A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis Stages F2 and F3
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,000
- 试验地点
- 811
- 主要终点
- Safety Analyses
研究概览
简要总结
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3
详细描述
Primary objectives
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives:
Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology.
Part B To assess the safety of lanifibranor beyond the DBPC period. Secondary objectives
Key secondary objectives of Part 1:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prescreening Criteria:
- •Diagnosed with NASH on prior liver biopsy
- •Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound
- •At least 3 of the components of metabolic syndrome
- •Inclusion Criteria:
- •Male or female, aged ≥18 years at the time of signing informed consent
- •Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
- •Steatosis score ≥1
- •Activity score: A3 or A4
- •Fibrosis score: F2 or F3
- •No qualitative change in dose for the drugs listed below:
- •Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
- •Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
- •Statins: for at least 3 months
- •No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening
- •Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
- •Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.
排除标准
- •Liver-related:
- •Documented causes of chronic liver disease other than NASH
- •Histologically documented liver cirrhosis (fibrosis stage F4)
- •History or current diagnosis of hepatocellular carcinoma (HCC)
- •History of or planned liver transplant
- •Positive human immunodeficiency virus (HIV) serology
- •ALT or AST >5 × ULN
- •AST<0.6 ULN if the liver biopsy has to be performed in the scope of the study
- •Abnormal synthetic liver function as defined by Screening central laboratory evaluation
- •Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males
- •Patient currently receiving any approved treatment for NASH or obesity
- •Current or recent history (<5 years) of significant alcohol consumption
- •Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy
- •Glycaemia related:
- •HbA1c >9% at Screening
- •Diabetes mellitus other than type 2
- •Current treatment with insulin
- •Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.
- •Obesity related:
- •Bariatric surgery: Restrictive procedures are allowed, if performed >6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.
- •Cardiovascular related:
- •History of heart failure with reduced left ventricular ejection fraction (LVEF)
- •Atrial fibrillation requiring anticoagulation
- •Unstable heart failure
- •Uncontrolled hypertension at Screening (values >160/100 mm Hg)
- •General safety:
- •Women currently breastfeeding
- •Previous exposure to lanifibranor
- •Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
- •Concomitant treatment with PPAR-alpha agonists (fibrates)
研究组 & 干预措施
Lanifibranor (IVA 337) (800 mg/day)
2 Lanifibranor tablets 400mg + 1 Placebo to match tablet with food --> once a day (quaque die, QD)
干预措施: Placebo (Drug)
Matching placebo
3 Placebo to match tablets with food --> once a day (quaque die, QD)
干预措施: Placebo (Drug)
Lanifibranor (IVA 337) (800 mg/day)
2 Lanifibranor tablets 400mg + 1 Placebo to match tablet with food --> once a day (quaque die, QD)
干预措施: IVA337 (Drug)
Lanifibranor (IVA 337) (1200 mg/day)
3 Lanifibranor tablets 400mg with food --> once a day (quaque die, QD)
干预措施: IVA337 (Drug)
结局指标
主要结局
Safety Analyses
时间窗: 48 weeks after completion of DBPC period
Part B: ATE: * Using the DBPC on-treatment period, comparing the 2 active arms versus placebo * Using the DBPC +ATE on treatment periods, assessing the 2 active arms. For adverse events, adjudicated liver events, and DILI and MACE events, in addition to the raw cumulative incidence proportions, the exposure-adjusted incidence rates will be provided based on the time patients are at risk.
Resolution of NASH and improvement of fibrosis
时间窗: Part A: Date of randomisation until the date of biopsy at Week 72
Part A: DBPC: Resolution of NASH and improvement of fibrosis at Week 72, defined by NASH CRN scores for ballooning of 0 and inflammation of 0 to 1, and fibrosis score ≥1 stage decrease compared to Baseline
次要结局
未报告次要终点