A Phase 2a Study of SCY-635 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive Subjects With Genotype 1 Hepatitis C Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Undetectable HCV RNA
研究概览
简要总结
This study will examine the effectiveness of 28 days of triple combination therapy including SCY-635 with peginterferon alfa 2a and ribavirin in reducing serum HCV RNA levels. An additional 20 weeks of treatment with the currently approved standard of care will be offered to all participants. The Week 24 visit will be the last on-study visit. After the Week 24 visit, all subjects with undetectable HCV RNA will be given the option to continue treatment with standard of care for an additional 24 weeks (out to Week 48) under the care of their Principal Investigator.
详细描述
Objectives:
The primary objective of this Phase 2a study was to assess the effect of treatment with SCY-635, used in combination with peginterferon alfa-2a (PegIFN α-2a) and ribavirin (RBV), on hepatitis C viral replication (as measured by quantitative serum HCV RNA) in treatment-naive subjects with chronic genotype 1 infection who have an IL28B genotype of C/T or T/T.
The secondary objective of the study was to evaluate the safety and pharmacokinetics (PK) of SCY-635 when given in combination with PegIFN α-2a and RBV.
Primary Endpoints:
Proportion of subjects in each cohort with an undetectable serum HCV RNA level at Week 4 of treatment
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Quantifiable serum levels of HCV-specific RNA in excess of 100,000 IU/mL
- •Chronic HCV status
- •HCV genotype 1 infection and IL28B genotype of C/T or T/T
- •Liver biopsy results within 3 years prior to screening indicating the absence of cirrhosis
- •*If no previous biopsy is available, a biopsy must be performed during the screening period to qualify for randomization
- •Body mass index (BMI) between 18 and 38 kg/m2
- •Laboratory variables within acceptable ranges:
- •ALT/AST < 3 × ULN;
- •HgB > 12g/dL for females, > 13 g/dL for males;
- •total WBC count > 3000/mm3 and ANC > 1500/mm3;
- •platelets > 100,000/mm3;
- •prothrombin time (or INR) ≤ 1.2 × ULN;
- •serum albumin ≥ 3.4 g/dL;
- •total bilirubin WNL;
- •serum creatinine WNL; if serum creatinine is > ULN, then calculated creatinine clearance must be > 100 mL/min (by Cockcroft-Gault formula) for subject to be eligible
- •Subjects of childbearing potential (i.e., not surgically sterile or postmenopausal) must agree to use 2 forms of contraception from Screening until 24 weeks after completion of treatment with RBV
- •Negative urine testing for amphetamines and cocaine at Screening.
- •If female, the subject has a negative pregnancy test at Screening and on study Day 1
排除标准
- •History of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease
- •Females who are pregnant or breastfeeding
- •Males with partners who are pregnant or are planning to become pregnant
- •HCV genotype other than genotype 1 and an IL28B genotype of C/C
- •Seropositive for HIV-1 or HIV-2 or hepatitis B virus (HBV) surface antigen (HBsAg)
- •Use of any investigational agent within 3 months prior to dosing
- •Received any prior FDA-approved or investigational drug or drug regimen for the treatment of hepatitis C
- •Evidence of cirrhosis on a previous liver biopsy
- •Evidence of decompensated liver disease
- •Recipient of an organ transplant
- •Evidence of hepatocellular carcinoma
- •Evidence of ongoing alcohol or substance abuse
- •Poorly-controlled diabetes mellitus
- •Congestive heart failure or unstable cardiopulmonary condition, renal disease, or hemoglobinopathy (sickle cell anemia or thalassemia
- •History of seizure disorder
- •History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, related hospitalizations, bipolar disorder, or psychosis requiring medication
- •Concurrent medical condition or laboratory abnormality that would constitute a contra-indication for interferon use
- •History of unstable thyroid disease that would preclude administration of interferon-based therapy
- •Medical condition that requires use of systemic corticosteroids
- •Received warfarin or other anticoagulants during the 21 days immediately prior to Screening, or is expected to require warfarin or other anticoagulants during the study.
- •One or more additional known primary or secondary causes of liver disease, other than hepatitis C
- •Any other concurrent medical condition likely to preclude compliance with the schedule of evaluations, or likely to confound the efficacy or safety observations
- •12-lead ECG showing the following:
- •Corrected QTc interval ≥ 450 msec (Bazett's correction);
- •QRS > 120 msec;
- •Clinically significant abnormalities;
- •Severe retinopathy or other significant ophthalmological disorder
- •Use of any herbal supplements within 28 days prior to dosing.
- •The use of CYP3A inducers or inhibitors for at least 2 weeks prior to initiation of treatment through Week 6
研究组 & 干预措施
SCY-635 600 mg
SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: Pegasys (Drug)
Placebo
Placebo + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: Placebo (Drug)
SCY-635 600 mg
SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: Copegus (Drug)
SCY-635 600 mg
SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: SCY-635 (Drug)
Placebo
Placebo + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: Copegus (Drug)
Placebo
Placebo + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
干预措施: Pegasys (Drug)
结局指标
主要结局
Undetectable HCV RNA
时间窗: Week 4
次要结局
- Undetectable HCV RNA(Week 24)
- Partial Early Virologic Response(Week 12)