Chronic Hepatitis DeltaPhase 1/2NCT07096193
Study of GS-4321 in Healthy Participants and Participants With Chronic Hepatitis Delta Virus
A Phase 1/2 study testing GS-4321 in people with Chronic Hepatitis Delta, run by Gilead Sciences at 28 sites in 9 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 69 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis Delta
- What is being tested?
- GS-4321
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 28 sitesin 9 countries
- Study dates
- 31 Jul 2025to Jan 2030
- Phase
- Phase 1/2
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 69 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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 ) > 500 IU/mL at screening.
- Alanine aminotransferase (ALT) level > 1 × Upper limit of normal (ULN), but < 10 × ULN at screening.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
28 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
Gilead Clinical Study Information Center contact
28 sites in 9 countries
Turkey (Türkiye)6 sites, 6 recruiting
- Recruiting
Hacettepe University Faculty of Medicine Hospital Hacettepe Neighborhood
Ankara, 06430
- Recruiting
Ankara Bilkent City Hospital Oncology Hospital Universiteler Neighborhood
Ankara, 06800
- Recruiting
Ankara Bilkent City Hospital Universiteler Neighborhood, 1604th Street No: 9,
Ankara, 6800
- Recruiting
Dicle University Faculty of Medicine
Diyarbakrir, 21280
- Recruiting
Istabul University-Cerrahpasa Faculty of Medicine Hospital
Istanbul, 34000
- Recruiting
Koc University Medical Faculty Hospital
Istanbul, 34010
United States5 sites, 5 recruiting
- Recruiting
Investigative Site
Anaheim, California, 92801
- Recruiting
University of Maryland, Institute of Human Virology, Clinical Research Unit
Baltimore, Maryland, 21201
- Recruiting
University of California, San Diego - Altman Clinical and Translational Research Institute
La Jolla, California, 92093
- Recruiting
University of Louisville, Clinical Trials Unit
Louisville, Kentucky, 40202
- Recruiting
The New York-Presbyterian Hospital
New York, New York, 10021
Romania4 sites, 4 recruiting
- Recruiting
Institutul National De Boli Infectioase Prof. Dr. Matei Bals
Bucharest, 021105
- Recruiting
Fundatia Dr. Victor Babes
Bucharest, 030303
- Recruiting
Infectious Diseases Institutul National De Boli Infectioase Prof. Matei Bals
Bucharest, 21105
- Recruiting
Gastromedica S.R.L.
Iași, 700506
South Korea4 sites, 4 recruiting
- Recruiting
Korea University Ansan Hospital
Ansan-si, 425-707
- Recruiting
The Catholic University of Korea Bucheon St. Mary's Hospital
Bucheon-si, 14647
- Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
- Recruiting
Samsung Medical Center
Seoul, 135-710
Taiwan4 sites, 4 recruiting
- Recruiting
Ditmanson Medical Foundation Chia-Yi Christian Hospital
Chiayi City
- Recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
- Recruiting
Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
- Recruiting
National Taiwan University Hospital
Taipei, 100
Moldova2 sites, 2 recruiting
- Recruiting
IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba"
Chinsinau, 2004
- Recruiting
PMSI Clinical Republican Hospital "Timofei Mosneaga"
Chisinau, MD-2025
Bulgaria1 site, 1 recruiting
- Recruiting
University Multi-profile Hospital for Active Treatment "SofiaMed" 00D
Sofia, 1797
Germany1 site, 1 recruiting
- Recruiting
Medizinische Hochschule Hannover, Address: Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
Hanover, 30625
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, SC Gastroenterologia ed Epatologia
Milan, 882
About this study
Official title: 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
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
- Being tested
- GS-4321, GS-4321 Placebo
- Medical subject headings
- Hepatitis D, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-4321Drug
Administered subcutaneous (SC) or intravenously IV
GS-4321 PlaceboDrug
Administered SC
GS-4321Drug
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: GS-4321 | Experimental | Participants will receive single escalating doses of GS-4321. Receives: Drug: GS-4321 |
| Phase 1: Placebo | Placebo comparator | Participants will receive placebo to match the single escalating doses of GS-4321 Receives: Drug: GS-4321 Placebo |
| Phase 2: GS-4321 | Experimental | Participants will receive multiple escalating doses of GS-4321 up to 96 weeks. Receives: Drug: GS-4321 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events
Measured: 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
Measured: 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
Measured: 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; AUC of GS-4321
AUC is defined as the area under the concentration versus time curve
Measured: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: Cmax
Cmax is defined as the maximum observed concentration of drug.
Measured: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: Tmax
Tmax is defined as the time (observed time point) of Cmax.
Measured: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: t1/2
Measured: 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).
Measured: 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
ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .
Measured: First dose up to 24 Weeks
Phase 2: Serum PK Parameters AUC of GS-4321
Measured: Up to 96 weeks
Phase 2: Serum PK Parameters Cmax of GS-4321
Measured: Up to 96 Weeks
Phase 2: Serum PK Parameters Tmax of GS-4321
Measured: Up to 96 Weeks
Phase 2: Serum PK Parameters Ctrough of GS-4321
Measured: Up to 96 Weeks
Phase 2: Proportion of Participants With Undetectable HDV RNA or ≥ 2 log10 Decrease in HDV RNA From Baseline and normal ALT (ALT < ULN).
Measured: Weeks 4, 8, 12, 16, 20, 36, 48, 60, 72, 84, and 96
Phase 2: Change From Baseline in HDV RNA
Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
Phase 2: Proportion of Participants With Undetectable HDV RNA
Measured: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
Proportion of Participants With undetectable HDV RNA or ≥ 2 log10 Decrease in HDV From Baseline
Measured: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84 and 96
Phase 2: Change From Baseline in Liver Stiffness by Elastography
Measured: Weeks 24, 48, and 96
Phase 2: Proportion of Participants with normal ALT
Measured: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
Phase 2: Proportion of Participants who Develop ADAs After Administration of Multiple Doses of GS-4321 and ADA Titer Characterization
ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .
Measured: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up
Phase 2: Characterize if Emergent Variants are Associated With Reduced Susceptibility to GS-4321 in Vitro and Virologic Failure in Participants With CHD
Measured: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start31 Jul 2025
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis DeltaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07096193
- Sponsor's protocol ID
- GS-US-567-6968
- Other IDs
- 2025-522729-36, 2025
- Status last verified
- Aug 2026
- First submitted
- 24 Jul 2025
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No