A Single-Ascending and Repeated Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Who Have the PNPLA3 I148M Genotype
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 32
- 主要终点
- Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Adverse Event(s) (AEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3849891 in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) who have the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M genotype. Blood tests and magnetic resonance imaging of the liver will be performed to determine the effects of LY3849891 on MASLD and assessment of resolution of liver fibroinflammation. Blood tests will also determine how long it takes the body to eliminate LY3849891. This is a 2-part study and may last up to 32 weeks for each participant and may include 12 visits in parts A and B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a body mass index (BMI) within the range greater than or equal to (≥) 25 and less than (<) 50 kilogram per square meter (kg/m²) inclusive
- •Participants must have liver fat content ≥10% in Part A and ≥8% for Part B as determined by MRI-PDFF
- •Participants must be carriers of the PNPLA3 I148M allele
- •Participants with or without type 2 diabetes mellitus (T2DM)
- •o For participants with T2DM, hemoglobin A1c (HbA1c) <8% in Part A and <9% in Part B
- •Male participants agree to use an effective method of contraception for the duration of the study and for 90 days after the last dose of study intervention
- •Women not of childbearing potential may participate and include those who are: infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or those who are postmenopausal
排除标准
- •Participants must not have known or suspected alcohol abuse (>14 units/week for women and >21 units/week for men) or active substance abuse
- •Participants must not have evidence of cirrhosis or other forms of liver disease
- •Participants must not have heart attack, stroke, or hospitalization for congestive heart failure in the past 3 months
- •Participants must not have active cancer within the last 5 years
- •Participants must not have uncontrolled high blood pressure
- •Participants must not have renal impairment with estimated glomerular filtration rate (eGFR) <60 milliliter per minute per 1.73 square meter (ml/min/1.73m²)
- •Participants must not have a diagnosis of type 1 diabetes
- •Participants must not have a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve) or other contraindications for MRI
研究组 & 干预措施
Placebo (Part A)
Placebo administered SC
干预措施: Placebo (Drug)
Placebo (Part B)
Placebo administered SC
干预措施: Placebo (Drug)
LY3849891 (Part A)
Single ascending doses of LY3849891 administered subcutaneously (SC)
干预措施: LY3849891 (Drug)
LY3849891 (Part B)
Repeated doses of LY3849891 administered SC
干预措施: LY3849891 (Drug)
结局指标
主要结局
Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Adverse Event(s) (AEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Predose up to 26 weeks post dose
A summary of TEAEs and AEs, regardless of causality, will be reported in the Reported Adverse Events module
Part B: Pharmacodynamics (PD): Mean change from baseline on liver inflammation and fibrosis measured by magnetic resonance imaging (MRI)
时间窗: Baseline through 24 weeks
PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI
次要结局
- Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)(Predose through Week 26)
- Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891(Predose through Week 26)
- Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891(Predose through Week 26)
- Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891(Predose through Week 26)
- Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF(Predose through Week 24)
- Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite(Predose through Week 24)
- Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite(Predose through Week 24)
- Part B: PK: Tmax of LY3849891 and its metabolite(Predose through Week 24)