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.
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.
Brief Title
Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
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).
Completion Date
Completion Date Type
Actual
Conditions
Thrombotic Thrombocytopenic Purpura
Eligibility 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:
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.
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.
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.
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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT05468320
Org Class
Industry
Org Full Name
Sanofi
Org Study Id
EFC16521
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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
Outcome Measure
Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).
Outcome Time Frame
Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)
Secondary Ids
Secondary Id
U1111-1244-0426
Secondary Id
2024-513262-19
Secondary Id
2022-001177-31
Secondary Outcomes
Outcome Time Frame
Overall study period from day 1 to day 168
Outcome Measure
Proportion of participants achieving Remission
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants who require TPE
Outcome Time Frame
Treatment-emergent (TE) period from day 1 to day 112
Outcome Measure
The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Outcome Description
Clinical Response is defined as sustained platelet count ≥150 x 10\^9/L and LDH \<1.5 x ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants achieving Clinical Response
Outcome Time Frame
Overall study period from day 1 to day 168
Outcome Measure
Proportion of participants achieving Clinical Response
Outcome Description
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
Outcome Time Frame
From day 1 to day 168
Outcome Measure
Time to platelet count response
Outcome Description
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
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants refractory to therapy
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants with TTP-related death
Outcome Time Frame
Overall study period from day 1 to day 168
Outcome Measure
Proportion of participants with TTP-related death
Outcome Description
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.
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants with a clinical exacerbation of iTTP
Outcome Time Frame
Overall study period from day 1 to day 168
Outcome Measure
Proportion of participants with a clinical exacerbation of iTTP
Outcome Description
Clinical Relapse is defined as after a Clinical Remission, platelet count decreases to \<150 x 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%).
Outcome Time Frame
On-treatment period from day 1 to day 84
Outcome Measure
Proportion of participants with a clinical relapse of iTTP
Outcome Time Frame
Overall study period from day 1 to day 168
Outcome Measure
Proportion of participants with a clinical relapse of iTTP
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO