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

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

Overview

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.

Interventions

• Drug GS-4321
  Administered subcutaneous (SC) or intravenously IV
• Drug GS-4321 Placebo
  Administered SC
• Drug GS-4321
  Administered SC

Primary outcome measures

• 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 [Time frame: First dose up to 24 Weeks]
• Phase 1: Serum PK Parameter: Cmax [Time frame: First dose up to 24 Weeks]
• Phase 1: Serum PK Parameter: Tmax [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 [Time frame: Up to 96 Weeks]

Secondary outcome measures (12)

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

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 4 centers

• Investigative Site — Anaheim
• University of Louisville, Clinical Trials Unit — Louisville
• University of Maryland, Institute of Human Virology, Clinical Research Unit — Baltimore
• The New York-Presbyterian Hospital — New York

Romania · 4 centers

• Institutul National De Boli Infectioase Prof. Dr. Matei Bals — Bucharest
• Fundatia Dr. Victor Babes — Bucharest
• Infectious Diseases Institutul National De Boli Infectioase Prof. Matei Bals — Bucharest
• Gastromedica S.R.L. — Iași

South Korea · 4 centers

• Korea University Ansan Hospital — Ansan-si
• The Catholic University of Korea Bucheon St. Mary's Hospital — Bucheon-si
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul
• Samsung Medical Center — Seoul

Taiwan · 4 centers

• Ditmanson Medical Foundation Chia-Yi Christian Hospital — Chiayi City
• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City
• National Taiwan University Hospital — Taipei

Moldova · 3 centers

• IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba" — Chinsinau
• IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba" — Chisinau
• PMSI Clinical Republican Hospital "Timofei Mosneaga" — Chisinau

Bulgaria · 1 center

• University Multi-profile Hospital for Active Treatment "SofiaMed" 00D — Sofia

Germany · 1 center

• Medizinische Hochschule Hannover — Hanover

Italy · 1 center

• Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, SC Gastroenterologia ed Epatolog — Milan

Identifiers

NCT: NCT07096193 · GS-US-567-6968 · 2025-522729-36

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