NCT05583344进行中（未招募）2 期
17 β-Hydroxysteroid Dehydrogenase Type 13 Minimization for the Treatment of NASH (HORIZON): A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of GSK4532990 in Adults With Nonalcoholic Steatohepatitis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 284
- 试验地点
- 171
- 主要终点
- Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort
研究概览
简要总结
The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and advanced fibrosis on biopsy (F3 or F4). The study duration will be up to 76 weeks including the screening period. The treatment duration will be up to 52 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body Mass Index (BMI) ≥25 kilogram per meter square (kg/m^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening.
- •In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension.
- •A liver biopsy at baseline showing NAFLD Activity Score (NAS) >=4 with at least 1 point each in steatosis, inflammation and ballooning and either Fibrosis 3 or Fibrosis 4 using NASH CRN Scoring System.
- •Able and willing to comply with all study assessments, including a liver biopsy at Week 52.
排除标准
- •Current alcohol consumption ≥14 standard drinks (24 units, 196 g ethanol) per week for females or ≥21 standard drinks (37 units, 294g ethanol) per week for males.
- •Weight reduction surgery or procedures (including gastric banding and intragastric balloon insertion) within 2 years of Screening 1 and/or planned during the study.
- •History of cancer within previous 2 years from Screening 1, except basal or squamous cell carcinoma of the skin or in situ cervical carcinoma or any other type of cancer which has been treated medically or surgically with curative outcome.
研究组 & 干预措施
Low Dose GSK4532990
Experimental
干预措施: GSK4532990 (Drug)
High Dose GSK4532990
Experimental
干预措施: GSK4532990 (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort
时间窗: At Week 52
Improvement in histological fibrosis is assessed with Clinical research network (CRN) Scoring. No worsening of NASH is defined as no increase in the NAFLD Activity Score (NAS) for steatosis, ballooning, or inflammation.
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - F3 Cohort
时间窗: At Week 52
NASH resolution is defined as a ballooning score of 0 and an inflammation score of 0-1. No worsening of fibrosis is defined as no increase in CRN fibrosis score.
次要结局
- Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort(Baseline (Day 1) and up to Week 52)
- Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants)(At Week 52)
- Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants)(At Week 52)
- Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - F3 Cohort(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - F3 Cohort(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort(Baseline (Day 1) and at Week 24 and 52)
- Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort(At Week 52)
- Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - F3 Cohort(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in Pro-peptide of type III collagen (Pro-C3) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in Enhanced Liver Fibrosis (ELF) Score - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and at Week 24 and 52)
- Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort(At Week 24)
- Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and at Week 24 and 52)
- Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and at Week 24 and 52)
- Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - Pooled Cohort (F3 participants and F4 participants)(At Week 52)
- Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24 - Pooled Cohort (F3 participants and F4 participants)(At Week 24)
- Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and at Week 24 and 52)
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort(Up to Week 66)
- Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort(Baseline (Day 1) and up to Week 52)
- Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F3 Cohort(Baseline (Day 1) and up to Week 52)
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort(Up to Week 66)
- Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and up to Week 52)
- Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F4 Cohort(Baseline (Day 1) and up to Week 52)
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants)(Up to Week 66)
- Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and up to Week 52)
- Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and up to Week 52)
- Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - Pooled Cohort (F3 participants and F4 participants)(Baseline (Day 1) and up to Week 52)
- Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F3 Cohort(Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Maximum observed concentration (Cmax) of GSK4532990- F3 Cohort(Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort(Up to Week 52)
- Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F4 Cohort(Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Maximum observed concentration (Cmax) of GSK4532990- F4 Cohort(Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort(Up to Week 52)
研究者
研究点 (171)
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