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A Study of Safety and Efficacy of ATI-2173 in Combination With Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B Virus Infection and in Subjects With Hepatitis D Virus Coinfection

Primary Purpose

Hepatitis B, Chronic, Hepatitis D

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATI-2173
Viread
AB-729
Sponsored by
Antios Therapeutics, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

ALL SUBJECTS:

  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 systemic contraceptive or an intrauterine device (with or without hormones), 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
      • Male partner vasectomized at least 6 months prior to the first study drug administration OR
    2. Male partner has had a vasectomy less than 6 months prior to dosing, and the female subject agrees to use an additional acceptable contraceptive method 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 Or
    3. 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)
  4. If male, meets one of the following criteria:

    1. 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. Only for Cohort D: male subjects able to procreate must agree to use an accepted contraceptive regimen and not to donate sperm from the first study drug administration to at least 6 months 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
    2. Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 6 months prior to the first study drug administration)
  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. For Cohorts A, B and E only, 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)

    SUBJECTS COINFECTED WITH CHRONIC HBV AND HDV ONLY:

  11. HDV RNA in serum ≥ 500 IU/mL at screening and evidence of HDV infection (HDVAb or HDV RNA) at least 6 months prior to screening

    SUBJECTS IN COHORT D ONLY:

  12. Serum HBsAg levels ≥ 100 IU/mL at screening

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 exclusion criteria, as determined by an Investigator
  7. Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
  8. Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
  9. Any history of tuberculosis
  10. Active illicit drug use including, but not limited to, cocaine, heroin and methamphetamine (the use of cannabinoids is acceptable)
  11. Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
  12. Use of amiodarone in the 28 days prior to the first study drug administration
  13. Presence or history of clinically significant gastrointestinal or kidney disease, or surgery that may affect drug bioavailability
  14. Cirrhosis of the liver as determined by one of the following:

    • A score greater than F2 (or greater than F3 for HBV/HDV coinfected subjects) for liver fibrosis by FibroScan or FibroSure test within 6 months prior to screening or at the time of screening Or
    • A score greater than F2 (or greater than F3 for HBV/HDV coinfected subjects) on liver biopsy within 12 months prior to screening or at the time of screening
  15. History of or known presence of hepatocellular carcinoma
  16. Acute infection or any other clinically significant illness within 14 days of Day 1 of the study
  17. History of organ transplantation
  18. Presence of uncontrolled hypertension
  19. Positive screening results to HIV Ag/Ab combo or hepatitis C virus tests
  20. Any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
  21. Inclusion in another cohort for this clinical study
  22. Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration
  23. Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
  24. Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration
  25. Previous approved or investigational treatment for HBV or HDV, including nucleoside therapy, other than treatment by tenofovir or interferon alpha. Prior treatment with tenofovir or interferon alpha must have been discontinued at least 6 months prior to Screening.

    SUBJECTS WITH CHRONIC HBV (COHORTS A, B, AND D):

  26. Positive screening results to HDV tests

    SUBJECTS IN COHORT D ONLY:

  27. History of significant hypersensitivity to excipients of AB-729, any siRNAs, or antisense oligonucleotides (ASOs)

Sites / Locations

  • Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit
  • Medical Center of Limited Liability Company "Harmoniya krasy"

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

ATI-2173 and Viread

Placebo and Viread

ATI-2173, Viread and AB-729

Placebo, Viread and AB-729 Placebo

Arm Description

ATI-2173 + Tenofovir disoproxil fumarate (Viread)

ATI-2173 Placebo + Tenofovir disoproxil fumarate

ATI-2173 + Tenofovir disoproxil fumarate (Viread) + AB-729

ATI-2173 Placebo + Tenofovir disoproxil fumarate (Viread) + AB-729 Placebo

Outcomes

Primary Outcome Measures

The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE)
The percentage of subjects who experienced at least one treatment emergent serious AE (SAE).
Percentage of subjects who experienced a treatment-emergent dose limiting toxicity (DLT)
Percentage of subjects who experienced at least one treatment emergent Grade 1, 2, 3, 4 or 5 laboratory abnormality
Percentage of subjects who discontinued study drug due to a TEAE
Alanine aminotransferase and aspartate aminotransferase levels versus time
Time to HBV viral load relapse in HBV-infected subjects
The reduction of HDV RNA on-treatment for HBV/HDV coinfected subjects

