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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 31
- 主要终点
- Phase 2: Proportion of Participants with Combined Response
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •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.
排除标准
- •Positive serum or urine pregnancy test.
- •Participants with plans to breastfeed during the study period.
- •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 ≥
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1: GS-4321
Participants will receive single escalating doses of GS-4321.
干预措施: GS-4321 (Drug)
Phase 1: Placebo
Participants will receive placebo to match the single escalating doses of GS-4321
干预措施: GS-4321 Placebo (Drug)
Phase 2: GS-4321
Participants will receive multiple escalating doses of GS-4321 up to 96 weeks.
干预措施: GS-4321 (Drug)
结局指标
主要结局
Phase 2: Proportion of Participants with Combined Response
时间窗: 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).
Phase 1: Serum PK Parameter: Cmax
时间窗: First dose up to 24 Weeks
Cmax is defined as the maximum observed concentration of drug.
Phase 1: Serum PK Parameter: Tmax
时间窗: First dose up to 24 Weeks
Tmax is defined as the time (observed time point) of Cmax.
Phase 1: Serum PK Parameter: t1/2
时间窗: First dose up to 24 Weeks
Phase 1: Serum Pharmacokinetic (PK) parameter; AUC of GS-4321
时间窗: First dose up to 24 Weeks
AUC is defined as the area under the concentration versus time curve
Phase 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: First dose up to 24 Weeks
Cmax is defined as the maximum observed concentration of drug.
Phase 1: Serum PK Parameter: Tmax
时间窗: First dose up to 24 Weeks
Tmax is defined as the time (observed time point) of Cmax.
Phase 1: Serum PK Parameter: t1/2
时间窗: First dose up to 24 Weeks
Phase 2: Proportion of Participants with Combined Response
时间窗: 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).
次要结局
- 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)
- 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(Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, and 96)
- Phase 2: Serum PK Parameters AUC of GS-4321(Up to 96 weeks)
- 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: Change From Baseline in Liver Stiffness by Elastography(Weeks 24, 48, and 96)
- 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)
- 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 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 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)
- 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 at Weeks 24, 48, and 96(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)
- 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)