SOAR, Interventional Phase II Single-arm Study to Assess Efficacy and Safety of Eltrombopag Combined With Cyclosporine as First Line Therapy in Adult Patients With Severe Acquired Aplastic Anemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Overall Hematologic Response Rate by 6 Months
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of eltrombopag in combination with cyclosporine alone as first-line therapy on overall hematologic response
详细描述
This was an interventional phase II, single-arm, multicenter, open-label, study to investigate the efficacy and safety of the combination of eltrombopag and cyclosporine in treatment-naive, adult subjects with severe aplastic anemia (SAA) as first line therapy.
Eligible subjects received eltrombopag and cyclosporine for up to 6 months. Participants who achieved hematologic response any time on or before 6 months were considered as responders; else they were considered as non-responders.
Responders at Month 6 discontinued eltrombopag and started to taper cyclosporine until relapse or Month 24, whichever was early. Responders who relapsed prior to 6 months and non-responders discontinued the treatment at 6 months and were followed-up for 30 days.
Responders who started to taper cyclosporine and relapsed prior to 24 months discontinued cyclosporine and were followed-up for 30 days.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient had signed the Informed Consent (ICF) prior to any screening procedures
- •Patient was male/female ≥18 years old at the time of informed consent and able to swallow a tablet.
- •Patient had SAA characterized by:
- •Bone marrow cellularity <30% (excluding lymphocytes) and
- •At least two of the following (peripheral blood):
- •Absolute neutrophil count <500/µL
- •Platelet count <20,000/µL
- •Absolute reticulocyte count <60,000/µL
- •Normal ECG defined as the following as determined via the mean of a triplicate ECG
- •Resting heart rate: 50-90 bpm
- •QTcF at screening <450 msec (for male patients), ≤460 msec (for female patients)
排除标准
- •Diagnosis of Fanconi anemia.
- •Evidence of a clonal hematologic bone marrow disorder on cytogenetics by central review
- •Prior immunosuppressive therapy with cyclosporine, alemtuzumab, rabbit or horse ATG and thrombopoietin receptor (TPO-R) agonists.
- •Hypersensitivity to eltrombopag or cyclosporine or their components.
- •AST or ALT >3 x ULN.
- •Serum creatinine, total bilirubin, or alkaline phosphatase >1.5 x ULN.
- •Patient with liver cirrhosis.
- •Patients who were human immune deficiency virus (HIV), hepatitis C virus or hepatitis B surface antigen (HBsAg) positive. HCV-RNA negative patients were allowed to be enrolled.
- •Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to consent, be compliant with study procedures, tolerate protocol therapy, or that death within 30 days is likely.
- •Patients with cancer who were not considered cure, were on active chemotherapeutic treatment or who took drugs with hematological effects.
- •Administration of an investigational drug within 30 days or 5 half-lives, whichever was longer, preceding the first dose of study treatment.
- •Pregnancy statements and contraception requirements:
- •Pregnancy or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant (or female partners of male patients), unless they were using highly effective methods of contraception during dosing and for 3 months after stopping medication.
- •Not able to understand the investigation nature of the study or to give informed consent.
- •Clinically significant ECG abnormality including cardiac arrhythmias (e. g. ventricular tachycardia) complete left bundle branch block, high grade atrioventricular block, or inability to determine the QTcF interval on the ECG.
- •Presence of cardiac disease, or family history of idiopathic sudden death or congenital long QT syndrome.
- •Risk factors for Torsades de Pointe including uncorrected hypokalemia or hypomagnesemia, or use of concomitant medication(s) with a known risk to prolong the QT interval that could not be discontinued or replaced by safe alternative medication per www.qtdrugs.org.
- •ECOG performance status of ≥
- •Patients under the age of 40 must be referred for consideration of allogeneic bone marrow transplantation (HSCT) if (human leukocyte antigen) HLA matching had been done and a suitable matched sibling donor was available and the patient was willing to undergo transplantation (i.e. patients who did not have a HLA match or were not medically fit, not willing or unable to undergo transplantation were considered for enrollment).
研究组 & 干预措施
Eltrombopag + cyclosporine
Participants received eltrombopag (orally, 150 mg once daily for non-Asian participants / 100 mg once daily for participants of Asian ancestry) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
干预措施: eltrombopag (Drug)
Eltrombopag + cyclosporine
Participants received eltrombopag (orally, 150 mg once daily for non-Asian participants / 100 mg once daily for participants of Asian ancestry) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
干预措施: Cyclosporine (Drug)
结局指标
主要结局
Overall Hematologic Response Rate by 6 Months
时间窗: Up to 6 months
Overall hematologic response rate by 6 months was defined as the percentage of participants with complete response (CR) or partial response (PR) any time on or before 6 months. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * Absolute neutrophil count (ANC) \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L
次要结局
- Overall Hematologic Response Rate by 3 Months(Up to 3 months)
- Overall Hematologic Response Rate at 12 and 24 Months(12 and 24 months)
- Duration of First Hematologic Response(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Relapse Rate by 6 and 24 Months(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Percentage of Participants With Evolution to Myelodysplasia, Paroxysmal Nocturnal Hemoglobinuria (PNH) and Leukemia(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Percentage of Participants Who Were Red Blood Cells (RBC) Transfusion Independent(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Percentage of Participants Who Were Platelet Transfusion Independent(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Longest Duration of Transfusion Independence (Platelet or RBC)(Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6))
- Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome(Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only))
- Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome(Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only))
- Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome(Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only))
- Pharmacokinetic Parameter- Cmax of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose.)
- Pharmacokinetic Parameter-AUClast of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose)
- Pharmacokinetic Parameter- AUCtau of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose)
- Pharmacokinetic Parameter- Ctrough of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose)
- Pharmacokinetic Parameter- Tmax of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose)
- Pharmacokinetic Parameter- CLss/F of Eltrombopag When Combined With Cyclosporine(Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose)