Thrombotic Thrombocytopenic Purpura
Conditions
Interventions
Drug: Caplacizumab
Lyophilized powder for solution for injection.
Drug: Corticosteroids
Solution for injection or Tablet
Biological: anti-CD20 antibody
Solution for injection, Other Name: rituximab
Sponsors
Obara Kentaro
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.
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - Platelet count >=100 x 10^9/L. - Serum creatinine level >2.26 mg/dL (200 micro mol/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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE). [Time Frame baseline: 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] = 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
| Measure | Time frame |
|---|---|
| 1. Proportion of participants achieving Remission [Time Frame baseline:Overall study period ] 2. Proportion of participants who require TPE [Time Frame baseline:On-treatment period from day 1 to day 84] 3. The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) [Time Frame baseline:Treatment-emergent (TE) period from day 1 to day 112] 4. Proportion of participants achieving Clinical Response [Time Frame baseline:On-treatment period from day 1 to day 84] Clinical Response is defined as sustained platelet count >= 150 x 10^9/L and LDH = 150 x 10^9/L that is sustained for >= 2 days 7. Proportion of participants refractory to therapy [Time Frame baseline: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 1.5 x ULN) despite 5 days of treatment 8. Proportion of participants with TTP-related death [Time Frame baseline:On-treatment period from day 1 to day 84] 9. Proportion of participants with TTP-related death [Time Frame baseline:Overall study period from day 1 to day 168] 10. Proportion of participants with a clinical exacerbation of iTTP [Time Frame baseline:On-treatment period from day 1 to day 84] Clinical Exacerbation is defined as after a Clinical Response and before a Clinical Remission, platelet count decreases to <150 x 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 [Time Frame baseline:Overall study period from day 1 to day 168] 12. Proportion of participants with a clinical relapse of iTTP [Time Frame baseline:On-treatment period from day 1 to day 84] Clinical Relapse is defined as after a Clinical Remission, platelet count decreases to <150 x 10^9/L (with other causes of thromboc | — |
Countries
Austria, Belgium, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed