Thrombotic Thrombocytopenic Purpura MedDRA version: 20.0 Level: PT Classification code 10043648 Term: Thrombotic thrombocytopenic purpura System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: Platelet count =100 × 10^9/L. Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30 × 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of caplacizumab in combination with immunosuppressive therapy (IST) without therapeutic plasma exchange (TPE) in adults with immune mediated thrombotic thrombocytopenic purpura (iTTP);Secondary Objective: To evaluate: - the need for therapeutic plasma exchange in adult participants with an episode of iTTP treated with caplacizumab and IST - the safety of caplacizumab in combination with IST without 1st line TPE in adults with iTTP - the effect of treatment with caplacizumab and IST without 1st line TPE on clinical response - the effect of treatment with caplacizumab and IST without 1st line TPE on restoring platelet counts - the effect of treatment with caplacizumab and IST without 1st line TPE on refractory disease - the effect of treatment with caplacizumab and IST without 1st line TPE on clinically relevant iTTP-related events consisting of iTTP-related mortality - the effect of treatment with caplacizumab and IST without 1st line TPE on clinically relevant iTTP-related events consisting of exacerbation of iTTP - the effect of treatment with caplacizumab and IST without 1st-line TPE on clinically relevant iTTP-related events consisting of relapse of iTTP ;Primary end point(s): Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE); Remission is defined as sustained Clinical Response (sustained platelet count =150 × 10^9/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) 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.;Timepoint(s) of evaluation of this end point: Overall study period from day 1 to day 168 (treatment period + 12 wee | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of participants achieving Remission 2. Proportion of participants who require TPE 3. The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) 4. Proportion of participants achieving Clinical Response; Clinical Response is defined as sustained platelet count =150 × 10^9/L and LDH 1.5 × ULN) despite 5 days of treatment 8. Proportion of participants with TTP-related death 9. Proportion of participants with TTP-related death 10. Proportion of participants with a clinical exacerbation of iTTP; Clinical Exacerbation is defined as after a Clinical Response and before a Clinical Remission, platelet count decreases to <150 × 10^9/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping TPE or anti vWF therapy. 11. Proportion of participants with a clinical exacerbation of iTTP 12. Proportion of participants with a clinical relapse of iTTP; Clinical Relapse is defined as after a Clinical Remission, platelet count decreases to <150 × 10^9/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A Clinical Relapse must be confirmed by documentation of severe ADAMTS13 deficiency (<10%). 13. Proportion of participants with a clinical relapse of iTTP;Timepoint(s) of evaluation of this end point: 1. Overall study period from day 1 to day 168 2. On-treatment period from day 1 to day 84 3. Treatment-emergent (TE) period from day 1 to day 112 4. On-treatment period from day 1 to day 84 5. Overall study period from day 1 to day 168 6. From day 1 to day 168 7. On-treatment period from day 1 to day 84 8. On-treatment period from day 1 to day 84 9. Overall study period from day 1 to day 168 10. On-treatment period from day 1 to day 84 11. Overall study period from day 1 to day 168 12. On-treatment period from day 1 to day 84 13. O | — |
Countries
Austria, Belgium, Canada, Czechia, Czech Republic, France, Germany, Greece, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Study Unit
Sanofi-Aventis Deutschland GmbH
Outcome results
None listed