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NCT Number: NCT07096193

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

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.

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Key information

Conditions

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

Age range

18 year–69 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University Multi-profile Hospital for Active Treatment "SofiaMed" 00D, Sofia, Bulgaria

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

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 ) > 500 IU/mL at screening.
  • Alanine aminotransferase (ALT) level > 1 × Upper limit of normal (ULN), but < 10 × ULN at screening.

Key Exclusion Criteria:

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

GS-4321

Drug

Administered subcutaneous (SC) or intravenously IV

GS-4321 Placebo

Drug

Administered SC

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. Phase 1: Serum Pharmacokinetic (PK) parameter; AUC of GS-4321

    Time frame: First dose up to 24 Weeks

    AUC is defined as the area under the concentration versus time curve

  5. Phase 1: Serum PK Parameter: Cmax

    Time frame: First dose up to 24 Weeks

    Cmax is defined as the maximum observed concentration of drug.

  6. Phase 1: Serum PK Parameter: Tmax

    Time frame: First dose up to 24 Weeks

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

  7. Phase 1: Serum PK Parameter: t1/2

    Time frame: First dose up to 24 Weeks

  8. Phase 2: Proportion of Participants with Combined Response

    Time frame: Up to 96 Weeks

    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).

Secondary outcomes

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

    Time frame: First dose up to 24 Weeks

    ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .

  2. Phase 2: Serum PK Parameters AUC of GS-4321

    Time frame: Up to 96 weeks

  3. Phase 2: Serum PK Parameters Cmax of GS-4321

    Time frame: Up to 96 Weeks

  4. Phase 2: Serum PK Parameters Tmax of GS-4321

    Time frame: Up to 96 Weeks

  5. Phase 2: Serum PK Parameters Ctrough of GS-4321

    Time frame: Up to 96 Weeks

  6. 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

  7. 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

  8. 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

  9. 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

  10. Phase 2: Change From Baseline in Liver Stiffness by Elastography

    Time frame: Weeks 24, 48, and 96

  11. Phase 2: Proportion of Participants with normal ALT

    Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96

  12. Phase 2: Proportion of Participants who Develop ADAs After Administration of Multiple Doses of GS-4321 and ADA Titer Characterization

    Time frame: First dose up to 96 Weeks plus 48 weeks of posttreatment follow-up

    ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .

  13. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Gilead Clinical Study Information Center

CONTACT

[email protected]

1-833-445-3230 (GILEAD-0)

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2025
Primary completion
2030
Study completion
2030
First posted
Jul 31, 2025
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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