Study of GS-4321 in Healthy Participants and Participants With Chronic Hepatitis Delta Virus

NCT07096193 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GS-US-567-69682025-522729-36
• Study Type: interventional
• Target: 107
• Locations: 5 countries
• Sites: 15

Brief Summary

The goals of this clinical study are to first learn more about safety and dosing of the study drug GS-4321 in healthy participants. The study will then learn about the safety and effectiveness of GS-4321 in participants with chronic hepatitis delta (CHD). The primary objective of Phase 1 of this study is to evaluate the safety, tolerability and Pharmacokinetics (PK) of the escalating single doses of GS-4321 administered in healthy participants. The primary objective of Phase 2 of this study is to evaluate the efficacy and safety of the multiple escalating doses of GS-4321 in participants with CHD.

Conditions

Chronic Hepatitis Delta

Outcome Measures

Primary Outcomes (9)

• Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events

  Phase 1: First dose up to 44 weeks; Phase 2: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up

• Phase 1 and 2: Percentage of Participants With Treatment-emergent Serious Adverse Events

  Phase 1: First dose up to 44 weeks; Phase 2: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up

• Phase 1 and 2: Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities

  Phase 1: First dose up to 44 weeks; Phase 2: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up

• Phase 1: Serum Pharmacokinetic (PK) parameter; AUClast of GS-4321

  AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.

  First dose up to 24 Weeks

• Phase 1: Serum PK Parameter: AUCinf

  AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time.

  First dose up to 24 Weeks

• Phase 1: Serum PK Parameter: Cmax

  Cmax is defined as the maximum observed concentration of drug.

  First dose up to 24 Weeks

• Phase 1: Serum PK Parameter: Tmax

  Tmax is defined as the time (observed time point) of Cmax.

  First dose up to 24 Weeks

• Phase 1: Serum PK Parameter: t1/2

  First dose up to 24 Weeks

• Phase 2: Proportion of Participants with Combined Response

  Combined Response is defined as undetectable hepatitis delta virus (HDV) RNA or ≥ 2 log10 decrease in HDV RNA from baseline and normal alanine aminotransferase (ALT) normalization (ALT \< upper limit of normal (ULN) at week 24).

  Up to 96 Weeks

Secondary Outcomes (13)

• Phase 1: Proportion of Participants who Develop Antidrug Antibody (ADAs) After Administration of a Single Dose of GS-4321 and ADA Titer Characterization

  First dose up to 24 Weeks

• Phase 2: Serum PK Parameters AUCtau of GS-4321

  Up to 96 weeks

• Phase 2: Serum PK Parameters Cmax of GS-4321

  Up to 96 Weeks

• Phase 2: Serum PK Parameters Tmax of GS-4321

  Up to 96 Weeks

• Phase 2: Serum PK Parameters Ctrough of GS-4321

  Up to 96 Weeks

Study Arms (3)

Phase 1: GS-4321

EXPERIMENTAL

Participants will receive single escalating doses of GS-4321.

Drug: GS-4321

Phase 1: Placebo

PLACEBO COMPARATOR

Participants will receive placebo to match the single escalating doses of GS-4321

Drug: GS-4321 Placebo

Phase 2: GS-4321

EXPERIMENTAL

Participants will receive multiple escalating doses of GS-4321 up to 96 weeks.

Drug: GS-4321

Interventions

GS-4321 Placebo DRUG

Administered SC

Phase 1: Placebo

GS-4321 DRUG

Administered subcutaneous (SC) or intravenously IV

Phase 1: GS-4321

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (15)

Investigative Site

Anaheim, California, 92801, United States

RECRUITING

University of Maryland, Institute of Human Virology, Clinical Research Unit

Baltimore, Maryland, 21201, United States

RECRUITING

The New York-Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba"

Chinsinau, 2004, Moldova

RECRUITING

PMSI Clinical Republican Hospital "Timofei Mosneaga"

Chisinau, MD-2025, Moldova

RECRUITING

Institutul National De Boli Infectioase Prof. Dr. Matei Bals

Bucharest, 021105, Romania

RECRUITING

Fundatia Dr. Victor Babes

Bucharest, 030303, Romania

RECRUITING

Infectious Diseases Institutul National De Boli Infectioase Prof. Matei Bals

Bucharest, 21105, Romania

RECRUITING

Gastromedica S.R.L.

Iași, 700506, Romania

RECRUITING

Korea University Ansan Hospital

Ansan-si, 425-707, South Korea

RECRUITING

The Catholic University of Korea Bucheon St. Mary's Hospital

Bucheon-si, 14647, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Samsung Medical Center

Seoul, 135-710, South Korea

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

RECRUITING

Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hepatitis D, Chronic

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: July 31, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

RO (4); MO (2); US (3); TW (2); KR (4)