2023-508248-23-00招募中3 期
A randomised, double-blind, placebo-controlled, multicentre, Phase 3 study evaluating efficacy and safety of lanifibranor followed by an active treatment extension in adult patient with non-cirrhotic non-alcoholic steatohepatitis (NASH) and fibrosis 2 (F2)/fibrosis 3 (F3) stage of liver fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Inventiva
- 入组人数
- 236
- 试验地点
- 94
- 主要终点
- 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.
研究概览
简要总结
The primary objectives of both periods in the main cohort are: • Double-blind placebo-controlled (DBPC) period (Part A) To assess the effect of lanifibranor compared to placebo on NASH resolution and improvement of fibrosis assessed by liver histology. • Double-blind active treatment extension (ATE) period (Part B) To assess the safety of lanifibranor beyond the DBPC period.
研究设计
- 分配方式
- Randomized
- 主要目的
- Active treatment extension (ATE) period
- 盲法
- Double (Carer, Monitor, Investigator, Analyst, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Able to understand the nature of the study, willing and able to comply with the study procedures and restrictions, and able to provide signed, dated and written informed consent obtained before any study-related activities, sampling or analysis.
- •The patient will be willing to continue on the study in case of moving or relocation during the first 72 weeks of the study.
- •Male or female, aged ≥18 years at the time of signing informed consent 4.If biopsy is performed before Screening, i.e. if a historical biopsy is available, a histological diagnosis of NASH with liver fibrosis must be made no more than 7 months before randomisation
- •Main cohort: Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF): a.Steatosis score ≥1 b.Activity score: A3 or A4 c.Fibrosis score: F2 or F3 Exploratory cohort: Patients who, upon central biopsy reading process, do not meet the eligibility criteria described above but fulfil the following criteria: diagnosis of NASH according to the Steatosis-Activity- Fibrosis (SAF): a) Steatosis score ≥1 b) Activity score ≥2 with SAF-Inflammation score ≥1 and SAF-Ballooning score ≥1 c) Fibrosis score: F1 to F3
- •Model for End-Stage Liver Disease (MELD) score ≤12 (unless patient is on anticoagulants)
- •For patients receiving the concomitant medications listed below: no qualitative change in dose are allowed (changes having minimal clinical impact like temporary cessation/change between class of drugs are allowed), for the specified period prior to the qualifying liver biopsy and dose must remain stable from the time of the liver biopsy until the Baseline visit (Visit 0): a. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists including combinations) or sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months b. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months c. Statins for at least 3 months d. Anti-obesity treatments for at least 6 months
- •For patients receiving concomitant medications not covered by criterion #7 and that may impact safety or efficacy evaluation (antidiabetic treatments other than GLP1 (or combinations) receptor agonists and SGLT2 inhibitors, antihypertensives, antidepressants, cardiovascular, antihyperlipidemic) no qualitative change in dose are allowed for at least 3 months prior to the Baseline visit (Visit 0) or for at least 8 weeks prior to Screening visit for herbal/dietary supplement with potential liver toxicity or those with unknown composition and dose must remain stable until the Baseline visit (Visit 0)
- •For overweight/obese patient, history of at least 1 unsuccessful attempt to reduce body weight by diet and/or exercise within the past 6 years
- •Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
- •Patient agrees to follow recommendations with lifestyle modifications, which will be monitored throughout the whole study period.
- •Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory.
排除标准
- •Liver-related: 1.Documented causes of chronic liver disease other than NASH including, but not restricted to: a.Viral hepatitis b.Drug-induced liver disease c.Alcoholic liver disease d.Autoimmune hepatitis (See Exclusion criteria 44 for more information) e.Wilson's disease f.Haemochromatosis g.Primary biliary cholangitis h.Primary sclerosing cholangitis i.Alpha-1-antitrypsin deficiency j.Chronic portal vein thrombosis or splenic vein thrombosis 2.Histologically documented liver cirrhosis in the most recent historical biopsy (fibrosis stage F4) or suspicion at screening of cirrhosis based on clinic biochemical and imaging criteria 3.History or current diagnosis of hepatocellular carcinoma (HCC) 4.History of or planned liver transplant 5.Inability or unwillingness to undergo a liver biopsy at Screening (if a suitable historical biopsy is unavailable for central review) and at Week 72 6.Positive human immunodeficiency virus (HIV) serology 7.ALT or AST >5 × ULN 8.Abnormal synthetic liver function of any of the following: a.Albumin below the lower limit of the normal range b.International normalised ratio (INR) ≥1.3 (unless patient is on anticoagulants) c.Total bilirubin level ≥1.5 mg/dL (25.6 μmol/L) Patients with a history of Gilbert's syndrome can be enrolled if the direct bilirubin is ≤0.45 mg/dL (7.7 μmol/L) 9.Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males 10.Leucocytes count < LLN. A lower count is acceptable in patients with benign ethnic neutropenia, if considered to be clinical insignificant by the investigator. 11.Platelet count <140,000/μL. 12.Alkaline phosphatase (ALP) >2 × ULN 13.Patient currently receiving any approved treatment for NASH 14.Current or recent history (<5 years) of significant alcohol consumption, which is typically defined as higher than 30 g pure alcohol per day for men and as higher than 20 g pure alcohol per day for women 15.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: 16.HbA1c >9% at Screening 17.Diabetes mellitus other than type 2 18.-
- •Refer to protocol for full list Autoimmune related: 44.Any patient with a predisposition to autoimmune liver disease, incl: a)Signs on liver biopsy suggestive of autoimmune liver disease b)Family history of autoimmune liver disease in a first degree relative c)Autoimmune thyroid disease 1.Diagnosis of autoimmune thyroid disease 2.Thyroid replacement hormone unless documented for reason of primary thyroid insufficiency 3.Positive autoimmune antibodies associated with abnormal thyroid function testing (TSH, T4 or free T3) i.Anti-thyroid peroxidase antibody (TPO) or ii.Anti-TSH receptor antibodies (TRAb) d)History of or positive testing at screening for: 1.Anti-nuclear antibodies (ANA) at a dilution of 1:320 or greater 2.Anti-mitochondrial antibodies (AMA) 3.Anti-smooth muscle antibodies (ASMA) at a dilution of 1:320 or greater 4.Anti-liver kidney microsomal type 1 antibodies (LKM1) 5.Anti-liver cytosol type 1 antibody (LC1)
结局指标
主要结局
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.
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
- Resolution of NASH and no worsening of fibrosis at Week 72, defined by NASH CRN scores for ballooning of 0, inflammation of 0 to 1, and no increase in fibrosis score when compared to Baseline; Improvement of fibrosis and no worsening of NASH at Week 72, defined by a decrease in NASH CRN fibrosis score ≥1 stage from Baseline and no increase in scores for ballooning, inflammation, or steatosis
研究者
Martine Baudin
Scientific
Inventiva
研究点 (94)
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