Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Interventions
- Registration Number
- NCT05468320
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
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 2.
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Caplacizumab & immunosuppressive therapy without 1st-line TPE Caplacizumab All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE Caplacizumab & immunosuppressive therapy without 1st-line TPE Corticosteroids All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE Caplacizumab & immunosuppressive therapy without 1st-line TPE anti-CD20 antibody All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE
- Primary Outcome Measures
Name Time Method Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE). Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up) Remission is defined as sustained Clinical Response (sustained platelet count ≥150 x 10\^9/L and lactate dehydrogenase \[LDH\] \<1.5 x upper limit of normal \[ULN\] and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits) with either (a) no TPE and no anti- von Willebrand factor (anti-vWF) therapy for ≥ 30 days (Clinical Remission), or (b) with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) ≥ 50% (Complete ADAMTS13 remission), whichever occurs first
- Secondary Outcome Measures
Name Time Method Proportion of participants achieving Clinical Response Overall study period from day 1 to day 168 Proportion of participants with TTP-related death Overall study period from day 1 to day 168 Proportion of participants achieving Remission Overall study period from day 1 to day 168 Proportion of participants who require TPE On-treatment period from day 1 to day 84 Time to platelet count response From day 1 to day 168 Platelet count response defined as time from start of treatment to initial platelet count ≥150 x 10\^9/L that is sustained for ≥2 days
Proportion of participants refractory to therapy On-treatment period from day 1 to day 84 Refractory to therapy defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts \<50 x10\^9/L and persistently elevated LDH (\>1.5 x ULN) despite 5 days of treatment
Proportion of participants with a clinical relapse of iTTP Overall study period from day 1 to day 168 The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) Treatment-emergent (TE) period from day 1 to day 112 Proportion of participants with a clinical exacerbation of iTTP Overall study period from day 1 to day 168
Trial Locations
- Locations (32)
Investigational Site Number : 3800003
🇮🇹Avellino, Campania, Italy
Investigational Site Number : 3800001
🇮🇹Milano, Lombardia, Italy
Investigational Site Number : 3800006
🇮🇹Genova, Italy
Investigational Site Number : 3800005
🇮🇹Verona, Italy
Investigational Site Number : 3800004
🇮🇹Vicenza, Italy
Investigational Site Number : 3920003
🇯🇵Kurashiki-shi, Okayama, Japan
Investigational Site Number : 3920001
🇯🇵Iruma-gun, Saitama, Japan
Investigational Site Number : 5280002
🇳🇱Amersfoort, Netherlands
Investigational Site Number : 7240001
🇪🇸Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 8260001
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 8260002
🇬🇧Liverpool, United Kingdom
University of Alabama- Site Number : 8400011
🇺🇸Birmingham, Alabama, United States
Johns Hopkins University- Site Number : 8400007
🇺🇸Baltimore, Maryland, United States
Duke University Medical Center Site Number : 8400022
🇺🇸Durham, North Carolina, United States
The Ohio State University Comprehensive Cancer Center - Site Number : 8400001
🇺🇸Columbus, Ohio, United States
University of Utah- Site Number : 8400009
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number : 0400001
🇦🇹Wien, Austria
Investigational Site Number : 0560003
🇧🇪Yvoir, Belgium
Investigational Site Number : 1240001
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 2030001
🇨🇿Brno, Czechia
Investigational Site Number : 2030002
🇨🇿Hradec Kralove, Czechia
Investigational Site Number : 2030003
🇨🇿Praha 2, Czechia
Investigational Site Number : 2500002
🇫🇷Bois Guillaume, France
Investigational Site Number : 2500005
🇫🇷Lille, France
Investigational Site Number : 2500003
🇫🇷Paris, France
Investigational Site Number : 2500001
🇫🇷Paris, France
Investigational Site Number : 2760006
🇩🇪Berlin, Germany
Investigational Site Number : 2760003
🇩🇪Essen, Germany
Investigational Site Number : 2760001
🇩🇪Frankfurt am Main, Germany
Investigational Site Number : 2760004
🇩🇪Hannover, Germany
Investigational Site Number : 2760002
🇩🇪Köln, Germany
Investigational Site Number : 2760007
🇩🇪Leipzig, Germany