A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of BIO89-100 in Subjects With Biopsy-Confirmed Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 89bio, Inc.
- 入组人数
- 222
- 试验地点
- 89
- 主要终点
- Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled study that will evaluate the safety, efficacy, tolerability of BIO89-100 in patients with biopsy-confirmed fibrosis stages F2-F3 NASH.
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
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 21 to 75
- •Biopsy-confirmed NASH with fibrosis stage F2 or F3 per NASH CRN System and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation.
- •Qualifying biopsy must be either within 6 months of screening visit or obtained during screening period
排除标准
- •Have poorly controlled high blood pressure
- •Have type 1 diabetes or poorly controlled type 2 diabetes.
- •History of cirrhosis or evidence of cirrhosis by clinical, imaging, or liver biopsy evaluation
- •Are planning to try to lose weight during the conduct of the study.
- •Have a BMI <25 kg/m2
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
BIO89-100 - 15 mg once weekly (QW)
干预措施: BIO89-100 (Drug)
BIO89-100 - 30 mg QW
干预措施: BIO89-100 (Drug)
BIO89-100 - 44 mg once every 2 weeks (Q2W)
干预措施: BIO89-100 (Drug)
Placebo QW
干预措施: Placebo (Drug)
Placebo Q2W
干预措施: Placebo (Drug)
Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension)
干预措施: BIO89-100 (Drug)
Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension)
干预措施: Placebo (Drug)
结局指标
主要结局
Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
时间窗: Week 24
Nonalcoholic fatty liver disease activity score (NAS) was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Resolution of NASH was defined as the total absence of ballooning (score=0) and absent or mild inflammation (score=0 to 1). NASH clinical research system (CRN) fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). Worsening of fibrosis was defined as progression of fibrosis greater than or equal to (≥) 1 stage in NASH CRN fibrosis score.
Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
时间窗: Week 24
Worsening of NASH was defined as increase in nonalcoholic fatty liver disease activity score (NAS) for ballooning, inflammation, or steatosis. NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score. NASH CRN fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
次要结局
- Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis(Week 24)
- Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c)(Baseline, Week 24)
- Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage(Week 24)
- Main Study: Number of Participants With at Least a 2-point Improvement in NAS Score and Are Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Responders and Alanine Aminotransferase (ALT) Responders(Week 24)
- Main Study: Percent Change From Baseline in Serum Triglycerides(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Adiponectin(Baseline, Week 24)
- Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Alanine Transaminase(Baseline, Week 12 and 24)
- Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)(Baseline, Week 12 and 24)
- Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)(Baseline, Week 12 and 24)
- Main Study: Trough Serum Concentration of Pegozafermin(Predose at Week 12 and 24)
- Main and Extension Study: Percent Change From Baseline in Alanine Transaminase(Baseline, Week 48)
- Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)(Baseline, Week 48)
- Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)(Baseline, Week 48)
- Main and Extension Study: Trough Serum Concentration of Pegozafermin(Predose at Week 48)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to Week 51)