Chronic Hepatitis b
Conditions
Brief summary
This is a randomized, double-blinded, placebo-controlled, multi center, dose ranging study of safety and efficacy in volunteers with chronic hepatitis B virus infection. Volunteers will be administered multiple oral doses of ATI-2173 vebicorvir in combination with tenofovir disoproxil fumarate and assessed for safety and efficacy including blood tests to show how the body metabolizes and eliminates the investigational drug as well as how the drug effects the virus infection.
Interventions
DRUGATI-2173 25mg
ATI-2173 is a liver-targeted phosphoramidate prodrug of clevudine designed to enhance anti-HBV activity while decreasing systemic exposure to clevudine. It will be dosed as a capsule by mouth.
DRUGVebicorvir 300mg
Vebicorvir (formerly ABI-H0731) is an orally administered, potent and selective small molecule inhibitor of the HBV core protein
DRUGViread 300Mg Tablet
Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.
Sponsors
Antios Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form (ICF) 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. If female, meets one of the following criteria: 1. Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include: * Abstinence from heterosexual intercourse from the first study drug administration through to at least 6 months after the last dose of the study drug or until completion of the study, whichever is longer * Use a non-hormonal intrauterine device, from at least 28 days prior to the first study drug administration through to at least 6 months after the last dose of the study drug or until completion of the study, whichever is longer, with a male condom or a diaphragm/cervical cap plus spermicide from the first study drug administration through to at least 30 days after the last dose of the study drug or until completion of the study, whichever is longer * Use of a double-barrier method * Male partner vasectomized at least 6 months prior to the first study drug administration Or 2. Is of non-childbearing potential, defined as surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (ie, at least 1 year without menses without an alternative medical condition prior to the first study drug administration and follicle-stimulating hormone \[FSH\] levels within the normal ranges for postmenopausal state of the clinical site at screening). If the subject engages in sexual relations, a barrier method (male or female condom) should be used to prevent the spread of HBV. 4. If male, meets one of the following criteria: a) Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration. An acceptable method of contraception includes one of the following: * Abstinence from heterosexual intercourse * Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository) Or c) Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 6 months prior to the first study drug administration). If the subject engages in sexual relations, a barrier method (male or female condom) should be used to prevent the spread of HBV. 5. Male or female aged at least 18 years but not older than 70 years 6. Body mass index (BMI) within 18.0 kg/m2 to 35.0 kg/m2, inclusively 7. Light-, non- or ex-smoker (A light smoker is defined as someone using 10.0 nicotine units or less per day for at least 90 days prior to the first study drug administration \[refer to APPENDIX 7 for conversions of nicotine usage\]. An ex-smoker is defined as someone who completely stopped using nicotine products for at least 6 months prior to the first study drug administration) 8. Serum HBsAg positive at screening and at least 6 months prior to screening. 9. Serum HBeAg positive and HBV DNA ≥ 20,000 IU/mL, or serum HBeAg negative and HBV DNA ≥ 2,000 IU/mL at screening 10. ALT and AST \< 5 times the upper limit of normal (ULN) at screening and on the day prior to the first study drug administration (Day -1)
Exclusion criteria
1. Female who is lactating at screening 2. Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration 3. History of significant hypersensitivity to clevudine, tenofovir disoproxil fumarate or any related products (including excipients of ATI-2173, tenofovir disoproxil fumarate, and the placebo) as well as severe hypersensitivity reactions (like angioedema) to any drugs 4. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease 5. Presence of clinically significant muscle disorders, myopathies or other forms of liver disease 6. Presence of any clinically significant disease, as captured in the medical history or evidence of findings on the physical examination, vital sign assessment and/or ECG assessment, and that would otherwise exclude subject from eligibility in the context of all other listed inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE) | Through study completion, an average of 1 year |
| The percentage of subjects who experienced at least 1 treatment-emergent serious adverse event (TE SAE) | Through study completion, an average of 1 year |
| The percentage of subjects who experienced a treatment-emergent dose-limiting toxicity (TE DLT) | Through study completion, an average of 1 year |
| The percentage of subjects who experienced at least 1 treatment-emergent Division of AIDS (DAIDS) Grade 1, 2, 3, 4, or 5 laboratory abnormality | Through study completion, an average of 1 year |
