Study of GS-4321 in Healthy Participants and Participants With Chronic Hepatitis Delta Virus
- Conditions
- Chronic Hepatitis Delta
- Interventions
- Drug: GS-4321Drug: GS-4321 Placebo
- Registration Number
- NCT07096193
- Lead Sponsor
- Gilead Sciences
- Brief 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).
The primary objective of Phase 1 of this study 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
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 nucleoside/nucleotide analogue for the treatment of hepatitis B virus (HBV) infection at enrollment.
- 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
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1: GS-4321 GS-4321 Participants will receive single escalating doses of GS-4321. Phase 1: Placebo GS-4321 Placebo Participants will receive placebo to match the single escalating doses of GS-4321 Phase 2: GS-4321 GS-4321 Participants will receive multiple escalating doses of GS-4321 up to 96 weeks.
- Primary Outcome Measures
Name Time Method Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events Phase 1: First dose up to 40 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 Phase 1: First dose up to 40 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 Phase 1: First dose up to 40 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 First dose up to 24 Weeks AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
Phase 1: Serum PK Parameter: AUCinf First dose up to 24 Weeks AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time.
Phase 1: Serum PK Parameter: Cmax First dose up to 24 Weeks Cmax is defined as the maximum observed concentration of drug.
Phase 1: Serum PK Parameter: Tmax First dose up to 24 Weeks Tmax is defined as the time (observed time point) of Cmax.
Phase 1: Serum PK Parameter: t1/2 First dose up to 24 Weeks Phase 2: Proportion of Participants with Combined Response 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 alanine aminotransferase (ALT) normalization (ALT \< upper limit of normal (ULN)).
- Secondary Outcome Measures
Name Time Method Phase 1: Proportion of Participants who Develop Antidrug Antibody (ADAs) After Administration of a Single Dose of GS-4321 and ADA Titer Characterization First dose up to 24 Weeks ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .
Phase 2: Serum PK Parameters AUCtau of GS-4321 Up to 96 weeks Phase 2: Serum PK Parameters Cmax of GS-4321 Up to 96 Weeks Phase 2: Serum PK Parameters Tmax of GS-4321 Up to 96 Weeks Phase 2: Serum PK Parameters Ctrough of GS-4321 Up to 96 Weeks Phase 2: Proportion of Participants With Undetectable HDV RNA or ≥ 2 log10 Decrease in HDV RNA From Baseline and ALT Normalization (ALT < ULN). Weeks 4, 8, 12, 16, 20, 24, 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 Baseline, Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96 Phase 2: Proportion of Participants With Undetectable HDV RNA 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 Weeks 24, 48, and 96 Phase 2: Proportion of Participants with ALT Normalization Weeks 4, 8, 12, 16, 20, 24, 36, 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 First dose up to 96 Weeks ADA Titer characterization will include proportion of participants with ADA incidence, prevalence, persistence, and transience .
Phase 2: Characterize if Emergent Variants are Associated With Reduced Susceptibility to GS-4321 in Vitro and Virologic Failure in Participants With CHD First dose up to 96 Weeks
Trial Locations
- Locations (1)
Investigative Site
🇺🇸Anaheim, California, United States
Investigative Site🇺🇸Anaheim, California, United States