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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2
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.
Vebicorvir (formerly ABI-H0731) is an orally administered, potent and selective small molecule inhibitor of the HBV core protein
Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.
Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit
Chisinau, Republic of Moldova, Moldova
Medical Center of Limited Liability Company "Harmoniya krasy"
Kyiv, Ukraine
The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE)
Time frame: Through study completion, an average of 1 year
The percentage of subjects who experienced at least 1 treatment-emergent serious adverse event (TE SAE)
Time frame: Through study completion, an average of 1 year
The percentage of subjects who experienced a treatment-emergent dose-limiting toxicity (TE DLT)
Time frame: 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
Time frame: Through study completion, an average of 1 year
The percentage of subjects who discontinued the study drug due to a TEAE
Time frame: Through study completion, an average of 1 year
Alanine aminotransferase and aspartate aminotransferase levels versus time
Time frame: 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
Time frame: Through study completion, an average of 1 year, which is 6 months after end of treatment
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
Time frame: 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
Time frame: 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
Time frame: Through study completion, an average of 1 year, which is 6 months after end of treatment
Proportion of subjects with HBV DNA sustained viral response as measured by HBV DNA viral load at 6 months after end of treatment
Time frame: 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
Time frame: Through study completion, an average of 1 year
Tmax of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
Ctrough of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
Ctau of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
AUC0-24 of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
AUCtau of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
t1/2 of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
RAC(Cmax) of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
RAC(AUC) of ATI-2173, clevudine and M1 in plasma
Time frame: Through study completion, an average of 1 year
Proportion of subjects with HBV SVR12, SVR18, and SVR24months
Time frame: Through study completion, an average of 1 year, or through 24 months if applicable
Proportion of subjects with on-treatment ALT flares
Time frame: Through Day 90
Proportion of subjects with off-treatment ALT flares
Time frame: From Day 90 through end of study, about 6 months
Rate of HBV viral load return to baseline off-treatment
Time frame: From Day 90 through end of study, about 6 months
Relationship between HBV RNA and HBV Sustained Viral Response at 6 months
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Through study completion, an average of 1 year, 6 months after treatment
Relationship between HBV DNA Sustained Viral Response and HBsAg
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Through study completion, an average of 1 year
Cmax of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
Tmax of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
Ctrough of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
Ctau of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
AUC0-24 of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
t1/2 of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
RAC(Cmax) of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
RAC(AUC) of tenofovir in plasma
Time frame: Through study completion, an average of 1 year
Cmax of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
Tmax of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
Ctrough of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
Ctau of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
AUC0-24 of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
t1/2 of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
RAC(Cmax) of vebicorvir in plasma
Time frame: Through study completion, an average of 1 year
RAC(AUC) of vebicorvir in plasma
Time frame: 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
Time frame: Through study completion, an average of 1 year
Correlation between SVR6 and Day 90 clevudine, vebicorvir, and tenofovir Cmin and AUC
Time frame: Through study completion, an average of 1 year
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