Chronic Hepatitis B
Conditions
Keywords
CHB (chronic hepatitis B infection), HBV (hepatitis B virus), HBeAg positive (hepatitis B e antigen - positive), HBeAg negative (hepatitis B e antigen - negative), Hepatitis B (hepatitis B virus), Hepatitis B virus (HBV), SVR (sustained viral response)
Brief summary
Open-label, extension study to evaluate the safety and efficacy of combination therapy and its effect on sustained viral response biomarkers.
Detailed description
This is an open-label extension of parent studies ABI-H0731-201 (NCT03576066) and ABI-H0731-202 (NCT03577171). The extension study will assess the safety of long-term (up to 100 weeks of treatment in extension study ABI-H0731-211) combination therapy and its effect on biomarkers of sustained viral response (SVR) (NCT03780543).
Interventions
DRUGstandard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)
Participants will continue on their SOC NrtI, Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) or Tenofovir Alafenamide (TAF) tablet QD (once daily) orally as per approved package insert.
Sponsors
Assembly Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide informed consent. 2. Previously enrolled on Study ABI-H0731-201 (NCT03576066) or ABI-H0731-202 (NCT03577171) and completed the treatment period, with demonstrated compliance in the opinion of the investigator. 3. Female subjects must agree to use an effective birth control method for the duration of the study and follow-up, or be surgically sterile for at least 6 months, or at least 2 years postmenopausal with serum follicle-stimulating hormone (FSH) levels consistent with a postmenopausal status. Effective birth control methods include male or female condom (may not be used together due to increased risk of breakage), vasectomy, intrauterine device (IUD), diaphragm, or cervical cap. Female subjects of childbearing potential must have a negative serum pregnancy test. 4. All heterosexually active male subjects must agree to use an effective birth control method for the duration of the study and follow-up. Effective birth control methods include male or female condom (may not be used together due to increased risk of breakage), vasectomy, hormone-based contraception (only female partner of a male subject), IUD, diaphragm, or cervical cap. 5. Agreement to adhere to Lifestyle Considerations (including abstaining from alcohol abuse \[defined as alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol)\] and the use of illicit substances, herbal or other substances, or unnecessary over-the-counter medications throughout study duration. 6. In good general health except for chronic HBV infection. 7. Have the ability to take oral medication and be willing to adhere to the ABI-H0731-211 regimen in the opinion of the Investigator.
Exclusion criteria
1. Must not have had evidence of HBV resistance-associated variants (RAVs) or lack of compliance on a previous study of ABI H0731. 2. Must not have had a treatment-emergent adverse event or laboratory abnormalities deemed clinically significant and possibly or probably related to drug while on a previous study of ABI-H0731, that in the opinion of the Investigator or the Sponsor makes the subject unsuitable for this study. 3. Current clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the subject unsuitable for the study. 4. Females who are lactating or pregnant or wish to become pregnant within the duration of the ABI-H0731-211 study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Viral Response (SVR) at 24 Weeks Off Treatment | Completing from week 52 until week 76 | To evaluate the potential for combination therapy with ABI-H0731+ NrtI to increase SVR rates in subjects who have chronic hepatitis B (CHB). To evaluate the proportion of subjects who meet the definition of SVR at 24 weeks off treatment, the SVR rate and corresponding 95% confidence interval will be presented for the overall population while on combination therapy. SVR is defined as sustained viral response with HBV DNA , LOQ (20 IU/mL) through off-treatment Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | Up to Week 148 | Incidence of treatment emergent adverse events (AEs) |
| Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | EOT: up to Week 52 or 148; EOS: up to 3 years off treatment | To measure the number and proportion of subjects with abnormal ALT at baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) To measure the number and proportion of subjects regardless of levels of ALT at baseline at EOT and EOS |
| Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | upto Week 148 | Incidence of subjects with suppression/loss of viral Hepatitis B e antigen (HBeAg) antigen/DNA on combination treatment whose viral antigens rebound off therapy |
| Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | Up to Week 148 | Incidence of subjects with suppression/loss of viral core-related antigen (HBcrAg) or DNA on combination treatment whose viral antigens rebound off treatment |
Countries
Canada, Hong Kong, New Zealand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Virologically Suppressed HBeAg-negative Participants From Parent Study ABI-H0731-201 Subjects who on Day 1 of parent study ABI-H0731-201 (NCT03576066) were standard of care nucleos(t)ide (SOC NrtI)-suppressed and HBeAg-negative will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time they will discontinue both ABI-H0731 and SOC NrtI and be monitored for up to 3 years.
