An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 51
- 试验地点
- 7
- 主要终点
- Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period
研究概览
简要总结
This is a single group, treatment, Phase 3, open-label, single-arm study to evaluate the efficacy and safety of caplacizumab and immunosuppressive therapy (IST) without firstline therapeutic plasma exchange (TPE) with primary endpoint of remission in male and female participants aged 18 to 80 years with immune-mediated thrombotic thrombocytopenic purpura (iTTP).
The anticipated study duration per participant without a recurrence while on therapy is maximum 24 weeks (ie, approximately 1 day for screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up). Participants will have daily assessments during hospitalization and weekly visits for assessments during ongoing treatment with caplacizumab and IST. There will be 3 outpatient visits for assessments during the follow-up period. There will be two additional follow-up visits for participants who do not have ADAMTS13 activity levels of ≥50% at the time of caplacizumab discontinuation.
详细描述
The anticipated study duration per participant with the presenting episode therefore is a maximum of about 24 weeks (ie, 1 day of screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up).
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by ADAMTS13 testing within 48 hours (2 days).
- •Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- •Is a woman of nonchildbearing potential (WONCBP), OR
- •Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration.
- •Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.
排除标准
- •Platelet count ≥100 x 10^9/L. Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30 x 10^9/L (to exclude possible cases of atypical HUS).
- •Known other causes of thrombocytopenia including but not limited to:
- •Clinical evidence of enteric infection with E. coli 0157 or related organism.
- •Atypical HUS.
- •Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy.
- •Known or suspected sepsis.
- •Diagnosis of disseminated intravascular coagulation. Congenital TTP (known at the time of study entry). Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia).
- •Inherited or acquired coagulation disorders. Malignant arterial hypertension. Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.).
- •Those presenting with severe neurological or cardiac disease. Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy.
- •Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to:
- •vitamin K antagonists.
- •direct-acting oral anticoagulants.
- •heparin or low molecular weight heparin (LMWH).
- •non-steroidal anti-inflammatory molecules other than acetyl salicylic acid. Participants who were previously enrolled in this clinical study (study EFC16521).
- •Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer.
- •Positive result on COVID test.
- •The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Caplacizumab & immunosuppressive therapy without 1st-line TPE
All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody [rituximab or biosimilar]) without first line TPE
干预措施: Caplacizumab (Drug)
Caplacizumab & immunosuppressive therapy without 1st-line TPE
All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody [rituximab or biosimilar]) without first line TPE
干预措施: Corticosteroids (Drug)
Caplacizumab & immunosuppressive therapy without 1st-line TPE
All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody [rituximab or biosimilar]) without first line TPE
干预措施: anti-CD20 antibody (Biological)
结局指标
主要结局
Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period
时间窗: From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Remission was defined as sustained clinical response with either no TPE and no anti- von Willebrand factor (vWF) therapy for \>=30 days (clinical remission) or with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) activity level \>=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count \>=150 × 10\^9/liter (L) and lactate dehydrogenase (LDH) \<1.5 × upper limit of normal (ULN) and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
次要结局
- Percentage of Participants Who Achieved Remission During Overall Study Period(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))
- Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)(From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks))
- Percentage of Participants Who Achieved Clinical Response During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Percentage of Participants Who Achieved Clinical Response During Overall Study Period(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))
- Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura-Related Death During Overall Study Period(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))
- Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))
- Time to Platelet Count Response(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))
- Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)-Related Death During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Percentage of Participants Refractory to Therapy During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period(From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks)
- Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period(From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks))