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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Mar 2026 → ongoing

Decision date (initial)

2026-02-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2025-522729-36-00

ClinicalTrials.gov

NCT07096193

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

Part A Objectives:
To evaluate the safety and tolerability of escalating single doses of GS-4321 administered in healthy participants.
To evaluate the pharmacokinetics (PK) of a single dose of GS-4321 following subcutaneous (SC) and intravenous (IV) administration.
Part B Objectives:
To evaluate the efficacy of GS-4321 in participants with chronic hepatitis delta infection (CHD)
To evaluate the safety and tolerability of escalating multiple doses of GS-4321 administered in participants with CHD

Secondary objectives 2

1. Part A Objectives: To evaluate the immunogenicity of GS-4321
2. Part B Objectives: To evaluate the PK of multiple doses of GS-4321 following SC administration. To evaluate the efficacy of GS-4321 in participants with CHD • To evaluate the immunogenicity of GS-4321. To evaluate the emergence of viral resistance to GS-4321 during treatment

Conditions and MedDRA coding

Chronic Hepatitis Delta.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 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.
3. 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.
4. Part A: Have a body mass index (BMI) of ≤ 30.0 kg/m2 at screening and at admission.
5. Part B: CHD for ≥ 6 months prior to screening, documented by prior medical history.
6. 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.
7. 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
8. Part B: HDV RNA > 500 IU/mL at screening.
9. 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).
10. 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.
11. 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.

Exclusion criteria 2

1. Part A : Positive serum or urine pregnancy test. Participants with plans to breastfeed during the study period.
2. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A Endpoints : Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and graded laboratory abnormalities. Serum PK parameters AUClast, AUCinf, Cmax, Tmax, and t1/2 of GS-4321, as applicable. Additional parameters may be evaluated as applicable.
2. Part B Endpoints: Proportion 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). Incidences of TEAEs, SAEs, and graded laboratory abnormalities

Secondary endpoints 10

1. Part A Endpoints: Proportion of participants who develop antidrug antibodies (ADAs) after administration of a single dose of GS-4321 and ADA titer characterization
2. Part B Endpoints: Serum PK parameters AUCtau, Cmax, Tmax, and Ctrough of GS-4321, as applicable. Additional parameters may be evaluated, as applicable.
3. 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
4. Part B Endpoints: Change from baseline in HDV RNA at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
5. 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
6. 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
7. Part B Endpoints: Change in liver stiffness by elastography from baseline at Weeks 24, 48, and 96
8. Part B Endpoints: Proportion of participants with normal ALT at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
9. Part B Endpoints: Proportion of participants who develop ADAs after administration of multiple doses of GS-4321 and ADA titer characterization
10. Part B Endpoints: Characterize if emergent variants are associated with reduced susceptibility to GS-4321 in vitro and virologic failure in participants with CHD

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 12

Locations

4 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications