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).
Categories
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 was defined as sustained clinical response with either no TPE and no anti- von Willebrand factor (vWF) therapy for \>=30 days (clinical remission) or with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) activity level \>=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count \>=150 × 10\^9/liter (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.
Outcome Measure
Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Secondary Ids
Secondary Id
U1111-1244-0426
Secondary Id
2024-513262-19
Secondary Id
2022-001177-31
Secondary Outcomes
Outcome Description
Remission was defined as sustained clinical response with either no TPE and no anti- vWF therapy for \>=30 days (clinical remission) or with ADAMTS13 activity level \>=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count \>=150 × 10\^9/L and LDH \<1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Percentage of Participants Who Achieved Remission During Overall Study Period
Outcome Description
TPE was a procedure in which blood of the participant was passed through a medical device which separated out plasma from other components of blood and the participant's plasma was removed and replaced with a replacement solution such as colloid solution (example, albumin and/or plasma) or a combination of crystalloid/colloid solution. TPE replenishes the ADAMTS13 enzyme and removes anti-ADAMTS13 antibodies, and ultra-large von Willebrand factor multimers gradually from the circulation.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period
Outcome Description
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period. SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect, or any other situation where medical or scientific judgment of investigator were exercised. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks)
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)
Outcome Description
Clinical response was defined as sustained platelet count \>=150 × 10\^9/L and LDH \<1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants Who Achieved Clinical Response During On-Treatment Period
Outcome Description
Clinical response was defined as sustained platelet count \>=150 × 10\^9/L and LDH \<1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Percentage of Participants Who Achieved Clinical Response During Overall Study Period
Outcome Description
Time to platelet count response was defined as time from start of study treatment to initial platelet count \>=150 × 10\^9/L that was sustained for \>=2 days.
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Time to Platelet Count Response
Outcome Description
Refractory to therapy was defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts \<50 × 10\^9/L and persistently elevated LDH (\>1.5 × ULN) despite 5 days of treatment during the on-treatment period.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants Refractory to Therapy During On-Treatment Period
Outcome Description
Percentage of participants with iTTP-related death during on-treatment period are reported.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)-Related Death During On-Treatment Period
Outcome Description
Percentage of participants with iTTP-related death during overall study period are reported.
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura-Related Death During Overall Study Period
Outcome Description
Clinical exacerbation was defined as after a clinical response and before a clinical remission, platelet count decreased 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.
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period
Outcome Description
Clinical exacerbation was defined as after a clinical response and before a clinical remission, platelet count decreased 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.
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period
Outcome Description
Clinical relapse was defined as after a clinical remission, platelet count decreased 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 had to be confirmed by documentation of severe ADAMTS13 deficiency (\<10%).
Outcome Time Frame
From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Outcome Measure
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period
Outcome Description
Clinical relapse was defined as after a clinical remission, platelet count decreased 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 had to be confirmed by documentation of severe ADAMTS13 deficiency (\<10%).
Outcome Time Frame
From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Outcome Measure
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period
See Also Links
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
Categories Mesh Debug
Blood Disorders --- BLOOD COAGULATION DISORDERS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood Disorders --- BLOOD PLATELET DISORDERS
Blood Disorders --- HEMORRHAGE
MeSH Terms
PURPURA, THROMBOTIC THROMBOCYTOPENIC
PURPURA, THROMBOCYTOPENIC
PURPURA
BLOOD COAGULATION DISORDERS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
THROMBOTIC MICROANGIOPATHIES
THROMBOCYTOPENIA
BLOOD PLATELET DISORDERS
CYTOPENIA
THROMBOPHILIA
HEMORRHAGE
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
SKIN MANIFESTATIONS
SIGNS AND SYMPTOMS
CAPLACIZUMAB
ADRENAL CORTEX HORMONES
PREDNISONE
PREDNISOLONE
RITUXIMAB
BIOSIMILAR PHARMACEUTICALS
HORMONES
HORMONES, HORMONE SUBSTITUTES, AND HORMONE ANTAGONISTS
PREGNADIENEDIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
PREGNADIENETRIOLS
ANTIBODIES, MONOCLONAL, MURINE-DERIVED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
BIOLOGICAL PRODUCTS
COMPLEX MIXTURES