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

NCT04847440 | Terminated Phase 2

• 1 other identifier: ANTT201
• Study Type: interventional
• Target: 40
• 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 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.

Conditions

Hepatitis B, Chronic; Hepatitis D

Outcome Measures

Primary Outcomes (8)

• 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 one treatment emergent serious AE (SAE).

  Through study completion, an average of 1 year

• Percentage of subjects who experienced a treatment-emergent dose limiting toxicity (DLT)

  Through study completion, an average of 1 year

• Percentage of subjects who experienced at least one treatment emergent Grade 1, 2, 3, 4 or 5 laboratory abnormality

  Through study completion, an average of 1 year

• Percentage of subjects who discontinued 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

  Through study completion, an average of 1 year

• The reduction of HDV RNA on-treatment for HBV/HDV coinfected subjects

  Through study completion, an average of 1 year

Secondary Outcomes (33)

• TE(max, HBV) up to Day 90 and through end of study with or without AB-729 or placebo + tenofovir

  Through study completion, an average of 1 year

• AUEC(HBV) up to Day 90 and through end of study with or without AB-729 of placebo + tenofovir

  Through study completion, an average of 1 year

• TE(max, HDV) up to Day 90 and through end of study

  Through study completion, an average of 1 year

• AUEC(HDV) up to Day 90 and through end of study

  Through study completion, an average of 1 year

• 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

  Through study completion at 6 months follow up

Study Arms (4)

ATI-2173 and Viread

EXPERIMENTAL

ATI-2173 + Tenofovir disoproxil fumarate (Viread)

Drug: ATI-2173

Placebo and Viread

ACTIVE COMPARATOR

ATI-2173 Placebo + Tenofovir disoproxil fumarate

Drug: Viread

ATI-2173, Viread and AB-729

EXPERIMENTAL

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

Drug: AB-729

Placebo, Viread and AB-729 Placebo

ACTIVE COMPARATOR

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

Drug: Viread

Interventions

ATI-2173 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. Viread is a nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus.

ATI-2173 and Viread

Viread DRUG

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

Also known as: tenofovir disoproxil fumarate

Placebo and Viread; Placebo, Viread and AB-729 Placebo

AB-729 DRUG

AB-729 is a potent, selective, subcutaneously administered, N-acetylgalactosamine (Ga1NAc)-conjugated small interfering ribonucleic acid (siRNA) inhibitor of HBV

ATI-2173, Viread and AB-729

Eligibility Criteria

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

You may qualify if:

• 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)

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 (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

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; Hepatitis D

Interventions

Tenofovir

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; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: April 6, 2021
• First Posted: April 19, 2021
• Study Start: March 30, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: November 18, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); UA (1)