 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 17 Participants | 33 Participants | — | — | — | 16 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Hepatitis B e antigen status HBeAg negative | — | 17 Participants | 30 Participants | — | — | — | 13 Participants | — |
| Hepatitis B e antigen status HBeAg positive | — | 0 Participants | 3 Participants | — | — | — | 3 Participants | — |
| Hepatitis B surface antigen (Log10 IU/mL) STRIVE: Cohort 4a | — | 0 Log10 IU/mL STANDARD_DEVIATION 0 | 3.64 Log10 IU/mL STANDARD_DEVIATION 0.72 | — | — | — | 3.64 Log10 IU/mL STANDARD_DEVIATION 0.72 | — |
| Hepatitis B surface antigen (Log10 IU/mL) THRIVE: Cohort 2b | — | 3.12 Log10 IU/mL STANDARD_DEVIATION 0.66 | 3.12 Log10 IU/mL STANDARD_DEVIATION 0.66 | — | — | — | 0 Log10 IU/mL STANDARD_DEVIATION 0 | — |
| Hepatitis B Virus DNA (Log10 IU/mL) STRIVE: Cohort 4a | — | 0 Log10 IU/mL STANDARD_DEVIATION 0 | 5.21 Log10 IU/mL STANDARD_DEVIATION 1.71 | — | — | — | 5.21 Log10 IU/mL STANDARD_DEVIATION 1.71 | — |
| Hepatitis B Virus DNA (Log10 IU/mL) THRIVE: Cohort 2b | — | 2.61 Log10 IU/mL STANDARD_DEVIATION 0.7 | 2.61 Log10 IU/mL STANDARD_DEVIATION 0.7 | — | — | — | 0 Log10 IU/mL STANDARD_DEVIATION 0 | — |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Race (NIH/OMB) Asian | — | 7 Participants | 13 Participants | — | — | — | 6 Participants | — |
| Race (NIH/OMB) Black or African American | — | 5 Participants | 7 Participants | — | — | — | 2 Participants | — |
| Race (NIH/OMB) More than one race | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | 1 Participants | — | — | — | 1 Participants | — |
| Race (NIH/OMB) White | — | 5 Participants | 12 Participants | — | — | — | 7 Participants | — |
| Region of Enrollment France | — | 3 Participants | 5 Participants | — | — | — | 2 Participants | — |
| Region of Enrollment Hong Kong | — | 2 Participants | 6 Participants | — | — | — | 4 Participants | — |
| Region of Enrollment Moldova | — | 2 Participants | 2 Participants | — | — | — | 0 Participants | — |
| Region of Enrollment New Zealand | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Region of Enrollment Romania | — | 2 Participants | 8 Participants | — | — | — | 6 Participants | — |
| Region of Enrollment South Korea | — | 5 Participants | 6 Participants | — | — | — | 1 Participants | — |
| Region of Enrollment Thailand | — | 0 Participants | 0 Participants | — | — | — | 0 Participants | — |
| Region of Enrollment United Kingdom | — | 3 Participants | 6 Participants | — | — | — | 3 Participants | — |
| Sex: Female, Male Female | — | 9 Participants | 19 Participants | — | — | — | 10 Participants | — |
| Sex: Female, Male Male | — | 8 Participants | 14 Participants | — | — | — | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 16 | 0 / 0 | 0 / 17 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 11 / 16 | 0 / 0 | 0 / 0 | 12 / 17 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 16 | 0 / 0 | 0 / 0 | 1 / 17 |
Outcome results
Primary
STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment
Time frame: Up to 48 weeks
Population: Cohort 1a, 2a, 3a,5a and 1b was not opened for enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) | STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment | 1 Participants |
| THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) | STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment | 4 Participants |
Secondary
STRIVE and THRIVE: Proportion of Participants With HBsAg Loss With Anti-HBs Seroconversion at End of Treatment and at 24 Weeks Post-end of Treatment
Time frame: Up to 76 weeks
Secondary
STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at 24 Weeks Post-end of Treatment
Time frame: Up to 72 weeks
Secondary
STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at End of Treatment
Time frame: Up to 48 weeks
Secondary
STRIVE and THRIVE: Proportion of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 96 weeks
Secondary
STRIVE and THRIVE: Serum HBsAg Level at Nadir During the Study
Time frame: Up to 96 weeks
Secondary
STRIVE and THRIVE: Serum HBsAg Levels and Change From Baseline Across Timepoints in the Study
Time frame: Up to 96 weeks
Secondary
STRIVE and THRIVE: Time to Achieve Nadir of Serum HBsAg During the Study
Time frame: Up to 96 weeks
Secondary
STRIVE and THRIVE: Time to Achieve Serum HBsAg Loss (< 0.05 IU/mL)
Time frame: Up to 96 weeks
Secondary
STRIVE: For HBeAg-positive Participants: Proportion of Participants With HBeAg Loss (Undetectable HBeAg) and/or Anti-HBe Seroconversion
Time frame: Up to 72 weeks
Secondary
STRIVE: Incidence and Titers of Anti-drug Antibodies (ADA; if Applicable) to VIR-3434
Time frame: Up to 96 weeks
Secondary
STRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study
Time frame: Up to 96 weeks
Secondary
STRIVE: Proportion of Participants Achieving ALT ≤ ULN Across Timepoints in the Study
Time frame: Up to 96 weeks
Secondary
STRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ) Across Timepoints in the Study
Time frame: Up to 96 weeks
Secondary
STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit
Time frame: Up to 96 weeks
Secondary
STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit
Time frame: Up to 96 weeks
Secondary
STRIVE: Proportion of Participants With HBsAg Loss (<0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment
Time frame: Up to 72 weeks
Secondary
THRIVE: Incidence and Titers of ADA (if Applicable) to VIR-3434
Time frame: Up to 92 weeks
Secondary
THRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study
Time frame: Up to 92 weeks
Secondary
THRIVE: Proportion of Participants Achieving HBsAg Loss (< 0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment
Time frame: Up to 44 weeks
Secondary
THRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ)
Time frame: Up to 92 weeks
Secondary
THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks
Time frame: Up to 68 weeks
Secondary
THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks
Time frame: Up to 92 weeks