Secondary Outcome Measures

TE(max, HBV) up to Day 90 and through end of study with or without AB-729 or placebo + tenofovir
AUEC(HBV) up to Day 90 and through end of study with or without AB-729 of placebo + tenofovir
TE(max, HDV) up to Day 90 and through end of study
AUEC(HDV) up to Day 90 and through end of study
Baseline-adjusted maximal reduction in HBV DNA viral load (Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects
Baseline-adjusted maximal reduction in HDV RNA viral load (Emax,HDV) through 6 months after end of treatment following ATI-2173 + tenofovir or placebo + tenofovir for 90 days in HBV/HDV coinfected subjects
Cmax of ATI-2173, clevudine, tenofovir and M1 in plasma
Tmax of ATI-2173, clevudine, tenofovir and M1 in plasma
Ctrough of ATI-2173, clevudine, tenofovir and M1 in plasma
Ctau of ATI-2173, clevudine, tenofovir and M1 in plasma
AUC0-24 of ATI-2173, clevudine, tenofovir and M1 in plasma
T1/2 of ATI-2173, clevudine, tenofovir and M1 in plasma
RAC(Cmax) of ATI-2173, clevudine, tenofovir and M1 in plasma
RAC(AUC) of ATI-2173, clevudine, tenofovir and M1 in plasma
Correlation between individual Day 90 clevudine and tenofovir Cmin and Emax,HBV or Emax, HDV of viral load
Proportion of subjects with HBV SVR6 by treatment arm
Proportion of subjects with HDV SVR6 by treatment arm (HBV/HDV coinfected subjects only)
Proportion of subjects by treatment arm with HBV SVR12, SVR18, and SVR24
Proportion of subjects by treatment arm with HDV SVR12, SVR18, and SVR24 (HBV/HDV coinfected subjects only)
Proportion of subjects by treatment arm with on-treatment ALT flares
Proportion of subjects by treatment arm with off-treatment ALT flares, with no on-treatment ALT flares by treatment arm
HBV DNA slope off-treatment
Effect on HBV pgRNA in subjects who reach SVR6 as measured by percentage of subjects by validated assay
HBV pgRNA at end of treatment by treatment arm
Effect on HBsAg in subjects who reach HBV SVR6 as measured by percentage of subjects by validated assay
T(Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV-infected subjects and in HBV/HDV coinfected subjects
AUEC(HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV-infected subjects and in HBV/HDV coinfected subjects
T(Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV/HDV coinfected subjects
AUEC(HDV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV/HDV coinfected subjects
Change from baseline in HBsAg, HBV pgRNA, and HBcrAg at end of treatment and SVR6 in HBV-infected and in HBV/HDV coinfected subjects by treatment arm
Reduction from baseline in HBsAg, HBV pgRNA, and HBcrAg following ATI-2173 + tenofovir (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects
Correlation between individual time to viral load relapse and Day 90 clevudine and/or tenofovir Cmin and AUC
Correlation between SVR6 and Day 90 clevudine and/or tenofovir Cmin and AUC

Full Information

First Posted
April 6, 2021
Last Updated
November 15, 2022
Sponsor
Antios Therapeutics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT04847440
Brief Title
A Study of Safety and Efficacy of ATI-2173 in Combination With Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B Virus Infection and in Subjects With Hepatitis D Virus Coinfection
Official Title
A Phase 2A Randomized, Double-blinded, Placebo-controlled, Multicenter, Dose Ranging Study of Safety and Efficacy of ATI-2173 in Combination With Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B Virus Infection and in Subjects With Hepatitis D Virus Coinfection
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Terminated by the Sponsor
Study Start Date
March 30, 2021 (Actual)
Primary Completion Date
September 1, 2022 (Actual)
Study Completion Date
September 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Antios Therapeutics, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a randomized, double-blinded, placebo-controlled, multi center, dose ranging study of safety and efficacy in both volunteers with chronic hepatitis B virus infection and in volunteers with hepatitis D virus coinfection. Volunteers will be administered multiple oral doses of ATI-2173 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic, Hepatitis D

