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Hepatitis B, ChronicPhase 2NCT04847440

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

A Phase 2 study testing ATI-2173, Viread and AB-729 in people with Hepatitis B, Chronic and Hepatitis D, run by Antios Therapeutics, Inc at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatitis B, Chronic, Hepatitis D
What is being tested?
ATI-2173, Viread and AB-729
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesin 2 countries
Study dates
30 Mar 2021to 1 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • 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

Who cannot join

  • 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
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  • 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
  • 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)

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Moldova1 site
  • Republican Clinical Hospital "Timofei Mosneaga" Arensia EM Unit

    Chisinau, Republic of Moldova

Other trials in Moldova

Ukraine1 site
  • Medical Center of Limited Liability Company "Harmoniya krasy"

    Kyiv

Other trials in Ukraine

About this study

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

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.

Being tested
ATI-2173, Viread, AB-729
Medical subject headings
Hepatitis B, Chronic, Hepatitis D

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATI-2173Drug

    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.

  • VireadDrug

    Also called tenofovir disoproxil fumarate

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

  • AB-729Drug

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

Study groups in NCT04847440
Study groupRoleWhat they receive
ATI-2173 and VireadExperimentalATI-2173 + Tenofovir disoproxil fumarate (Viread)
Receives: Drug: ATI-2173
Placebo and VireadActive comparatorATI-2173 Placebo + Tenofovir disoproxil fumarate
Receives: Drug: Viread
ATI-2173, Viread and AB-729ExperimentalATI-2173 + Tenofovir disoproxil fumarate (Viread) + AB-729
Receives: Drug: AB-729
Placebo, Viread and AB-729 PlaceboActive comparatorATI-2173 Placebo + Tenofovir disoproxil fumarate (Viread) + AB-729 Placebo
Receives: Drug: Viread

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Through study completion, an average of 1 year

  2. The percentage of subjects who experienced at least one treatment emergent serious AE (SAE).

    Measured: Through study completion, an average of 1 year

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

    Measured: 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

    Measured: Through study completion, an average of 1 year

  5. Percentage of subjects who discontinued study drug due to a TEAE

    Measured: Through study completion, an average of 1 year

  6. Alanine aminotransferase and aspartate aminotransferase levels versus time

    Measured: Through study completion, an average of 1 year

  7. Time to HBV viral load relapse in HBV-infected subjects

    Measured: Through study completion, an average of 1 year

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

    Measured: Through study completion, an average of 1 year

Secondary outcomes (33)
  1. TE(max, HBV) up to Day 90 and through end of study with or without AB-729 or placebo + tenofovir

    Measured: Through study completion, an average of 1 year

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

    Measured: Through study completion, an average of 1 year

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

    Measured: Through study completion, an average of 1 year

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

    Measured: 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 (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects

    Measured: 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 or placebo + tenofovir for 90 days in HBV/HDV coinfected subjects

    Measured: Through study completion at 6 months follow up

  7. Cmax of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  8. Tmax of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  9. Ctrough of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  10. Ctau of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  11. AUC0-24 of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  12. T1/2 of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  13. RAC(Cmax) of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  14. RAC(AUC) of ATI-2173, clevudine, tenofovir and M1 in plasma

    Measured: Through Day 120

  15. Correlation between individual Day 90 clevudine and tenofovir Cmin and Emax,HBV or Emax, HDV of viral load

    Measured: Through Day 90

  16. Proportion of subjects with HBV SVR6 by treatment arm

    Measured: Through study completion, an average of 1 year

  17. Proportion of subjects with HDV SVR6 by treatment arm (HBV/HDV coinfected subjects only)

    Measured: Through study completion, an average of 1 year

  18. Proportion of subjects by treatment arm with HBV SVR12, SVR18, and SVR24

    Measured: 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)

    Measured: Through study completion, an average of 1 year

  20. Proportion of subjects by treatment arm with on-treatment ALT flares

    Measured: Through Day 90

  21. Proportion of subjects by treatment arm with off-treatment ALT flares, with no on-treatment ALT flares by treatment arm

    Measured: From Day 90 through end of study, an average of 1 year

  22. HBV DNA slope off-treatment

    Measured: 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

    Measured: Through end of study, an average of 1 year

  24. HBV pgRNA at end of treatment by treatment arm

    Measured: Through Day 90

  25. Effect on HBsAg in subjects who reach HBV SVR6 as measured by percentage of subjects by validated assay

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: Through end of study, an average of 1 year

  30. Change from baseline in HBsAg, HBV pgRNA, and HBcrAg at end of treatment and SVR6 in HBV-infected and in HBV/HDV coinfected subjects by treatment arm

    Measured: Through end of study, an average of 1 year

  31. Reduction from baseline in HBsAg, HBV pgRNA, and HBcrAg following ATI-2173 + tenofovir (with or without AB-729) or placebo + tenofovir for 90 days in HBV-infected and HBV/HDV coinfected subjects

    Measured: Through end of study, an average of 1 year

  32. Correlation between individual time to viral load relapse and Day 90 clevudine and/or tenofovir Cmin and AUC

    Measured: Through Day 90

  33. Correlation between SVR6 and Day 90 clevudine and/or tenofovir Cmin and AUC

    Measured: Through Day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2021
  2. Study start30 Mar 2021
  3. Primary completion1 Sep 2022
  4. Study completion1 Sep 2022

Why it stopped: Terminated by the Sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04847440
Sponsor's protocol ID
ANTT201
Status last verified
Nov 2022
First submitted
6 Apr 2021
Last updated
18 Nov 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ATI-2173, Viread and AB-729 in people with Hepatitis B, Chronic and Hepatitis D, run by Antios Therapeutics, Inc at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Moldova, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Terminated by the Sponsor). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE) (time frame: Through study completion, an average of 1 year). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2022.

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