A Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel-group Phase II Study on the Efficacy and Safety of Debio 025 Combined With Peg-IFNα2a and Ribavirin in Treatment naïve Chronic Hepatitis C Genotype 1 Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 40
- 主要终点
- Percentage of participants achieving sustained viral response (SVR) 72 weeks after treatment start
研究概览
简要总结
The purpose of this study is to compare several Debio 025 (alisporivir)/peg-IFNα2a/ribavirin triple therapies with the current standard of care (SOC) in treatment naïve chronic hepatitis C genotype 1 patients.
详细描述
This is an international, multicentre, randomised, double-blind, placebo-controlled, 4-arm, parallel-group, multiple dose phase II study comparing 3 Debio 025 (alisporivir)/peg-IFNα2a/ribavirin regimens to SOC treatment in treatment naïve chronic HCV genotype 1 patients.
Patients are randomised into 1 of 4 arms receiving either Debio 025/peg-IFNα2a/ribavirin triple therapy for a fixed treatment duration of 48 weeks (Treatment A) or 24 weeks (Treatment B), Debio 025/peg-IFNα2a/ribavirin triple therapy for a response-based treatment duration of 24 or 48 weeks (Treatment C), or blinded SOC treatment for 48 weeks (Treatment D). Follow-up is 24 weeks in all treatment arms.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged ≥ 18 and ≤ 65 years.
- •Body mass index (BMI) ≥ 18 and ≤ 32 kg/m^
- •Hepatitis B surface antigen (HbsAg) negative and HIV-1 negative.
- •Serological diagnosis of chronic hepatitis C viral infection genotype 1 for > 6 months.
- •Chronic liver disease consistent with chronic hepatitis C infection on a biopsy or FibroScan® obtained within the past 24 months (36 months for patients with incomplete/transition to cirrhosis).
- •Previously untreated for hepatitis C virus (HCV) infection (approved or investigational drug).
- •Plasma HCV RNA level lower limit ≥ 100 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent; no upper limit.
- •Neutrophil count ≥ 1500/µL; hemoglobin (Hb) ≥ 12g/dL for females and ≥ 13g/dL for males; platelets ≥ 90,000/µL.
- •Patients with incomplete/transition to cirrhosis on biopsy or an elasticity score between 9.5 and 14 kPa on FibroScan must have an abdominal ultrasound (US), computed tomographic (CT) scan, or magnetic resonance imaging (MRI) scan without evidence of hepatocellular carcinoma (within 2 months prior to randomisation) and a serum alpha-foetoprotein (AFP) < 100 ng/mL.
- •Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) < 5 times the upper limit of normal.
- •Normal or compensated liver function and absence of complicated portal hypertension as documented by the following:
- •No history of bleeding oesophageal varices;
- •Absence of ascites;
- •Absence of encephalopathy;
- •Albumin ≥ 35 g/L;
- •Total bilirubin ≤ 1.8 mg/dL (≤ 30 µmol/L);
- •Prothrombin (INR ≤ 1.5).
- •Creatinine clearance > 50 mL/min.
- •Thyroid stimulating hormone (TSH) within normal range;
- •All patients should be informed about Debio 025 and ribavirin foetotoxicity:
- •Females may participate if they are surgically sterile or post-menopausal. Pre-menopausal females may participate if they use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 4 months after the last Debio 025 or ribavirin dose.
- •Male patients must be surgically sterile or use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 7 months after the last Debio 025 or ribavirin dose.
- •Signed informed consent before any study procedures.
- •Negative pregnancy test within one week of first investigational product administration for female patients of child bearing potential.
排除标准
- •Treatment with any investigational drug within 6 months prior to the first dose of investigational product.
- •HCV genotype different from genotype
- •Any previous HCV treatment (approved or investigational).
- •Histologic evidence of complete hepatic cirrhosis (including compensated cirrhosis) based on a previous liver biopsy (if available).
- •Ongoing or recent use of any other medication (including over the counter medication and herbal products) within 2 weeks before study start or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome P450 (CYP450) 3A, substrates of P-glycoprotein 1 (P-gP), or substrates/inhibitors of organic anion-transporting polypeptides (OATP), multidrug resistance-associated protein 2 (MRP2), or bile salt export pump (BSEP) and are mentioned in the list of unauthorised medications;
- •Any medical contraindications to peg-IFNα2a and/or ribavirin treatment;
- •Any other cause of relevant liver disease other than HCV including but not limited to hepatitis B virus (HBV), drug- or alcohol-related cirrhosis, autoimmune hepatitis, haemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), or primary biliary cirrhosis (PBC).