| The percentage of subjects who discontinued the study drug due to a TEAE | Through study completion, an average of 1 year |
| Alanine aminotransferase and aspartate aminotransferase levels versus time | Through study completion, an average of 1 year |
| Time to HBV viral load relapse in HBV-infected subjects as measured by HBV DNA viral load in IU/mL | Through study completion, an average of 1 year, which is 6 months after end of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with HBV DNA sustained viral response as measured by HBV DNA viral load at 6 months after end of treatment | Through study completion, an average of 1 year, which is 6 months after end of treatment |
| Cmax of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| Tmax of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| Ctrough of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| Ctau of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| AUC0-24 of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| AUCtau of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| t1/2 of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| RAC(Cmax) of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| RAC(AUC) of ATI-2173, clevudine and M1 in plasma | Through study completion, an average of 1 year |
| Proportion of subjects with HBV SVR12, SVR18, and SVR24months | Through study completion, an average of 1 year, or through 24 months if applicable |
| Proportion of subjects with on-treatment ALT flares | Through Day 90 |
| Proportion of subjects with off-treatment ALT flares | From Day 90 through end of study, about 6 months |
| Rate of HBV viral load return to baseline off-treatment | From Day 90 through end of study, about 6 months |
| Relationship between HBV RNA and HBV Sustained Viral Response at 6 months | Through study completion, an average of 1 year, which is 6 months after treatment |
| Change from baseline value in HBV RNA at end of treatment and Sustained Viral Response at 6 months | Through study completion, an average of 1 year, 6 months after treatment |
| Change from baseline in HBsAg over time and Sustained Viral Response at 6 months | Through study completion, an average of 1 year, 6 months after treatment |
| Change from baseline value in HBcrAg at end of treatment and Sustained Viral Response at 6 months | Through study completion, an average of 1 year, 6 months after treatment |
| Relationship between HBV DNA Sustained Viral Response and HBsAg | Through study completion, an average of 1 year |
| Reduction from baseline in HBsAg following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year |
| Reduction from baseline in HBV RNA following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year |
| Reduction from baseline in HBcrAg following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year |
| Cmax of tenofovir in plasma | Through study completion, an average of 1 year |
| Tmax of tenofovir in plasma | Through study completion, an average of 1 year |
| AUC0-24 of tenofovir in plasma | Through study completion, an average of 1 year |
| RAC(AUC) of tenofovir in plasma | Through study completion, an average of 1 year |
| Cmax of vebicorvir in plasma | Through study completion, an average of 1 year |
| Tmax of vebicorvir in plasma | Through study completion, an average of 1 year |
| Ctrough of vebicorvir in plasma | Through study completion, an average of 1 year |
| Ctau of vebicorvir in plasma | Through study completion, an average of 1 year |
| AUC0-24 of vebicorvir in plasma | Through study completion, an average of 1 year |
| t1/2 of vebicorvir in plasma | Through study completion, an average of 1 year |
| RAC(Cmax) of vebicorvir in plasma | Through study completion, an average of 1 year |
| RAC(AUC) of vebicorvir in plasma | Through study completion, an average of 1 year |
| Correlation between individual tie to viral load relapse and Day 90 clevudine, vebicorvir, and tenofovir Cmin and AUC | Through study completion, an average of 1 year |
| Correlation between SVR6 and Day 90 clevudine, vebicorvir, and tenofovir Cmin and AUC | Through study completion, an average of 1 year |
| Ctrough of tenofovir in plasma | Through study completion, an average of 1 year |
| t1/2 of tenofovir in plasma | Through study completion, an average of 1 year |
| RAC(Cmax) of tenofovir in plasma | Through study completion, an average of 1 year |
| Ctau of tenofovir in plasma | Through study completion, an average of 1 year |
| Baseline-adjusted maximal reduction in HBV DNA viral load (Emax,HBV) through 6 months after end of treatment following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year, which is 6 months after end of treatment |
| TEmax,HBV through 6 months after end of treatment following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year, which is 6 months after end of treatment |
| AUEC(HBV) through 6 months after end of treatment following ATI-2173 + vebicorvir + TDF or placebo + TDF for 90 days in HBV-infected subjects | Through study completion, an average of 1 year, which is 6 months after end of treatment |
Countries
Moldova, Ukraine
Outcome results
None listed