An Open-label, Multi-centre Rollover Study to Assess the Safety and Efficacy of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2a or Peginterferon Alfa-2b Plus Ribavirin)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
研究概览
简要总结
The purpose of this study is to test the safety and tolerability of eltrombopag when used to increase and maintain platelet count. Platelet count to be maintained at a level sufficient to facilitate initiation of antiviral therapy, to minimize antiviral therapy dose reductions, and to avoid permanent discontinuation of antiviral therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Prior participation in protocol TPL103922 or TPL108390 and completed the Week 24 Follow Up Visit in TPL103922 or TPL108390
- •Male or female ≥18 years old
- •Evidence of chronic HCV infection
- •While participating in TPL103922 or TPL108390, discontinued from study drug due to thrombocytopenia
- •Appropriate candidate for antiviral therapy with pegylated interferon plus ribavirin
- •Platelet count <75,000
- •Fertile males and females must use two forms of effective contraception during treatment and for 24 weeks after treatment
- •Ability to understand and comply with the protocol requirements and instructions
- •Ability to provide written informed consent
排除标准
- •Decompensated liver disease
- •Known hypersensitivity, intolerance, or allergy to interferon, ribavirin, eltrombopag, or their ingredients
- •History of clinically significant bleeding from oesophageal or gastric varices
- •History of arterial or venous thrombosis and two or more of the following risk factors: hereditary thrombophilic disorders; hormone replacement therapy; systemic contraception (containing estrogen); smoking; diabetes; hypercholesterolemia; medication for hypertension or cancer
- •Pre-existing cardiac disease (congestive heart failure Grade III/IV) or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
- •Evidence of hepatocellular carcinoma
- •HIV or Hepatitis B infection
- •Therapy with anti-neoplastic or immunomodulatory treatment within six months prior to eltrombopag therapy
- •Malignancy diagnosed or treated within the past five years. Except for localized basal or squamous cell carcinoma treated by local excision or malignancies that were adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival.
- •Pregnant or nursing women
- •Men with a female partner who is pregnant
- •History of alcohol/drug abuse or dependence within six months of the study start unless participating in a controlled rehabilitation programme.
- •Treatment with an investigational drug or interferon within 30 days or 5 half-lives (whichever is longer) of the screening visit
- •History or platelet clumping that prevents reliable measurement of platelet counts
- •Evidence of portal vein thrombosis within three months of baseline visit
研究组 & 干预措施
Open-label eltrombopag
Open-label eltrombopag with dose titrations to support adequate platelet counts.
干预措施: Eltrombopag (Drug)
Open-label eltrombopag
Open-label eltrombopag with dose titrations to support adequate platelet counts.
干预措施: Antiviral therapy (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
时间窗: From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Number of Participants With the Indicated Worst-case Division of Acquired Immune Deficiency Syndrome (DAIDS) Grade Increases From Screening for the Indicated Clinical Chemistry Parameters During Part 1
时间窗: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1
时间窗: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
Blood samples were collected for the measurement of hematology parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2
时间窗: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Number of Participants With Any AE and Any SAE in Part 2
时间窗: From the date of initiation of antiviral therapy (Antiviral Baseline Visit [between Study Day 14 and Study Day 65]) to the completion of the follow-up period (up to Week 96/WD)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Clinical Chemistry Parameter During Part 2
时间窗: From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2
时间窗: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
Visual acuity (VA) is defined as acuteness or clearness of vision.
Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2
时间窗: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2
时间窗: From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)
Blood samples were collected for the measurement of hematology chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
次要结局
- Number of Particpants Who Initiated Antiviral Therapy(From the start of the investigational product up to 9 weeks (median of 21 days))
- Platelet Counts at the Indicated Time Points(From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks))
- Number of Participants Achieving Antiviral Treatment Milestones of Sustained Virological Response (SVR), Rapid Virological Response (RVR), Early Virological Response (EVR), and End of Treatment Response (ETR)(From the start of investigational product in Part 2 up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks))