Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
Investigational Treatment for Immune-mediated Thrombotic Thrombocytopenic Purpura
Study Overview
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.
Study Details
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).
Eligibility Criteria
You may be eligible for this study if you meet the following criteria:
- Conditions: Thrombotic Thrombocytopenic Purpura
-
Age: 18 years - 80 years
-
Gender: All
Inclusion Criteria:
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.
Exclusion Criteria:
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.
This study investigates the effectiveness and safety of an investigational medication and immunosuppressive therapy in treating adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) without the initial use of therapeutic plasma exchange. This study seeks to understand if remission can be achieved in participants aged 18 to 80 years.
Participants in this study will undergo daily assessments during hospitalization and weekly visits during the ongoing treatment phase with the investigational medication and immunosuppressive therapy. After the treatment phase, there will be three outpatient visits for follow-up assessments, with additional follow-up visits for participants whose ADAMTS13 activity levels remain low. The study procedures aim to monitor the effectiveness and safety of the treatment regimen.
- Who can participate: Adults aged 18 to 80 years with a clinical diagnosis of iTTP, confirmed by ADAMTS13 testing, may participate. Women must not be pregnant or breastfeeding and must agree to use contraception if of childbearing potential. Men must also agree to use contraception if they have partners of childbearing potential.
- Study details: Participants will receive an investigational medication and immunosuppressive therapy without initial plasma exchange. The study includes regular assessments to track treatment response and safety. Participants will have follow-up visits to monitor their health after the treatment phase.
- Study timelines and visits: The study will last a maximum of 24 weeks. The study requires 3 outpatient visits for assessments during the follow-up period.
