E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A serious liver viral infection. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the potential for combination therapy with ABI-H0731 + SOC NUC to increase SVR rates in subjects who have CHB. SVR rates will be measured by percentage of subjects with the combination of: HBeAg loss (when applicable), loss or reduction to a stable plateau of HBsAg, and sustained loss of serum viral DNA |
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E.2.2 | Secondary objectives of the trial |
To evaluate the longer-term safety and tolerability of ABI-H0731 added to SOC NUC therapy • To evaluate improvement in transaminases in subjects on treatment and post treatment • For subjects who do not achieve complete response on treatment, to evaluate the durability of changes in viral antigen and viral DNA after discontinuation of combination therapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to provide informed consent. 2. Previously enrolled on a study of ABI-H0731 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 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; see Protocol Section 5.4) throughout study duration. 6. In good general health except for chronic HBV infection. Protocol ABI-H0731-211 OLE ABI-H0731 + NUC for CHB Patients Confidential Original Version 1.1, 02 November 2018 Page 9 of 89 7. Have the ability to take oral medication and be willing to adhere to the ABIH0731-211 regimen in the opinion of the Investigator |
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E.4 | Principal exclusion criteria |
Must not have had evidence of 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
SVR at 24 weeks off treatment defined as: sustained HBeAg loss (in HBeAg positive subjects), sustained viral suppression, and loss or stable reduction of HBsAg to ≤ 100 IU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be will be analyzed descriptively. For continuous variables, such as change from Baseline in mean log10 serum HBeAg or HBsAg values at each timepoint, descriptive statistics will be used and will include the number, mean, standard deviation, median, minimum, and maximum and, where appropriate, a 95% CI. |
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E.5.2 | Secondary end point(s) |
Adverse events, premature discontinuations, abnormal safety laboratory results, electrocardiogram (ECG), or vital signs • Subjects with abnormal ALT at Baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) • Subjects with suppression/loss of viral antigen/DNA on combination treatment whose viral antigens rebound off therapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be will be analyzed descriptively. For continuous variables, such as change from Baseline in mean log10 serum HBeAg or HBsAg values at each timepoint, descriptive statistics will be used and will include the number, mean, standard deviation, median, minimum, and maximum and, where appropriate, a 95% CI. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Hong Kong |
New Zealand |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be completed when the last subject completes the last post-treatment follow-up visit or when the last subject discontinues the study before completing the follow-up visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |