A Phase 1 Double-Blinded Study for Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ATI-2173 in Healthy Subjects and Subjects With Chronic Hepatitis B Virus Infection

Antios Therapeutics, Inc3 个研究点分布在 3 个国家目标入组 88 人开始时间: 2020年2月5日最近更新: 2021年8月19日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Antios Therapeutics, Inc
入组人数: 88
试验地点: 3
主要终点: The percentage of subjects who experienced at least one treatment emergent serious AE (SAE).

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a double-blinded, randomized, placebo-controlled study of safety, tolerability, pharmacokinetics, and antiviral activity in both healthy volunteers and volunteers with chronic hepatitis B virus infection. Healthy volunteers will be administered either a single oral dose or multiple oral doses of ATI-2173 and assessed for safety and tolerability including blood tests to show how the body metabolizes and eliminates the investigational drug. Volunteers with a diagnosis of chronic hepatitis B virus infection will be administered multiple oral doses of ATI-2173 and assessed for safety and tolerability including blood tests to show how the body metabolizes and eliminates the investigational drug as well as how the drug effects the virus infection.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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 1 of the following criteria:
•Is of childbearing potential and agrees to use an accepted contraceptive method. Acceptable method of contraception include:
•Abstinence from heterosexual intercourse from at least 28 days prior to 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
•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 30 days 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 Or
•Male partner has had a vasectomy less than 6 months prior to dosing, and agrees to use an additional acceptable contraceptive method 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 Or
•Is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (i.e. at least 1 year without menses without an alternative medical condition prior to the first study drug administration and follicle-stimulating hormone levels ≥ 40 mIU/mL at screening)
•If male, meets 1 of the following criteria:
•Is able to procreate and agrees to use 1 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 1 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 (i.e. has undergone a vasectomy at least 180 days prior to the first study drug administration)
•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. An ex smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
•Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by an investigator
•Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator
•Healthy subjects (Phase 1a):
•Male or female, aged at least 18 years but not older than 55 years
•Body mass index (BMI) within 18.0 kg/m2 to 32.0 kg/m2, inclusive
•HBV-infected subjects (Phase 1b):
•Male or female, aged at least 18 years but not older than 65 years
•BMI within 18.0 kg/m2 to 35.0 kg/m2, inclusive
•Serum HBsAg positive at screening and at least 6 months prior to screening
•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 prior to the first study drug administration

排除标准

•All subjects:
•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 or any related products (including excipients of the formulations) 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 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
•Inclusion in a previous cohort for this clinical study
•Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration
•Active illicit drug use including, but not limited to, cocaine, heroin and methamphetamine (the use of cannabinoid is acceptable)
•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
•Healthy subjects (Phase 1a):
•Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
•Any clinically significant illness in the 28 days prior to the first study drug administration
•Presence or history of clinically significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability
•Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus tests
•Use of any prescription drugs including amiodarone (with the exception of hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the participant as healthy
•HBV-infected subjects (Phase 1b):
•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 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
•Medical history or known presence of hepatocellular carcinoma
•Previous treatment for hepatitis B virus, including nucleoside therapy
•Acute infection or any other clinically significant illness within 14 days of randomization
•History of organ transplantation
•Uncontrolled hypertension
•Positive screening results to HIV Ag/Ab combo, hepatitis C virus or hepatitis D virus tests

研究组 & 干预措施

ATI-2173

Experimental

干预措施: ATI-2173 (Drug)

ATI-2173 Placebo

Placebo Comparator

干预措施: ATI-2173 Placebo (Drug)