A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 89bio, Inc.
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
研究概览
简要总结
Part 1: This is a multi-center evaluation of pegozafermin (administered weekly or every other week) in a randomized, double-blind, placebo-controlled study administered for 12 weeks in participants with NASH and NAFLD at high risk of NASH, including a pre-defined number of participants with biopsy confirmed NASH and fibrosis stages F1-F3 to be enrolled.
Part 2: This is a multi-center, open label evaluation of pegozafermin at 27 mg administered weekly for 20 weeks in participants with biopsy-proven NASH (NAS ≥4, fibrosis stage F2 or F3).
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 1 was blinded, Part 2 was open label
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
- •Participants must be 21 to 75 years of age inclusive, at the time of signing the informed consent form (ICF).
- •Evidence of steatosis by Fibroscan and magnetic resonance imaging based proton density fat fraction (MRI-PDFF)
- •NASH or NAFLD at high risk for NASH as reflected by AT LEAST ONE of the following:
- •Diagnosis of NASH with fibrosis (stages F1, F2 or F3), without cirrhosis, by percutaneous liver biopsy within 24 months prior to screening
- •Central obesity WITH type 2 diabetes mellitus (T2DM)
- •Central obesity WITH either increased alanine transaminase (ALT) and/or Fibroscan vibration-controlled transient elastography (VCTE) score ≥7 KPa.
- •Part 2 only: Biopsy-proven NASH in a liver biopsy obtained within 24 weeks of baseline with fibrosis stage F2 or F3 and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. A small number of high risk F1 allowed.
排除标准
- •Clinically significant disorder or a history of any illness that, in the opinion of the Investigator, might confound the results of the study, or pose additional risk to the participant by participation in the study.
- •History of type 1 diabetes.
- •Weight loss of more than 5% within 3 months prior to Day -1 or more than 10% within 6 months prior to Day -1 or planning to try to lose weight during conduct of study.
- •History of a liver disorder other than NASH or clinical suspicion of a liver disorder other than NASH
- •History of cirrhosis or evidence of cirrhosis
研究组 & 干预措施
Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)
Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Pegozafermin 9 mg QW
Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Pegozafermin 18 mg QW
Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Pegozafermin 27 mg QW
Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)
Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Pegozafermin 36 mg Q2W
Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
干预措施: Pegozafermin (Drug)
Part 1: Placebo QW or Q2W
Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85.
干预措施: Placebo (Other)
Part 2: Pegozafermin 27 mg QW
Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.
干预措施: Pegozafermin (Drug)
结局指标
主要结局
Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
时间窗: Up to 113 days
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin
时间窗: Predose and up to 168 hours postdose on Day 29
Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin
时间窗: Predose and up to 168 hours postdose on Day 29
Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin
时间窗: Predose and up to 168 hours postdose on Day 29
Part 2: Number of Participants With TEAEs
时间窗: Up to 162 days
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin
时间窗: Predose and up to 168 hours postdose on Day 29
Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis
时间窗: Day 141
NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (CRN) fibrosis score. NASH 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).
次要结局
- Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92(Baseline, Day 92)
- Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)(Part 1: Baseline, Day 92; Part 2: Baseline, Day 141)
- Part 1: Percent Change From Baseline in Adiponectin at Day 92(Baseline, Day 92)
- Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin(Up to 113 days)
- Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3)(Part 1: Baseline, Day 92; Part 2: Baseline, Day 141)
- Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92(Baseline, Day 92)
- Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50(Baseline, Day 50)
- Parts 1 and 2: Percent Change From Baseline in Body Weight(Part 1: Baseline, Day 85; Part 2: Baseline, Day 141)
- Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH(Day 141)
- Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis(Day 141)