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATI-2173 and Viread
Arm Type
Experimental
Arm Description
ATI-2173 + Tenofovir disoproxil fumarate (Viread)
Arm Title
Placebo and Viread
Arm Type
Active Comparator
Arm Description
ATI-2173 Placebo + Tenofovir disoproxil fumarate
Arm Title
ATI-2173, Viread and AB-729
Arm Type
Experimental
Arm Description
ATI-2173 + Tenofovir disoproxil fumarate (Viread) + AB-729
Arm Title
Placebo, Viread and AB-729 Placebo
Arm Type
Active Comparator
Arm Description
ATI-2173 Placebo + Tenofovir disoproxil fumarate (Viread) + AB-729 Placebo
Intervention Type
Drug
Intervention Name(s)
ATI-2173
Intervention Description
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. Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.
Intervention Type
Drug
Intervention Name(s)
Viread
Other Intervention Name(s)
tenofovir disoproxil fumarate
Intervention Description
Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.
Intervention Type
Drug
Intervention Name(s)
AB-729
Intervention Description
AB-729 is a potent, selective, subcutaneously administered, N-acetylgalactosamine (Ga1NAc)-conjugated small interfering ribonucleic acid (siRNA) inhibitor of HBV
Primary Outcome Measure Information:
Title
The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE)
Time Frame
Through study completion, an average of 1 year
Title
The percentage of subjects who experienced at least one treatment emergent serious AE (SAE).
Time Frame
Through study completion, an average of 1 year
Title
Percentage of subjects who experienced a treatment-emergent dose limiting toxicity (DLT)
Time Frame
Through study completion, an average of 1 year
Title
Percentage of subjects who experienced at least one treatment emergent Grade 1, 2, 3, 4 or 5 laboratory abnormality
Time Frame
Through study completion, an average of 1 year
Title
Percentage of subjects who discontinued study drug due to a TEAE
Time Frame
Through study completion, an average of 1 year
Title
Alanine aminotransferase and aspartate aminotransferase levels versus time
Time Frame
Through study completion, an average of 1 year
Title
Time to HBV viral load relapse in HBV-infected subjects
Time Frame
Through study completion, an average of 1 year
Title
The reduction of HDV RNA on-treatment for HBV/HDV coinfected subjects
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
TE(max, HBV) up to Day 90 and through end of study with or without AB-729 or placebo + tenofovir
Time Frame
Through study completion, an average of 1 year
Title
AUEC(HBV) up to Day 90 and through end of study with or without AB-729 of placebo + tenofovir
Time Frame
Through study completion, an average of 1 year
Title
TE(max, HDV) up to Day 90 and through end of study
Time Frame
Through study completion, an average of 1 year
Title
AUEC(HDV) up to Day 90 and through end of study
Time Frame
Through study completion, an average of 1 year
Title
Baseline-adjusted maximal reduction in HBV DNA viral load (Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects
Time Frame
Through study completion at 6 months follow up
Title
Baseline-adjusted maximal reduction in HDV RNA viral load (Emax,HDV) through 6 months after end of treatment following ATI-2173 + tenofovir or placebo + tenofovir for 90 days in HBV/HDV coinfected subjects
Time Frame
Through study completion at 6 months follow up
Title
Cmax of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
Tmax of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
Ctrough of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
Ctau of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
AUC0-24 of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
T1/2 of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
RAC(Cmax) of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
RAC(AUC) of ATI-2173, clevudine, tenofovir and M1 in plasma
Time Frame
Through Day 120
Title
Correlation between individual Day 90 clevudine and tenofovir Cmin and Emax,HBV or Emax, HDV of viral load
Time Frame
Through Day 90
Title
Proportion of subjects with HBV SVR6 by treatment arm
Time Frame
Through study completion, an average of 1 year
Title
Proportion of subjects with HDV SVR6 by treatment arm (HBV/HDV coinfected subjects only)
Time Frame
Through study completion, an average of 1 year
Title
Proportion of subjects by treatment arm with HBV SVR12, SVR18, and SVR24
Time Frame
Through study completion, an average of 1 year
Title
Proportion of subjects by treatment arm with HDV SVR12, SVR18, and SVR24 (HBV/HDV coinfected subjects only)
Time Frame
Through study completion, an average of 1 year
Title
Proportion of subjects by treatment arm with on-treatment ALT flares
Time Frame
Through Day 90
Title
Proportion of subjects by treatment arm with off-treatment ALT flares, with no on-treatment ALT flares by treatment arm
Time Frame
From Day 90 through end of study, an average of 1 year
Title
HBV DNA slope off-treatment
Time Frame
Through end of study, an average of 1 year
Title
Effect on HBV pgRNA in subjects who reach SVR6 as measured by percentage of subjects by validated assay
Time Frame
Through end of study, an average of 1 year
Title
HBV pgRNA at end of treatment by treatment arm
Time Frame
Through Day 90
Title
Effect on HBsAg in subjects who reach HBV SVR6 as measured by percentage of subjects by validated assay
Time Frame
Through end of study, an average of 1 year
Title
T(Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV-infected subjects and in HBV/HDV coinfected subjects
Time Frame
Through end of study, an average of 1 year
Title
AUEC(HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV-infected subjects and in HBV/HDV coinfected subjects
Time Frame
Through end of study, an average of 1 year
Title