ABI-H0731: Participants will receive 300 mg QD of ABI-H0731 tablets orally.
SOC NrtI: Participants will continue on their SOC NrtI (ETV, TDF or TAF) tablet QD orally as per approved package insert. | 26 |
| Virologically Suppressed HBeAg-positive Participants From Parent Study ABI-H0731-201 Subjects who on Day 1 of parent study ABI-H0731-201 (NCT03576066) were SOC NrtI-suppressed and HBeAg-positive will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time their viral response will be evaluated. Subjects who meet the virologic response criteria will discontinue both ABI-H0731 and SOC NrtI and be monitored for up to 3 years. Subjects with insufficient virologic response will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.
ABI-H0731: Participants will receive 300 mg QD of ABI-H0731 tablets orally.
SOC NrtI: Participants will continue on their SOC NrtI (ETV, TDF or TAF) tablet QD orally as per approved package insert. | 43 |
| HBeAg Positive Participants From Parent Study ABI-H0731-202 Subjects who on Day 1 of parent study ABI-H0731-202 (NCT03577171) were treatment-naive and HBeAg-positive will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time their viral response will be evaluated.
Subjects who meet the virologic response criteria at Week 52 will continue to receive ABI-H0731 + SOC NrtI for an additional 96 weeks, after which time their viral response will be evaluated at Week 148. Subjects who meet the virologic response criteria at Week 148 will discontinue both ABI-H0731 and SOC NrtI and be monitored for up to 3 years, while those subjects with insufficient virologic response will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.
Subjects with insufficient virologic response at Week 52 will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.
ABI-H0731: Participants will receive 300 mg QD of ABI-H0731 tablets orally.
SOC NrtI: Participants will continue on their SOC NrtI (ETV, TDF or TAF) tablet QD orally as per approved package insert. | 23 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Noncompliance with study drug | 1 | 0 | 0 |
| Overall Study | Study terminated by Sponsor | 8 | 7 | 13 |
| Overall Study | Withdrawal by Subject | 1 | 8 | 1 |
Baseline characteristics
| Characteristic | Virologically Suppressed HBeAg-negative Participants From Parent Study ABI-H0731-201 | Total | HBeAg Positive Participants From Parent Study ABI-H0731-202 | Virologically Suppressed HBeAg-positive Participants From Parent Study ABI-H0731-201 |
|---|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 7.8 | 44 years STANDARD_DEVIATION 12 | 36 years STANDARD_DEVIATION 13 | 45 years STANDARD_DEVIATION 11.7 |
| Body Mass Index | 24.38 kg/m 2 STANDARD_DEVIATION 2.922 | 23.96 kg/m 2 STANDARD_DEVIATION 3.496 | 23.47 kg/m 2 STANDARD_DEVIATION 3.984 | 23.97 kg/m 2 STANDARD_DEVIATION 3.583 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 80 Participants | 22 Participants | 38 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Canada | 0 Participants | 11 Participants | 3 Participants | 8 Participants |
| Region of Enrollment Hong Kong | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Region of Enrollment New Zealand | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 26 Participants | 73 Participants | 14 Participants | 33 Participants |
| Sex: Female, Male Female | 10 Participants | 40 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 16 Participants | 52 Participants | 8 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 43 | 0 / 23 |
| other Total, other adverse events | 5 / 26 | 12 / 43 | 4 / 23 |
| serious Total, serious adverse events | 0 / 26 | 0 / 43 | 1 / 23 |
Outcome results
Primary
Sustained Viral Response (SVR) at 24 Weeks Off Treatment
To evaluate the potential for combination therapy with ABI-H0731+ NrtI to increase SVR rates in subjects who have chronic hepatitis B (CHB). To evaluate the proportion of subjects who meet the definition of SVR at 24 weeks off treatment, the SVR rate and corresponding 95% confidence interval will be presented for the overall population while on combination therapy. SVR is defined as sustained viral response with HBV DNA , LOQ (20 IU/mL) through off-treatment Week 24.
