NCT04309773招募中3 期
Double Blind, Multicentric, Randomized, Placebo-controlled Trial, Evaluating the Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC).
研究概览
简要总结
The objectives of this study are to evaluate the effect of bezafibrate treatment compared to placebo on efficacy and safety in patients with primary sclerosing cholangitis (PSC) and persistent cholestasis despite ursodeoxycholic acid therapy
详细描述
This is a Phase 3, randomized, double-blind, placebo-controlled, evaluation of the efficacy and safety of Bezafibrate in subjects with PSC and persistent cholestasis despite ursodeoxycholic acid therapy (UADC).
Design:
- A multicentre, double-blind placebo controlled, randomised clinical trial
- 35 centers participants to the recruitment (French Network of Reference and Competence Centers for Rare Diseases: "inflammatory biliary diseases and autoimmune hepatitis" (MIVBH), including Saint-Antoine hospital, Paris as reference coordinator center)
Sample size :
104 patients, 52 in each group
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
- Triple (Participant, Care Provider, Investigator)
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
- •Males or females ≥ 18 and ≤ 75 years
- •Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC
- •Colonoscopy (already done or scheduled before randomization) within the last 5 years (or within 6 months if IBD is associated to PSC) with neither cancer nor allgrade dysplasia or endoscopy of the ileal reservoir (already done or scheduled before randomization) within the last 2 years in patients with ileo-anal anastomosis
- •ALP ≥ 1.5 ULN at baseline
- •Treatment with stable dose of UDCA (15-20 mg/kg/d) for ≥ 6 months before inclusion (rounded to the nearest unit, e.g 14.5 mg/kg/d would be 15mg/kg/d).
- •Using contraceptive in childbearing women
- •Affiliation to a social security system (AME excepted)
- •Signed informed consent
排除标准
- •Child-Pugh score B or C
- •Ascites or digestive hemorrhage (or history of)
- •Total bilirubin in the last 3 months > 50 μmole/L (3 mg/dl)
- •Gilbert syndrome defined as unconjugated bilirubinemia > 12 μmol/L
- •Albumin in the last 3 months < ULN (according to the laboratory reference value)
- •Prothrombin index in the last 3 months < 70%
- •Platelets count in the last 3 months < 100000/mm3
- •ALT or AST > 5 ULN in the last 3 months
- •Prior liver transplantation
- •Treatment with a fibrate within the last 3 months inclusion or with a statin at inclusion
- •Current active IBD defined as either current use of systemic corticosteroid therapy > 10 mg/day or budesonide > 3 mg /day or immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate mofetil, mTor inhibitors, JAK inhibitors) or a partial Mayo score > 2 in patients with ulcerative colitis (UC) or a Crohn's Disease Activity Index (CDAI) > 150 in patients with Crohn's disease (CD)
- •Dose change of treatment for associated IBD ≤3 months prior to inclusion
- •Current or history of colonic cancer or all-grade dysplasia described at the last colonoscopy (Patients with a history of colon cancer and treated by total colectomy without recurrence for at least 5 years are eligible)
- •Any other cause of liver damage ((positive test for HBV, HCV, or HIV, excessive alcohol consumption, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease, autoimmune hepatitis defined by the presence of at least 2 of the 3 following criteria; 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN, 3) interface hepatitis on liver biopsy)
- •Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 > 4 ULN)
- •History of acute cholangitis in the last 3 months prior to inclusion or current acute cholangitis
- •Endoscopic treatment for bile duct stenosis ≤ 3 months prior to inclusion or planned within 3 months post randomization date
- •History of or established or suspected hepatobiliary carcinoma.
- •Any severe comorbidity that may reduce life expectancy
- •History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening)
- •Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates
- •Known photosensitivity or photoallergy reactions to fibrate
- •Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in 400 mg SR tablets of bezafibrate and in placebo tablets
- •Pregnancy (or desire for)
- •Renal insufficiency (clearance < 60 ml/min or serum creatinine level > 130 μmole/L)
- •Breastfeeding
- •Participation in any other interventional study or in the exclusion period any other interventional study
- •Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
- •Results of colonoscopy not available or > 5 years (or > 6 months if IBD is associated to PSC) or with cancer or all-grade dysplasia or results of endoscopy of the ileal reservoir not available or > 2 years in patients with ileo-anal anastomosis
- •Randomization exclusion criteria:
- •Positive test for HBV (positive HBs Ag), HCV (positive HCV RNA), or HIV (positive serology)
- •Pregnancy (or desire for in the 2 next years)
- •Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 > 4 ULN)
- •Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
- •Current acute cholangitis
研究组 & 干预措施
Bezafibrate in addition to standard UDCA therapy
Experimental
Bezafibrate (400mg) in addition to standard 15-20 mg/kg/day UDCA therapy ("experimental" arm)
干预措施: Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy (Drug)
Placebo of Bezafibrate in addition to standard UDCA therapy
Placebo Comparator
Placebo of Bezafibrate in addition to standard 15-20 mg/kg/day UDCA therapy
干预措施: Placebo of Bezafibrate in addition to standard UDCA therapy (Drug)
结局指标
主要结局
To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC).
时间窗: At 24 months
Proportion of patients with serum Alkaline Phosphatase \< 1.5 ULN and a reduction of at least 15% from baseline at M24 and normal serum bilirubin and no increase of liver stiffness at M24 compared to baseline:
次要结局
- Quality of life of PSC patients(At 12 months and 24 months)
- Fatigue score(At 12 months and 24 months)
- Percentage of patients with clinical or biological adverse events(At 24 months)
- Score for pruritus(At 12 months and 24 months)
- Level of liver biochemical parameters between the two groups of patient(between month 0 and month 24)
- Occurrence of clinical events and transplant-free survival(At 24 months)
研究者
研究点 (1)
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