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
200
Administered subcutaneous (SC) or intravenously IV
Administered SC
Administered SC
Investigative Site
Anaheim, California, United States
RECRUITINGUniversity of California, San Diego - Altman Clinical and Translational Research Institute
La Jolla, California, United States
RECRUITINGUniversity of Louisville, Clinical Trials Unit
Louisville, Kentucky, United States
RECRUITINGUniversity of Maryland, Institute of Human Virology, Clinical Research Unit
Baltimore, Maryland, United States
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
AUC is defined as the area under the concentration versus time curve
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
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 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
Gilead Clinical Study Information Center
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The New York-Presbyterian Hospital
New York, New York, United States
RECRUITINGUniversity Multi-profile Hospital for Active Treatment "SofiaMed" 00D
Sofia, Bulgaria
RECRUITINGMedizinische Hochschule Hannover, Address: Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
Hanover, Germany
RECRUITINGFondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, SC Gastroenterologia ed Epatologia
Milan, Italy
RECRUITINGIMSP Spitalul Clinic de Boli Infectioase "Toma Ciorba"
Chinsinau, Moldova
RECRUITINGPMSI Clinical Republican Hospital "Timofei Mosneaga"
Chisinau, Moldova
RECRUITING...and 18 more locations
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
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