Time frame: Completing from week 52 until week 76
Population: Participants who met the protocol-specific treatment action criteria to discontinue treatment with ABI-H0731 and NrtI after completing 52 weeks of treatment were analyzed for sustained viral repones at 24 weeks off treatment. (i.e., Completing from week 52 (treatment discharge) until week 76 (24 weeks off treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Sustained Viral Response (SVR) at 24 Weeks Off Treatment | 0 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Sustained Viral Response (SVR) at 24 Weeks Off Treatment | 0 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Sustained Viral Response (SVR) at 24 Weeks Off Treatment | 0 Participants |
Secondary
Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS)
To measure the number and proportion of subjects with abnormal ALT at baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) To measure the number and proportion of subjects regardless of levels of ALT at baseline at EOT and EOS
Time frame: EOT: up to Week 52 or 148; EOS: up to 3 years off treatment
Population: Number/proportion of subjects with normal alanine aminotransferase (ALT) at end of treatment (EOT) and end of study (EOS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Numbers with normal ALT levels at EOT | 2 Participants |
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Number with normal ALT levels at EOS | 1 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Numbers with normal ALT levels at EOT | 0 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Number with normal ALT levels at EOS | 0 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Numbers with normal ALT levels at EOT | 5 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS) | Number with normal ALT levels at EOS | 5 Participants |
Secondary
Number of Subjects With Adverse Events
Incidence of treatment emergent adverse events (AEs)
Time frame: Up to Week 148
Population: Safety population included all who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with significant abnormal ECGs | 0 Participants |
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with discontinuation due to an AE | 1 Participants |
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with AEs | 16 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with significant abnormal ECGs | 1 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with AEs | 26 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Adverse Events | Number of subjects with discontinuation due to an AE | 0 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Number of Subjects With Adverse Events | Number of subjects with significant abnormal ECGs | 0 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Number of Subjects With Adverse Events | Number of subjects with discontinuation due to an AE | 2 Participants |
| Treatment-naïve Subjects With HBeAg Positive cHBV | Number of Subjects With Adverse Events | Number of subjects with AEs | 12 Participants |
Secondary
Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
Incidence of subjects with suppression/loss of viral core-related antigen (HBcrAg) or DNA on combination treatment whose viral antigens rebound off treatment
Time frame: Up to Week 148
Population: Subjects from the parent study 201 with positive or negative Hepatitis B e antigen (HBeAg)~Treatment-naïve Subjects With HBeAg Positive cHBV was not collected. No entry has been made in the column.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | 7 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | 0 Participants |
Secondary
Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
Incidence of subjects with suppression/loss of viral Hepatitis B e antigen (HBeAg) antigen/DNA on combination treatment whose viral antigens rebound off therapy
Time frame: upto Week 148
Population: The proportion of subjects with hepatitis B virus (HBV) DNA target not detected (TND).~Treatment-naïve Subjects With HBeAg Positive cHBV was not collected. No entry has been made in the column.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Virologically-suppressed HBeAg Negative Participants From Parent Study ABI-H0731-201 | Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | 4 Participants |
| Virologically-suppressed HBeAg Positive Participants From Parent Study ABI-H0731-201 | Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy | 4 Participants |