T(Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV/HDV coinfected subjects
Time Frame
Through end of study, an average of 1 year
Title
AUEC(HDV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV/HDV coinfected subjects
Time Frame
Through end of study, an average of 1 year
Title
Change from baseline in HBsAg, HBV pgRNA, and HBcrAg at end of treatment and SVR6 in HBV-infected and in HBV/HDV coinfected subjects by treatment arm
Time Frame
Through end of study, an average of 1 year
Title
Reduction from baseline in HBsAg, HBV pgRNA, and HBcrAg following ATI-2173 + tenofovir (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects
Time Frame
Through end of study, an average of 1 year
Title
Correlation between individual time to viral load relapse and Day 90 clevudine and/or tenofovir Cmin and AUC
Time Frame
Through Day 90
Title
Correlation between SVR6 and Day 90 clevudine and/or tenofovir Cmin and AUC
Time Frame
Through Day 90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ALL SUBJECTS: Provision of signed and dated informed consent form (ICF) Stated willingness to comply with all study procedures and availability for the duration of the study If female, meets one of the following criteria: 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 systemic contraceptive or an intrauterine device (with or without hormones), 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 Male partner vasectomized at least 6 months prior to the first study drug administration OR Male partner has had a vasectomy less than 6 months prior to dosing, and the female subject agrees to use an additional acceptable contraceptive method 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 Or 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 male, meets one of the following criteria: 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. Only for Cohort D: male subjects able to procreate must agree to use an accepted contraceptive regimen and not to donate sperm from the first study drug administration to at least 6 months 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 Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 6 months prior to the first study drug administration) Male or female aged at least 18 years but not older than 70 years Body mass index (BMI) within 18.0 kg/m2 to 35.0 kg/m2, inclusively 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) Serum HBsAg positive at screening and at least 6 months prior to screening For Cohorts A, B and E only, serum HBeAg positive and HBV DNA ≥ 20,000 IU/mL, or serum HBeAg negative and HBV DNA ≥ 2,000 IU/mL at screening 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) SUBJECTS COINFECTED WITH CHRONIC HBV AND HDV ONLY: HDV RNA in serum ≥ 500 IU/mL at screening and evidence of HDV infection (HDVAb or HDV RNA) at least 6 months prior to screening SUBJECTS IN COHORT D ONLY: Serum HBsAg levels ≥ 100 IU/mL at screening Exclusion Criteria: Female who is lactating at screening Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration 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 History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease Presence of clinically significant muscle disorders, myopathies or other forms of liver disease 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 exclusion criteria, as determined by an Investigator Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration Any history of tuberculosis Active illicit drug use including, but not limited to, cocaine, heroin and methamphetamine (the use of cannabinoids is acceptable) Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) Use of amiodarone in the 28 days prior to the first study drug administration Presence or history of clinically significant gastrointestinal or kidney disease, or surgery that may affect drug bioavailability Cirrhosis of the liver as determined by one of the following: A score greater than F2 (or greater than F3 for HBV/HDV coinfected subjects) for liver fibrosis by FibroScan or FibroSure test within 6 months prior to screening or at the time of screening Or A score greater than F2 (or greater than F3 for HBV/HDV coinfected subjects) on liver biopsy within 12 months prior to screening or at the time of screening History of or known presence of hepatocellular carcinoma Acute infection or any other clinically significant illness within 14 days of Day 1 of the study History of organ transplantation Presence of uncontrolled hypertension Positive screening results to HIV Ag/Ab combo or hepatitis C virus tests Any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data Inclusion in another cohort for this clinical study Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration Previous approved or investigational treatment for HBV or HDV, including nucleoside therapy, other than treatment by tenofovir or interferon alpha. Prior treatment with tenofovir or interferon alpha must have been discontinued at least 6 months prior to Screening. SUBJECTS WITH CHRONIC HBV (COHORTS A, B, AND D): Positive screening results to HDV tests SUBJECTS IN COHORT D ONLY: History of significant hypersensitivity to excipients of AB-729, any siRNAs, or antisense oligonucleotides (ASOs)
Facility Information:
Facility Name
Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit
City
Chisinau
State/Province
Republic Of Moldova
Country
Moldova, Republic of
Facility Name
Medical Center of Limited Liability Company "Harmoniya krasy"
City
Kyiv
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of Safety and Efficacy of ATI-2173 in Combination With Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B Virus Infection and in Subjects With Hepatitis D Virus Coinfection

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