Chronic Hepatitis Delta
Conditions
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 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
DRUGGS-4321
Administered subcutaneous (SC) or intravenously IV
DRUGGS-4321 Placebo
Administered SC
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events | 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 | 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 | 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 | First dose up to 24 Weeks | AUC is defined as the area under the concentration versus time curve |
| 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 normal alanine aminotransferase (ALT) normalization (ALT \< upper limit of normal (ULN) at week 24). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 normal ALT (ALT < ULN). | Weeks 4, 8, 12, 16, 20, 36, 48, 60, 72, 84, and 96 | — |
| Phase 2: Change From Baseline in HDV RNA | Baseline, Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96 | — |
| 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 plus 48 weeks of posttreatment follow-up | — |
| Phase 2: Proportion of Participants With Undetectable HDV RNA | 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 | Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84 and 96 | — |
| Phase 2: Change From Baseline in Liver Stiffness by Elastography | Weeks 24, 48, and 96 | — |
| Phase 2: Proportion of Participants with normal ALT | 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 | 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 . |
| 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 AUC of GS-4321 | Up to 96 weeks | — |
| Phase 2: Serum PK Parameters Cmax of GS-4321 | Up to 96 Weeks | — |
Countries
Bulgaria, Germany, Italy, Moldova, Romania, South Korea, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed