GS-4321 for Chronic hepatitis delta

Inclusion criteria

• {"criterion_text":"- Part A: Participants 18 years of age to < 70 years at screening, able to understand and give written informed consent and comply with treatment and follow-up.\n- Part B: Participants 18 years of age to < 70 years at screening, able to understand and give written informed consent and comply with treatment and follow-up.\n- 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.\n- 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.\n- Part A: Must, in the opinion of the investigator, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, and screening laboratory evaluations.\n- Part A: Have a body mass index (BMI) of ≤ 30.0 kg/m2 at screening and at admission.\n- Part B: CHD for ≥ 6 months prior to screening, documented by prior medical history.\n- Part B: Must be receiving commercially available entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate at or prior to enrollment. Coformulation as part of a fixed-dose combination for the treatment of HIV is permitted.\n- Part B: Noncirrhotic or compensated cirrhotic liver disease as defined below: 1. Noncirrhotic as defined by liver stiffness (as measured by elastography, eg, FibroScan®) < 12.5 kPa within the 6 months prior to or at screening 2. Compensated cirrhotic as defined by meeting all criteria below: a. Liver stiffness (as measured by elastography, eg, FibroScan) ≥ 12.5 within the 6 months prior to or at screening b. Child-Turcotte-Pugh (CTP) score of < 7 at screening\n- Part B: HDV RNA > 500 IU/mL at screening.\n- Part B: ALT level > 1 × ULN, but < 10 × ULN at screening (Cohorts B1, B2, and B3) or ALT < 10 × ULN at screening (Cohort B4, ≤ ULN, with sponsor approval)."}

Exclusion criteria

• {"criterion_text":"- Part A : Positive serum or urine pregnancy test. Participants with plans to breastfeed during the study period.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Part A Endpoints :\tIncidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and graded laboratory abnormalities.\tSerum PK parameters AUClast, AUCinf, Cmax, Tmax, and t1/2 of GS-4321, as applicable. Additional parameters may be evaluated as applicable.","definition_or_measurement_approach":"Incidence of TEAEs/SAEs and graded laboratory abnormalities assessed during treatment; serum pharmacokinetic parameters measured (AUClast, AUCinf, Cmax, Tmax, t1/2) as applicable."}
• {"endpoint_text":"- Part B Endpoints:\tProportion of participants with combined response (defined as undetectable hepatitis delta virus [HDV] RNA or ≥ 2 log10 decrease in HDV RNA from baseline and normal alanine aminotransferase [ALT] (ALT < upper limit of normal [ULN]) at Week 24).\tIncidences of TEAEs, SAEs, and graded laboratory abnormalities","definition_or_measurement_approach":"Combined response defined as undetectable HDV RNA OR ≥2 log10 decrease in HDV RNA from baseline AND ALT < ULN at Week 24; incidence of TEAEs/SAEs and graded laboratory abnormalities monitored."}

Secondary endpoints

• {"endpoint_text":"- Part A Endpoints:\tProportion of participants who develop antidrug antibodies (ADAs) after administration of a single dose of GS-4321 and ADA titer characterization","definition_or_measurement_approach":"Proportion developing ADAs after single dose; ADA titers characterized."}
• {"endpoint_text":"- Part B Endpoints:\tSerum PK parameters AUCtau, Cmax, Tmax, and Ctrough of GS-4321, as applicable. Additional parameters may be evaluated, as applicable.","definition_or_measurement_approach":"Serum PK parameters (AUCtau, Cmax, Tmax, Ctrough) measured for GS-4321 following dosing."}
• {"endpoint_text":"- Part B Endpoints: Proportion of participants with undetectable HDV RNA or ≥ 2 log10 decrease in HDV RNA from baseline and normal ALT (ALT < ULN) at Weeks 4, 8, 12, 16, 20, 36, 48, 60, 72, 84, and 96","definition_or_measurement_approach":"Proportion meeting combined virologic and ALT response at specified weeks (undetectable HDV RNA or ≥2 log10 decrease from baseline AND ALT < ULN)."}
• {"endpoint_text":"- Part B Endpoints: Change from baseline in HDV RNA at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96","definition_or_measurement_approach":"Change from baseline in HDV RNA measured at listed timepoints."}
• {"endpoint_text":"- Part B Endpoints: Proportion of participants with undetectable HDV RNA at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96","definition_or_measurement_approach":"Proportion with undetectable HDV RNA at listed timepoints."}
• {"endpoint_text":"- Part B Endpoints: Proportion of participants with undetectable HDV RNA or ≥ 2 log10 decrease in HDV RNA from baseline at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96","definition_or_measurement_approach":"Proportion meeting virologic reduction criteria (undetectable or ≥2 log10 decrease) at listed weeks."}
• {"endpoint_text":"- Part B Endpoints: Change in liver stiffness by elastography from baseline at Weeks 24, 48, and 96","definition_or_measurement_approach":"Change in liver stiffness measured by elastography (e.g., FibroScan) at Weeks 24, 48, 96."}
• {"endpoint_text":"- Part B Endpoints: Proportion of participants with normal ALT at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96","definition_or_measurement_approach":"Proportion with ALT < ULN at listed weeks."}
• {"endpoint_text":"- Part B Endpoints: Proportion of participants who develop ADAs after administration of multiple doses of GS-4321 and ADA titer characterization","definition_or_measurement_approach":"Proportion developing ADAs after multiple doses; ADA titers characterized."}
• {"endpoint_text":"- Part B Endpoints: Characterize if emergent variants are associated with reduced susceptibility to GS-4321 in vitro and virologic failure in participants with CHD","definition_or_measurement_approach":"Genotypic/phenotypic characterization of emergent viral variants for reduced susceptibility and correlation with virologic failure."}

Bulgaria

Earliest CTIS Part Ii Submission Date

14-01-2026

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

09-12-2025

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

64

Number Of Sites

1

Number Of Participants

2

Romania

Earliest CTIS Part Ii Submission Date

15-01-2026

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

32

Number Of Sites

4

Number Of Participants

25

Germany

Earliest CTIS Part Ii Submission Date

09-01-2026

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

60

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Gilead Sciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Biomarker Analysis in human serum

Name

PPD Development LP

Responsibilities

Investigator selection; other site support (codes present in sponsor duties)

Name

Labcorp Drug Development Inc.

Responsibilities

Biomarker/sample analysis support (specific duties not detailed)

Name

Fisher Clinical Services Inc.

Responsibilities

Distribution

Name

Syneos Health Inc.

Responsibilities

FSP Site Contract Negotiations

Name

Medidata Solutions Inc.

Responsibilities

Data capture/technical platform support (responsibility code present)

Third parties

• {"country":"United States","full_name":"Immunologix","duties_or_roles":"Bioanalytical Analysis in human serum","organisation_type":"Health care"}
• {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"Biomarker Analysis in human serum","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"ARENSIA Exploratory Medicine GmbH","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Romania","full_name":"Arensia Exploratory Medicine S.R.L.","duties_or_roles":"codes: 12, 2, 5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Biomarker Analysis in human serum","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Investigator selection","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"FSP Site Contract Negotiations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Drug Development Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Seq-it GmbH & Co. KG","duties_or_roles":"Virology assessments- in human plasma (Genotyping)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"Biomarker Analysis in human serum","organisation_type":"Pharmaceutical company"}