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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

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ClinicalTrials.gov Identifier: NCT04847440
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : May 26, 2021
Sponsor:
Information provided by (Responsible Party):
Antios Therapeutics, Inc

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.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Hepatitis D Drug: ATI-2173 Drug: Viread Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 30, 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: ATI-2173 and Viread
ATI-2173 + Tenofovir disoproxil fumarate (Viread)
Drug: ATI-2173
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.
Other Name: Viread

Active Comparator: Placebo and Viread
ATI-2173 Placebo + Tenofovir disoproxil fumarate
Drug: Viread
Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.
Other Name: tenofovir disoproxil fumarate




Primary Outcome Measures :
  1. The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE) [ Time Frame: Through study completion, an average of 1 year ]
  2. The percentage of subjects who experienced at least one treatment emergent serious AE (SAE). [ Time Frame: Through study completion, an average of 1 year ]
  3. Percentage of subjects who experienced a treatment-emergent dose limiting toxicity (DLT) [ Time Frame: Through study completion, an average of 1 year ]
  4. 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 ]
  5. Percentage of subjects who discontinued study drug due to a TEAE [ Time Frame: Through study completion, an average of 1 year ]
  6. Alanine aminotransferase and aspartate aminotransferase levels versus time [ Time Frame: Through study completion, an average of 1 year ]
  7. Time to HBV viral load relapse in HBV-infected subjects [ Time Frame: Through study completion, an average of 1 year ]
  8. The reduction of HDV RNA on-treatment for HBV/HDV coinfected subjects [ Time Frame: Through study completion, an average of 1 year ]

Secondary Outcome Measures :
  1. TE(max, HBV) up to Day 90 and through end of study [ Time Frame: Through study completion, an average of 1 year ]
  2. AUEC(HBV) up to Day 90 and through end of study [ Time Frame: Through study completion, an average of 1 year ]
  3. TE(max, HDV) up to Day 90 and through end of study [ Time Frame: Through study completion, an average of 1 year ]
  4. AUEC(HDV) up to Day 90 and through end of study [ Time Frame: Through study completion, an average of 1 year ]
  5. Baseline-adjusted maximal reduction in HBV DNA viral load (Emax,HBV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects [ Time Frame: Through study completion at 6 months follow up ]
  6. Baseline-adjusted maximal reduction in HDV RNA viral load (Emax,HDV) through 6 months after end of treatment following ATI-2173 + tenofovir for 90 days in HBV/HDV coinfected subjects [ Time Frame: Through study completion at 6 months follow up ]
  7. Cmax of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  8. Tmax of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  9. Ctrough of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  10. Ctau of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  11. AUC0-24 of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  12. T1/2 of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  13. RAC(Cmax) of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  14. RAC(AUC) of ATI-2173, clevudine and M1 in plasma [ Time Frame: Through Day 120 ]
  15. Correlation between individual Day 90 clevudine and tenofovir Cmin and Emax,HBV or Emax, HDV of viral load [ Time Frame: Through Day 90 ]
  16. Proportion of subjects with HBV SVR6 by treatment arm [ Time Frame: Through study completion, an average of 1 year ]
  17. Proportion of subjects with HDV SVR6 by treatment arm (HBV/HDV coinfected subjects only) [ Time Frame: Through study completion, an average of 1 year ]
  18. Proportion of subjects by treatment arm with HBV SVR12, SVR18, and SVR24 [ Time Frame: Through study completion, an average of 1 year ]
  19. 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 ]
  20. Proportion of subjects by treatment arm with on-treatment ALT flares [ Time Frame: Through Day 90 ]
  21. 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 ]
  22. HBV DNA slope off-treatment [ Time Frame: Through end of study, an average of 1 year ]
  23. 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 ]
  24. HBV pgRNA at end of treatment by treatment arm [ Time Frame: Through Day 90 ]
  25. 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 ]
  26. 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 ]
  27. 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 ]
  28. 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 ]
  29. 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 ]
  30. Reduction from baseline in HBsAg, HBV pgRNA, and HBcrAg following ATI-2173 + tenofovir for 90 days in HBV-infected and in HBV/HDV coinfected subjects [ Time Frame: Through end of study, an average of 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. 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 and B 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

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 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 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 treatment for HBV or HDV, including nucleoside therapy, other than treatment by tenofovir or interferon alpha

    SUBJECTS WITH CHRONIC HBV:

  26. Positive screening results to HDV tests

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04847440


Locations
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Moldova, Republic of
Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit Recruiting
Chisinau, Republic Of Moldova, Moldova, Republic of
Contact: Andrei Colesnic    +37379689636    andrei.colesnic@arensia-em.com   
Principal Investigator: Alina Jucov         
Ukraine
Medical Center of Limited Liability Company "Harmoniya krasy" Recruiting
Kyiv, Ukraine
Contact: Valeriia Shtepa    380669411231    valeriia.shtepa@arensia-em.com   
Principal Investigator: Ihor Anastasiiy         
Sponsors and Collaborators
Antios Therapeutics, Inc
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Responsible Party: Antios Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT04847440    
Other Study ID Numbers: ANTT201
First Posted: April 19, 2021    Key Record Dates
Last Update Posted: May 26, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coinfection
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Virus Diseases
Herpesviridae Infections
Hepatitis D
Hepatitis
Infection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Parasitic Diseases
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents