A Phase 1/2 interventional study of GS-4321 and GS-4321 Placebo in Chronic Hepatitis Delta, sponsored by Gilead Sciences. Recruiting at 28 sites in 9 countries. Open to participants aged 18 Years to 69 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-27.
Sponsored by Gilead Sciences · Phase 1/2, Interventional, and Treatment
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.
43 studies on the registry are indexed under Hepatitis D, Chronic; 9 are open to participants now.
This study's planned enrollment of 200 is above the median of 46 across 30 interventional studies indexed under Hepatitis D, Chronic.
Browse Hepatitis D, Chronic studies →Gilead Sciences is the lead sponsor of 692 studies on the registry; 26 are open to participants now.
Of its 261 completed or terminated interventional studies of FDA-regulated products, 251 (96%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Part A:
Part B:
Key Exclusion Criteria:
Part A:
Part B:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive single escalating doses of GS-4321.
Drug: GS-4321
Participants will receive placebo to match the single escalating doses of GS-4321
Drug: GS-4321 Placebo
Participants will receive multiple escalating doses of GS-4321 up to 96 weeks.
Drug: GS-4321
Administered subcutaneous (SC) or intravenously IV
Administered SC
Administered SC
Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: Cmax
Cmax is defined as the maximum observed concentration of drug.
Time frame: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: Tmax
Tmax is defined as the time (observed time point) of Cmax.
Time frame: First dose up to 24 Weeks
Phase 1: Serum PK Parameter: t1/2
Time frame: 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).
Time frame: Up to 96 Weeks
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 .
Time frame: First dose up to 24 Weeks
Phase 2: Serum PK Parameters AUC of GS-4321
Time frame: Up to 96 weeks
Phase 2: Serum PK Parameters Cmax of GS-4321
Time frame: Up to 96 Weeks
Phase 2: Serum PK Parameters Tmax of GS-4321
Time frame: Up to 96 Weeks
Phase 2: Serum PK Parameters Ctrough of GS-4321
Time frame: 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).
Time frame: Weeks 4, 8, 12, 16, 20, 36, 48, 60, 72, 84, and 96
Phase 2: Change From Baseline in HDV RNA
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96
Phase 2: Proportion of Participants With Undetectable HDV RNA
Time frame: 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
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84 and 96
Phase 2: Change From Baseline in Liver Stiffness by Elastography
Time frame: Weeks 24, 48, and 96
Phase 2: Proportion of Participants with normal ALT
Time frame: 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 .
Time frame: 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
Time frame: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up
Plan to share: No
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