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

NCT05238844 | Terminated Phase 2

• 1 other identifier: ANTT202
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (7)

• The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE)

  Through study completion, an average of 1 year

• The percentage of subjects who experienced at least 1 treatment-emergent serious adverse event (TE SAE)

  Through study completion, an average of 1 year

• The percentage of subjects who experienced a treatment-emergent dose-limiting toxicity (TE DLT)

  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

  Through study completion, an average of 1 year

• The percentage of subjects who discontinued the study drug due to a TEAE

  Through study completion, an average of 1 year

• Alanine aminotransferase and aspartate aminotransferase levels versus time

  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

  Through study completion, an average of 1 year, which is 6 months after end of treatment

Secondary Outcomes (43)

• 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

  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

  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

  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

  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

  Through study completion, an average of 1 year

Study Arms (2)

ATI-2173 25mg, Vebicorvir 300mg and Tenofovir 300mg

EXPERIMENTAL

Subjects randomized to active arm will receive active 25mg ATI-2173 + active Vebicorvir 300mg + active Tenofovir 300mg

Drug: ATI-2173 25mg; Drug: Vebicorvir 300mg; Drug: Viread 300Mg Tablet

Tenofovir Disoproxil Fumarate

ACTIVE COMPARATOR

Subjects randomized to placebo arm will receive placebo 25mg ATI-2173 + placebo Vebicorvir 300mg + active Tenofovir 300mg

Drug: Viread 300Mg Tablet

Interventions

ATI-2173 25mg DRUG

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.

ATI-2173 25mg, Vebicorvir 300mg and Tenofovir 300mg

Vebicorvir 300mg DRUG

Vebicorvir (formerly ABI-H0731) is an orally administered, potent and selective small molecule inhibitor of the HBV core protein

ATI-2173 25mg, Vebicorvir 300mg and Tenofovir 300mg

Viread 300Mg Tablet DRUG

Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.

ATI-2173 25mg, Vebicorvir 300mg and Tenofovir 300mg; Tenofovir Disoproxil Fumarate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 non-hormonal intrauterine device, 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
• Use of a double-barrier method
• Male partner vasectomized at least 6 months prior to the first study drug administration 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 the subject engages in sexual relations, a barrier method (male or female condom) should be used to prevent the spread of HBV.
• If male, meets one of the following criteria:
• a) 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 c) Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 6 months prior to the first study drug administration). If the subject engages in sexual relations, a barrier method (male or female condom) should be used to prevent the spread of HBV.
• 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

You may not qualify if:

• 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 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 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

Sponsors & Collaborators

• Antios Therapeutics, Inc: lead

Study Sites (2)

Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit

Chisinau, Republic of Moldova, Moldova

Location

Medical Center of Limited Liability Company "Harmoniya krasy"

Kyiv, Ukraine

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Tenofovir; Tablets

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 14, 2022
• Study Start: April 11, 2022
• Primary Completion: May 25, 2022
• Study Completion: May 25, 2022
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

UA (1); MO (1)