GS-4321 for healthy volunteers and people with chronic hepatitis delta

Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-4321 in Healthy Participants and Participants With Chronic Hepatitis Delta

This study tries to find safe doses of GS-4321 in healthy volunteers and see if the drug is safe and can lower hepatitis delta virus levels in people with chronic hepatitis delta.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 107 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Gilead Sciences (industry)
• Locations: 15 sites (Anaheim, California and 14 other locations)
• Trial ID: NCT07096193 on ClinicalTrials.gov

What this trial studies

The trial is a Phase 1/2, first testing single ascending doses of GS-4321 in healthy adults to characterize safety, tolerability, and pharmacokinetics. In Phase 2, people with chronic hepatitis delta receive multiple escalating doses to measure safety and antiviral activity, with some participants randomized to placebo. Participants with HBV coinfection must remain on standard HBV antiviral therapy, and non‑decompensated liver disease is required for enrollment. Clinical and laboratory monitoring, including HDV RNA and liver tests, will be used to judge tolerability and antiviral effect across dose levels.

Who should consider this trial

Good fit: Ideal candidates are adults with chronic hepatitis delta for at least six months with HDV RNA >100 IU/mL who are on HBV antiviral therapy and have non‑decompensated liver disease, while Phase 1 includes healthy adults with BMI ≤30 kg/m2.

Not a fit: People with decompensated cirrhosis, uncontrolled medical conditions, or who are not on required HBV antiviral therapy are unlikely to benefit from this early-phase study.

Why it matters

Potential benefit: If successful, GS-4321 could lower HDV viral levels and help slow liver disease progression in people with chronic hepatitis delta.

How similar studies have performed: Other antiviral approaches for HDV such as bulevirtide and lonafarnib have shown positive results in prior trials, but GS-4321 is a novel agent being tested in early-phase studies.

Eligibility criteria

Key Inclusion Criteria:

Part A:

* Participants assigned male or female at birth who are of childbearing potential and engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
* Have a body mass index (BMI) of ≤ 30.0 kg/m2 at screening and at admission.

Part B:

* Participants assigned male or female at birth who are of childbearing potential and engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
* Chronic hepatitis delta (CHD) for ≥ 6 months prior to screening, documented by prior medical history.
* Must be receiving a commercially available entecavir, TAF, or TDF for the treatment of hepatitis B virus (HBV) infection at or prior to enrollment. Coformulation as part of a fixed-dose combination for the treatment of HIV is permitted.
* Non-cirrhotic or compensated cirrhosis.
* Hepatitis delta virus ribonucleic acid (HDV RNA ) \> 100 IU/mL at screening.
* Alanine aminotransferase (ALT) level \> 1 × Upper limit of normal (ULN), but \< 10 × ULN at screening.

Key Exclusion Criteria:

Part A:

* Positive serum or urine pregnancy test.
* Participants with plans to breastfeed during the study period.

Part B:

* Positive serum or urine pregnancy test.
* Participants with plans to breastfeed during the study period.
* Current or previous clinically decompensated liver disease, including coagulopathy, hepatic encephalopathy, and esophageal varices hemorrhage due to HDV or HBV.
* Child-Turcotte-Pugh (CTP)-B or -C or a CTP score of ≥ 7.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Anaheim, California and 14 other locations

• Investigative Site — Anaheim, California, United States (RECRUITING)
• University of Maryland, Institute of Human Virology, Clinical Research Unit — Baltimore, Maryland, United States (RECRUITING)
• The New York-Presbyterian Hospital — New York, New York, United States (RECRUITING)
• IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba" — Chinsinau, Moldova (RECRUITING)
• PMSI Clinical Republican Hospital "Timofei Mosneaga" — Chisinau, Moldova (RECRUITING)
• Institutul National De Boli Infectioase Prof. Dr. Matei Bals — Bucharest, Romania (RECRUITING)
• Fundatia Dr. Victor Babes — Bucharest, Romania (RECRUITING)
• Infectious Diseases Institutul National De Boli Infectioase Prof. Matei Bals — Bucharest, Romania (RECRUITING)
• Gastromedica S.R.L. — Iași, Romania (RECRUITING)
• Korea University Ansan Hospital — Ansan-si, South Korea (RECRUITING)
• The Catholic University of Korea Bucheon St. Mary's Hospital — Bucheon-si, South Korea (RECRUITING)
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul, South Korea (RECRUITING)
• Samsung Medical Center — Seoul, South Korea (RECRUITING)
• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan (RECRUITING)
• Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Gilead Clinical Study Information Center

Conditions: Chronic Hepatitis Delta