- •Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study. Patients with risk factors (hypertension or diabetes) need to have an ophthalmologic investigation (including fundoscopy).
- •History of moderate, severe, or uncontrolled psychiatric disease, especially depression, including a history of hospitalisation or prior suicidal attempt.
- •Uncontrolled arterial hypertension, ie, patients with systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg.
- •History of pancreatitis, uncontrolled diabetes mellitus, or retinopathy.
- •Anti-nuclear antibody (ANA) titre > 1:640 at screening and/or evidence of autoimmune hepatitis on liver biopsy.
- •Alcohol consumption > 20 g/day for females and > 30 g/day for males.
- •History of major organ transplantation with an existing functional graft.
- •Pregnancy or lactation.
- •Haemoglobinopathies (thalassaemia major, sickle cell anaemia or drepanocytosis).
- •Familial history of severe neonatal cholestasis or pregnancy cholestasis.
- •Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is ≥ 20% within 2 years.
研究组 & 干预措施
Debio 025 600 mg + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Debio 025 (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Peg-IFNα2a (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Ribavirin (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 weeks + peg-IFNα2a 180 µg sc once weekly for 24 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 weeks.
干预措施: Debio 025 (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 weeks + peg-IFNα2a 180 µg sc once weekly for 24 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 weeks.
干预措施: Peg-IFNα2a (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 weeks + peg-IFNα2a 180 µg sc once weekly for 24 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 weeks.
干预措施: Ribavirin (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 or 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 or 47 weeks + peg-IFNα2a 180 µg sc once weekly for 24 or 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 or 48 weeks. Participants who achieve a rapid viral response, defined as having undetectable hepatitis C virus RNA at week 4, are treated for 24 weeks; other patients are treated for 48 weeks.
干预措施: Debio 025 (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 or 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 or 47 weeks + peg-IFNα2a 180 µg sc once weekly for 24 or 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 or 48 weeks. Participants who achieve a rapid viral response, defined as having undetectable hepatitis C virus RNA at week 4, are treated for 24 weeks; other patients are treated for 48 weeks.
干预措施: Peg-IFNα2a (Drug)
Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 or 48 weeks
Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 or 47 weeks + peg-IFNα2a 180 µg sc once weekly for 24 or 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 or 48 weeks. Participants who achieve a rapid viral response, defined as having undetectable hepatitis C virus RNA at week 4, are treated for 24 weeks; other patients are treated for 48 weeks.
干预措施: Ribavirin (Drug)
Debio 025 placebo + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 placebo orally twice daily for 7 days followed by Debio 025 placebo orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Peg-IFNα2a (Drug)
Debio 025 placebo + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 placebo orally twice daily for 7 days followed by Debio 025 placebo orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Ribavirin (Drug)
Debio 025 placebo + peg-IFNα2a + ribavirin - 48 weeks
Participants receive Debio 025 placebo orally twice daily for 7 days followed by Debio 025 placebo orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.
干预措施: Debio 025 placebo (Drug)
结局指标
主要结局
Percentage of participants achieving sustained viral response (SVR) 72 weeks after treatment start
时间窗: 72 weeks after treatment start
SVR is defined as hepatitis C virus (HCV) RNA \< 10 IU/mL (undetectable).
次要结局
- Percentage of participants achieving a rapid viral response (RVR) after 4 weeks of treatment(4 weeks after treatment start)
- Percentage of participants achieving a complete early viral response (cEVR) after 12 weeks of treatment(12 weeks after treatment start)
- Percentage of participants achieving an early viral response (EVR) after 12 weeks of treatment(12 weeks after treatment start)
- Percentage of participants achieving an end-of-treatment response (ETR) at treatment end(at end of treatment (Week 28 or Week 52))
- Percentage of participants achieving a sustained viral response 12 weeks after the end of treatment (SVR 12)(12 weeks after end of treatment (Week 40 or Week 64))
- Percentage of participants with sustained viral response 24 weeks after the end of treatment (SVR 24)(24 weeks after end of treatment (Week 52 or Week 76)