An Open-label, Single-arm, Multicenter Pilot Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Pegcetacoplan in Patients With Transplant-associated Thrombotic Microangiopathy (TA-TMA) After Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 14
- 主要终点
- Pegcetacoplan Pharmacokinetic (PK) Parameter Area Under the Curve Limited to the End of Dosing Interval (AUC0-tau)
研究概览
简要总结
The purpose of the study was to assess pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of pegcetacoplan in patients with TA-TMA after HSCT.
详细描述
This was a pilot study, and the sample size was based on practical rather than statistical aspects.
A total of 12 patients were to be included and treated in the study. With 12 patients included, it was estimated that 9 patients would complete at least 4 weeks of treatment, which is deemed sufficient to characterize the PK of pegcetacoplan in patients with TA-TMA to an appropriate precision. In addition, 12 patients would provide a 72 % probability to observe a response rate of at least 8 responders of the 12 patients recruited (assuming the true response rate is 70 %).
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
- •Male and female patients aged ≥ 18 years at the time of informed consent form (ICF) signature.
- •Received allogeneic HSCT.
- •Diagnosis of TA-TMA established, as per laboratory markers indicating TMA.
- •Have a diagnosis of TA-TMA that persists despite initial management of any triggering condition.
- •Have random urine protein/creatinine ratio (rUPCR) ≥ 1 mg/mg.
- •Women of childbearing potential, defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative serum pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last investigational medicinal product (IMP) dose.
- •Note: Postmenopausal is defined as having had 12 consecutive months with no menses without an alternative medical cause.
- •Men must agree to the following for the duration of the study and 8 weeks after their last dose of IMP:
- •Avoid fathering a child.
- •Use protocol-defined methods of contraception.
- •Refrain from donating sperm.
- •Patient and/or legally authorized representative must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
排除标准
- •Positive direct Coombs test.
- •Known familial or acquired ADAMTS13 deficiency.
- •Known Shiga toxin-related hemolytic uremic syndrome.
- •Known bone marrow or graft failure.
- •Diagnosis of disseminated intravascular coagulation.
- •Diagnosis of veno-occlusive disease (VOD).
- •Active GI bleeding (hematemesis or hematochezia) at baseline.
- •Body weight < 30 kg and > 100 kg.
- •Uncontrolled systemic bacterial or fungal infection, presence or suspicion of sepsis.
- •Previously or currently treated with a complement inhibitor (approved or investigational).
- •Pregnancy or breastfeeding.
- •Positive human immunodeficiency virus antibody at screening or documented in pre-HSCT medical record.
- •Hepatitis C virus detectable by polymerase chain reaction at screening or documented in pre-HSCT medical record.
- •Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in pre-HSCT medical record. Eligible patients who are chronic active carriers (≤ 1000 IU/mL) must receive prophylactic antiviral treatment (e.g., entecavir, tenofovir, lamivudine) according to local country guidelines.
- •Known or suspected hereditary fructose intolerance.
- •Hypersensitivity to pegcetacoplan or any of its excipients.
- •Inability to cooperate with study procedures or any condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
研究组 & 干预措施
Pegcetacoplan
sterile solution in stoppered glass vial given as infusion, for a total treatment duration of 12 to 16 weeks.
干预措施: Pegcetacoplan (Drug)
结局指标
主要结局
Pegcetacoplan Pharmacokinetic (PK) Parameter Area Under the Curve Limited to the End of Dosing Interval (AUC0-tau)
时间窗: Week 1
Area under the concentration-time curve limited to the end of the dosing interval. The samples included in the calculation of AUC0-tau were collected at the following times: on dosing Days 1, 3 and 5, PK samples were taken up to 30 minutes pre-dose and at 15 minutes (± 5 min), 30 minutes (± 5 min), 1 hour (± 10 min), 4 hours (± 10 min), 8 hours (± 30 min), and 24 hours (± 30 min) post-dose as well as on Day 8 pre-dose.
Pegcetacoplan PK Parameter Maximal Serum Concentration (Cmax)
时间窗: Week 1
Maximum observed serum concentration. Determined using the samples collected post-dose on dosing Days 1, 3 and 5.
Pegcetacoplan PK Parameter Time to Cmax (Tmax)
时间窗: Week 1
Time of maximum measured serum concentration. Determined using the samples collected post-dose on dosing Days 1, 3 and 5.
Pegcetacoplan PK Parameter Observed Serum Concentration Pre-dose (Ctrough)
时间窗: Week 1 up to Week 14
Observed serum concentration pre-dose. From Day 8 (Week 1) and onwards, PK samples were taken pre-dose at each visit.
次要结局
- Absolute Levels and Change From Baseline in sC5b-9(Week 24)
- Absolute Levels and Change From Baseline in C3a(Week 24)
- Absolute Levels and Change From Baseline in C3(Week 24)
- Absolute Levels and Change From Baseline in Bb(Week 24)
- Absolute Levels and Change From Baseline in C4a(Week 24)
- Number of Participants Reaching Clinical Response at Week 12(Week 12)
- Number of Participants Reaching TMA Response at Week 12(Week 12)
- Absolute Levels and Change From Baseline in Classical Pathway (CH50)(Week 24)
- Absolute Levels and Change From Baseline in Alternative Pathway (AH50)(Week 24)
- Duration of Clinical Response(From the first observed clinical response until the response criteria is no longer fulfilled or until end of study, up to 24 weeks)
- Duration of TMA Response(From the first observed TMA response until the response criteria is no longer fulfilled or until end of study, up to 24 weeks)
- TA-TMA Relapse at Week 24(Week 24)
- Number of Participants Reaching Clinical Response at Week 24(Week 24)
- Number of Participants Reaching TMA Response at Week 24(Week 24)
- Overall Survival at Day 100(Day 100 from diagnosis)
- Overall Survival at Week 24(Week 24 from treatment start)
- Time to Clinical Response(From treatment start to first documentation of attainment of a clinical response, up to 24 weeks)
- Time to TMA Response(From treatment start to first documentation of attainment of a TMA response, up to 24 weeks)