A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With a Single Arm Open-label Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 231
- 试验地点
- 94
- 主要终点
- Part A, Part B, Part C, and Part D: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
研究概览
简要总结
This is a randomized, blinded, placebo-controlled study of Efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (NASH), with a single arm open-label extension. It includes Parts A, B, C and D.
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
- Double (Participant, Investigator)
盲法说明
Part C - Open Label; Part D - Open Label
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
- •(Part A and Part B):
- •Participant is either male or female and 18 to 75 years of age inclusive, at the time of signing the informed consent
- •Obese participants with body mass index (BMI) of ≥ 27 kg/m^2
- •Hepatic fat fraction (HFF) measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) ≥8%
- •Liver fibrosis assessment based on a vibration controlled transient elastography (VCTE) liver stiffness measurement (LSM) score of 7.0 to 9.9 kPa (Part A only) inclusive or 7.0 to 20.0 kPa (Part B only) inclusive and Liver injury assessment measured by aspartate aminotransferase (AST) >25U/L. A qualifying historical biopsy (confirmed eligibility based on the central pathology read) supersedes the LSM, controlled attenuation parameter (CAP) score criteria and AST criteria.
- •Histopathologically confirmed F2 or F3 stage NASH on a diagnostic liver biopsy performed during Screening or within 6 months prior to the first day of dosing for historical biopsies (Part B only).
- •History or presence of at least 2 of 4 components of metabolic syndrome: obesity/overweight, dyslipidemia (high triglycerides and/or low high density lipoprotein [HDL]), type 2 diabetes with elevated glycated hemoglobin (HbA1c), and hypertension.
- •Inclusion Criteria (Part C):
- •Participant must have completed the Part B of the study.
- •Participant willing to undergo liver biopsy at Week 56
- •NASH F stage <F4 at 24 week assessment in Part B
- •Inclusion Criteria (Part D):
- •BMI of ≥ 25 kg/m^2
- •Liver fibrosis based on assessments taken during screening visit
- •Participant should be willing and able to undergo liver biopsy during Screening (if a historical biopsy within 12 months prior to Screening is not available) and per protocol as judged by the Investigator.
- •Other inclusion criteria may apply
排除标准
- •(Part A and Part B):
- •Documented clinical, laboratory or radiologic evidence of cirrhosis (compensated or decompensated)
- •Triglycerides ≥ 500 mg/dL
- •Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months from Screening, whichever is smaller)
- •History of type 1 diabetes, diabetic ketoacidosis, or positive glutamic acid decarboxylase (GAD) auto-antibodies (latent autoimmune diabetes in adults)
- •Hemoglobin A1c > 9.5%
- •Participants with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).
- •Exclusion Criteria (Part C):
- •Participants that received their 24 week dose in Part B > 10 weeks prior to enrollment into Part C
- •Exclusion Criteria (Part D):
- •Other causes of chronic liver disease
- •Documented evidence or history of decompensated liver cirrhosis.
- •History of type 1 diabetes or poorly controlled type 2 diabetes.
- •History of malignancy.
- •Use of other investigational drugs.
- •Other exclusion criteria may apply
研究组 & 干预措施
Part D: Efimosfermin Dose 1 or PBO
干预措施: Efimosfermin (Drug)
Part D: Efimosfermin Dose 1 or PBO
干预措施: Placebo (Drug)
Cohort A1: Efimosfermin Dose 1 or placebo (PBO)
干预措施: Efimosfermin (Drug)
Cohort A1: Efimosfermin Dose 1 or placebo (PBO)
干预措施: Placebo (Drug)
Cohort A2: Efimosfermin Dose 2 or PBO
干预措施: Efimosfermin (Drug)
Cohort A2: Efimosfermin Dose 2 or PBO
干预措施: Placebo (Drug)
Cohort A3: Efimosfermin Dose 3 or PBO
干预措施: Efimosfermin (Drug)
Cohort A3: Efimosfermin Dose 3 or PBO
干预措施: Placebo (Drug)
Cohort A4: Efimosfermin Dose 4 or PBO
干预措施: Efimosfermin (Drug)
Cohort A4: Efimosfermin Dose 4 or PBO
干预措施: Placebo (Drug)
Cohort A5: Efimosfermin Dose 5 or PBO
干预措施: Efimosfermin (Drug)
Cohort A5: Efimosfermin Dose 5 or PBO
干预措施: Placebo (Drug)
Part B: Efimosfermin Dose 1 or PBO
干预措施: Efimosfermin (Drug)
Part B: Efimosfermin Dose 1 or PBO
干预措施: Placebo (Drug)
Part C: Efimosfermin Dose 1
干预措施: Efimosfermin (Drug)
Part D: Efimosfermin Dose 6 or PBO
干预措施: Efimosfermin (Drug)
Part D: Efimosfermin Dose 6 or PBO
干预措施: Placebo (Drug)
结局指标
主要结局
Part A, Part B, Part C, and Part D: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
时间窗: Until End of study/Early Termination (Day 393)
The effects of Efimosfermin on safety and tolerability will be assessed.
Part A, Part B, Part C, and Part D: Changes from Baseline in systolic and diastolic blood pressure (BP)
时间窗: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
The effects of Efimosfermin on safety and tolerability will be assessed.
Part A, Part B, Part C, and Part D: Changes from Baseline in heart rate
时间窗: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
The effects of Efimosfermin on safety and tolerability will be assessed.
Part A, Part B, Part C, and Part D: Number of participants with Grade 3 and Grade 4 laboratory abnormalities
时间窗: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
The effects of Efimosfermin on safety and tolerability will be assessed.
次要结局
- Part A only: Efimosfermin serum concentration on Day 8 of the first dose(Day 8)
- Part A only: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)(Pre-dose at Days 15, 29, 43, 57, 71, 85 and 113 (End of study/Early termination) for bi-weekly schedule; pre-dose on Days 29, 57, 85 and 113 (End of study/Early termination) for the monthly schedule)
- Part B only: Efimosfermin serum concentration on Day 7(Day 7)
- Part B and Part C: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)(Pre-dose at Days 29, 57, 85, 113, 141, 169, 225, 253, 281, 309, 316, 323, 330, 337, 365 and at Day 393 (End of study/Early Termination))
- Part B and Part C: Area under the serum concentration-time curve (AUC) for Efimosfermin for one dosing interval at steady state(At Days 121, 127, 134, 316, 323, 330 and pre-dose at Days 141 and 337)