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

Phase 2RecruitingNCT07096193

Gilead Sciences107 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

107

Conditions

Chronic Hepatitis Delta

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 ) \> 100 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.

Locations (6)

Investigative Site

Anaheim, California, United States

RECRUITING

IMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba"

Chinsinau, Moldova

RECRUITING

PMSI Clinical Republican Hospital "Timofei Mosneaga"

Chisinau, Moldova

RECRUITING

Korea University Ansan Hospital

Ansan-si, South Korea

RECRUITING

The Catholic University of Korea Bucheon St. Mary's Hospital

Bucheon-si, South Korea

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

RECRUITING

Outcomes

Primary Outcomes

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; AUClast of GS-4321

AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.

Time frame: First dose up to 24 Weeks

Phase 1: Serum PK Parameter: AUCinf

AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time.

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

Secondary Outcomes

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 AUCtau 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 at Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96

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 at Weeks 24, 48, and 96

Time frame: Weeks 24, 48, 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

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

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts