Open-Label Extension of ABI-H0731 for treatment of chronic hep B
Research type
Research Study
Full title
A Multi-center, Open-label, Long-term Extension Study of ABI-H0731 + Nucleos(t)ide as Finite Treatment for Chronic Hepatitis B Patients
IRAS ID
257304
Contact name
Kosh Agarwal
Contact email
Sponsor organisation
Assembly Biosciences Inc.
Eudract number
2018-004019-34
Clinicaltrials.gov Identifier
IND, 136780
Duration of Study in the UK
years, 24 months, days
Research summary
Research Summary:
Chronic hepatitis B infection (CHB), a major global cause of severe liver morbidity and liver-related mortality is due to the inflammation in the liver which can lead to severe liver disease, liver cancer or death in some patients. Current treatments for CHB can suppress the infection and liver disease. However, without long term treatment or re-treatment, options lead to a lasting benefit in only a small portion of patients.ABI-H0731 is an experimental medication which has shown to be safe and stop the spread of virus in patients with CHB when given for up to 28 days. ABI-H0731 has the potential to be an effective treatment for chronic HBV infection and potentially lower the amount of HBV even lower than existing medications on their own.
The purpose of this study is to assess the safety and tolerability of long-term ABI-H0731 treatment in patients with CHB, as well as the potential for ABI-H0731 to give sustained viral responses in patients who respond well to combination treatment. All participants will receive ABI-H0731 in combination with a standard of care nucleoside/nucleotide analogues targeting the HBV polymerase/reverse transcriptase (Nuc).
100 participants, aged 18 to 70, who have taken part in a previous ABI-H0731 study will participate. During this extension study, participants will receive ABI-H0731 for 24-52 weeks and current standard HBV medication. How long participants will receive ABI-H0731 depends on how the virus responds to treatment. Participants may have an additional 6 months to 3 years of safety follow-up visits after the 24-52 weeks, depending on virus response. Participation could last from 10 months to 3 years, could involve at least 12 to 35 visits. The total number of visits will depend on the response.
Study procedures include, but are not limited to, ECGs; liver ultrasound; blood and urine samples; physical examinations and questionnaires.
Lay Summary of Study Results: ABI-H0731-211 (Study 211) was an open-label extension study to assess the long-term safety and antiviral activity of the hepatitis B core inhibitor, vebicorvir (VBR), when administered in combination with a standard of care nucleos(t)ide reverse transcriptase inhibitor (NrtI). The study provided extended treatment to eligible subjects who had previously participated in one of two Phase 2 studies; ABI-H0731-201 (Study 201; virologically suppressed) and ABI-H0731-202 (Study 202; treatment-naive).
A total of 92 subjects (69 from Study 201; 23 from Study 202) were enrolled at 24 sites in the United States. All 92 subjects received oral administration of 300 mg VBR and a NrtI for up to 148 weeks. Subjects meeting protocol-defined virologic response criteria discontinued all treatment and entered an off-treatment follow-up period. Those subjects failing to meet stopping criteria discontinued VBR only and remained on standard of care NrtI treatment during follow-up. The primary endpoint of the study was the proportion of subjects with sustained virologic response (SVR) 24 weeks after discontinuation of all treatment (where applicable).
A total of 92 subjects (69 from Study 201; 23 from Study 202) were enrolled across 24 sites globally. A total of 70% (64/92) of subjects completed study drug treatment; the most common reasons for discontinuation of study drug were Study Terminated by Sponsor (14/92; 15%) and Withdrawal by Subject (8/92; 9%). A total of 51% (47/92) of subjects completed the study; the most common reasons for discontinuation study were Study Terminated by Sponsor (28/92; 30%) and Withdrawal by Subject (10/92; 11%).
In the study, VBR treatment in addition to NrtI therapy led to deep viral suppression as evidenced by reductions in HBV DNA and HBV pgRNA, and to a lesser degree, reductions in viral antigens.
- The observed on-treatment change in viral parameters varied by the patient population and Study 211 Baseline values.
- There was no evidence of treatment-emergent virologic resistance in subjects who were compliant to study drug.Among the subset of subjects who met criteria to discontinue all antiviral treatment, none achieved SVR. The primary endpoint was not met.
VBR administered in combination with NrtI was generally safe and well-tolerated with few discontinuations due to AEs and SAEs and no deaths. Most Grade 3 and 4 AEs and laboratory abnormalities were related to elevations in ALT and occurred in the Off-Treatment or NrtI-Restart Phases. No trends in safety in terms of vital signs, ECG, or physical examination were noted.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
19/SC/0028
Date of REC Opinion
28 Feb 2019
REC opinion
Further Information Favourable Opinion