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About
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.
Enrollment
Sex
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Volunteers
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:
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:
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:
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)
Primary purpose
Allocation
Interventional model
Masking
40 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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