A Phase II, Randomized (1:1) Open Label Study to Assess the Efficacy and Safety of Eltrombopag in Combination With Dexamethasone Compared to Dexamethasone, as First-line Treatment in Adult Patients With Newly Diagnosed Immune Thrombocytopenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Percentage of Patients With Sustained Response Off Treatment at 52 Weeks
研究概览
简要总结
The purpose of this study was to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce sustained response off treatment in patients with newly-diagnosed ITP versus 1-3 cycles of dexamethasone monotherapy.
The unmet clinical need and the potential for eltrombopag when added to steroids to improve the treatment outcome and the potential to induce sustained response off treatment serve as the basis for clinical investigation of eltrombopag in first-line ITP.
详细描述
This is a Phase II, multicenter, 1:1 randomized, open-label study that compared the efficacy and safety of eltrombopag in combination with a short course of high-dose dexamethasone to 1-3 cycles of high-dose dexamethasone monotherapy, as first-line treatment in adult patients with newly diagnosed ITP.
Adult patients with newly diagnosed ITP who had platelet counts < 30 × 10^9/L and required treatment were screened, and if eligible, were randomized to either Arm A (eltrombopag in combination with a short course of dexamethasone) or Arm B (1-3 cycles of dexamethasone monotherapy).
The study was conducted in the following periods:
Screening Period: Patients were screened for 14 days based on the inclusion and exclusion criteria.
Treatment Period: Arm A: Patients were treated for 26 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10^9/L and maintained counts ≥ 30 × 10^9/L during the tapering phase were eligible for treatment discontinuation. Duration of tapering before treatment discontinuation at Week 26 was 6 weeks. Arm B: Patients were treated up to 12 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10^9/L and maintained counts ≥ 30 × 10^9/L after 1-3 cycles of dexamethasone treatment were eligible for treatment discontinuation. Patients with platelet counts < 30 × 10^9/L after 3 cycles of dexamethasone treatment were offered a course of eltrombopag treatment within the study and were discontinued from study at week 52.
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
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Men and women ≥ 18 years of age
- •Newly diagnosed with primary ITP (time from diagnosis within 3 months)
- •Platelet count < 30 × 109/L at screening and a need for treatment (per physician's discretion) Note: If pre-treatment is necessary, platelet count data performed directly before pre-treatment (can be used for study inclusion (screening value). Treatment-naïve patients will be included based on their platelet counts performed at screening
排除标准
- •Previous history of treatment for ITP, except any ITP-directed therapy for a maximum of 3 days within 7 days before randomization
- •Patients with diagnosis of secondary thrombocytopenia
- •Patients who have life threatening bleeding complications per physician´s discretion
- •Patients with a history of thromboembolic events in the 6 months preceding enrollment or known risk factors for thromboembolism
- •Serum creatinine > 1.5 mg/dL
- •Total bilirubin (TBIL) > 1.5 × upper limit of normal (ULN)
- •Aspartate transaminase (AST) > 3.0 × ULN
- •Alanine transaminase (ALT) > 3.0 × ULN
- •Patients who are human immune deficiency virus (HIV),hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive
- •Patients with hepatic impairment (Child-Pugh score > 5)
- •Patients with known active or uncontrolled infections not responding to appropriate therapy
- •History of current diagnosis of cardiac disease or impaired cardiac function denoted
- •Patients who have active malignancy
- •Patients with evidence of current alcohol/drug abuse
- •Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures
- •Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1
- •Women of child-bearing potential and males unwilling to use adequate contraception during the study
研究组 & 干预措施
Eltrombopag + Dexamethasone
Patients were treated with eltrombopag in combination with a standard high-dose dexamethasone (1 cycle: 40 mg once daily (QD) from day 1-4) to induce sustained response off treatment.
干预措施: Eltrombopag (Drug)
Eltrombopag + Dexamethasone
Patients were treated with eltrombopag in combination with a standard high-dose dexamethasone (1 cycle: 40 mg once daily (QD) from day 1-4) to induce sustained response off treatment.
干预措施: Dexamethasone (Drug)
Dexamethasone
Patients were treated with a standard high-dose dexamethasone (1-3 cycles: 40 mg QD day 1-4 at 4 weeks intervals (or at 14-28 days intervals if needed) to induce sustained response off treatment.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Percentage of Patients With Sustained Response Off Treatment at 52 Weeks
时间窗: Study treatment discontinuation until week 52
Sustained response off treatment at 52 weeks is defined as maintenance of platelet count ≥ 30 × 10\^9/L after treatment discontinuation until Week 52 in the absence of bleeding events ≥ Grade II or use of any rescue medication at all visits until Week 52. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding.
次要结局
- Percentage of Patients With Overall Response at Week 52(Study treatment discontinuation until week 52)
- Duration of Sustained Response Off Treatment(from last dose of study treatment until loss of response, approx. 52 weeks)
- Overall Response by Week 4(By Week 4)
- Complete Response by Week 4(By Week 4)
- Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points(Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53)
- Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points(Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53)
- Time to Overall Response (TOR)(Time from starting study treatment to achievement of complete response (up to 52 weeks))
- Time to Complete Response(Time from starting study treatment to achievement of complete response (up to 52 weeks))
- Duration of Overall Response (OR) and Complete Response (CR)(Achievement of overall or complete response until loss of response (up to 52 weeks))
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire(Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM))(Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53)
- Incidence and Severity of Bleeding Events(Baseline up to 52 weeks)