A Phase II, Open-label, Prospective, Single-arm, Study to Assess Ability of Eltrombopag to Induce Sustained Remission in Subjects With ITP Who Are Refractory or Relapsed After First-line Steroids
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 3
- 主要终点
- Percentage of Participants With Sustained Response Off Treatment (SRoT) by 12 Months
研究概览
简要总结
The purpose of this trial was to assess the ability of eltrombopag to induce sustained treatment-free remission in immune thrombocytopenia purpura (ITP) subjects who relapsed or failed to respond to an initial treatment with steroids.
详细描述
Protocol Amendment 01 added a follow-up period of 12 months for patients with sustained response off treatment at month 12 to obtain further data on response duration.
The starting dose was eltrombopag 50 mg daily (25 mg daily for Asian patients and 12.5 mg daily for Japanese patients in Japan). The starting dose for this study was consistent with the dosing guidelines approved for eltrombopag use in ITP. An increase of eltrombopag dose up to 75 mg was allowed for patients who did not respond to standard-dosage treatment and to reduce the risk of bleeding. The rationale for this increased dose was to use the minimal efficacious dosage of eltrombopag in order to achieve a platelet count ≥ 100×10^9/L and maintain it around 100×10^9/L (no counts below 70×10^9/L) for 2 months in order to allow patients to start the eltrombopag tapering and withdrawal process.
Patients who reached a platelet count of >= 100 × 10^9/L and maintained counts around 100×10^9/L for 2 months with no platelet count < 70 × 10^9/L were eligible for tapering-off and treatment discontinuation, which occurred via 25 mg reduction every 2 weeks up to 25 mg on alternate days for 2 weeks until treatment discontinuation.
Patients who successfully discontinue eltrombopag and maintained platelet count >= 30 × 10^9/L in the absence of bleeding or use of rescue therapy were followed to month 12. If a relapse (defined as platelet count <30 × 10^9/L) occurred during the 12-month treatment period, they were offered a new course of eltrombopag treatment within this timeframe at the appropriate starting dose. If a patient relapsed in the post 12-month follow-up period, no further attempts for tapering and achieving sustained response off treatment were made.
The taper-off scheme followed recommendations within the current established dosing regimen for when to consider dose adjustment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 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
- •Patients ≥ 18 years old
- •Patients with a confirmed diagnosis of primary ITP, who are not responsive or in relapse after a first line of steroid therapy ± intravenous immunoglobulin (IVIG) (used as a rescue therapy)
- •Platelet count < 30×10^9/L and assessed as needing treatment (per physician's discretion
排除标准
- •ITP patients previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG
- •Patients who relapsed more than one year after the end of first-line full course of steroid therapy
- •Patients with a diagnosis of secondary thrombocytopenia
- •Patients who have life threatening bleeding complications per investigator discretion
- •Patients who had a deep vein thrombosis or arterial thrombosis in the 6 months preceding enrollment
- •Serum creatinine ≥ 1.5 mg/dL
- •Total bilirubin > 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), hepatitis B surface antigen (HBsAg) positive
- •Patients with hepatic impairment (Child-Pugh score > 5)
- •Patients who have active malignancy
- •Patients with 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 per investigator discretion
- •History or current diagnosis of cardiac disease indicating significant risk of safety for Patients participating in the study
- •Patients with known active or uncontrolled infections not responding to appropriate therapy
- •Patients with evidence of current alcohol/drug abuse
- •Women of child-bearing potential and sexually active males unwilling to use adequate contraception during the study
- •Female Patients 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
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
eltrombopag
Participants were treated with eltrombopag to induce sustained response off treatment to reach a target platelet count of >=100×10^9/L (CR), after 1st line steroids had failed.
干预措施: eltrombopag (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Response Off Treatment (SRoT) by 12 Months
时间窗: Month 12
Sustained response off treatment (SRoT) was defined as: reaching platelet count \>= 100×10\^9/L (complete response \[CR\]) and then maintaining platelet counts around 100×10\^9/L for 2 months (no counts below 70×10\^9/L), AND then tapering off the drug until treatment discontinuation while maintaining platelet count \>= 30×10\^9/L in the absence of bleeding (no bleeding AEs) or use of any rescue therapy until month 12.
次要结局
- Estimated Median Duration of Sustained Response Off Treatment (SRoT) for Participants With Sustained Response Off Treatment at Month 12 and Who Enter 12 Months Follow-up Period(From last dose of eltrombopag to relapse, assessed up to month 24)
- Percentage of Participants With Sustained Response Off Treatment Until Month 24(Month 15, 18, 21 and 24)
- Percentage of Participants With Recovery Response in Case of Loss of Response During or After Tapering of Eltrombopag Until Month 24(Up to month 24)
- Median Duration of Sustained Response Off Treatment (SRoT) After Treatment Discontinuation for Participants With Sustained Response Off Treatment(From last dose of eltrombopag to month 12)
- Estimated Median Duration of Sustained Response Off Treatment (SRot) for All Patients(From last dose of eltrombopag to month 24)
- Percentage of Participants With Early Response Within First Month(By 1 month)
- Relative Change From Baseline in Platelet Count Over Time(Baseline, month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Percentage of Participants Who Maintain Platelet Counts Level Within 12 Months and Every 3 Months Until Month 24(From first time of reaching the level to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Mental Component Summary (MCS) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Percentage of Participants With Worst Post-baseline Value in Functional Assessment of Cancer Therapy-G (GP5)(Baseline to end of treatment visit, assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Bodily Pain (BP) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Role Physical (RP) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Social Functioning (SF) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionaire(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: General Health (GH) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Physical Functioning (PF) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Vitality (VT) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Functional Assessment of Cancer Therapy- Thrombocytopenia (FACT-Th6) Questionnaire(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Role Emotional (RE) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Overall Change of Treatment Satisfaction Using Treatment Satisfaction Questionnaire (TSQM-9)(Baseline to month 12 (End of Treatment Visit for non-responders) and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Mental Health (MH) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)
- Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Physical Component Summary (PCS) Score(Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders)