Back to resultsEfficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult aTTP (CAPLAVIE)
Primary Purpose
Thrombotic Thrombocytopenic Purpura, Acquired
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Caplacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura, Acquired
Eligibility Criteria
Inclusion Criteria:
- Adult patients ≥ 18 years;
- Clinical diagnosis of aTTP based on standard clinical and laboratory criteria (French Score ≥ 2): i.e., thrombotic microangiopathy syndrome with platelet count ≤ 30 G/L and serum creatinine ≤ 200 μmol/L; severe ADAMTS13 deficiency is not a requirement for inclusion of patients with a French score of 2 [31];
- Patient having read and understood the information letter and signed the Informed Consent Form. If the patient is unable to express his consent, the consent will be signed by his representative ((1) the trusted person, or failing that, (2) a family member, or (3) a close relative of the person concerned). In this case, consent to continue the study will subsequently be requested from the patient (article L1122-1-1 of the CSP);
- Patient affiliated with, or beneficiary of a social security (national health insurance) plan;
For women:
Women of childbearing potential :
- Effective contraception according to WHO definition (estrogen-progestin or intrauterine device or tubal ligation) since at least 1 month and;
- Negative blood pregnancy test;
- Women surgically sterile (absence of ovaries and/or uterus);
- Postmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit).
Exclusion Criteria:
- Platelet count > 100 G/L;
- Patients with a French score < 2 (a serum creatinine level > 200 μmol/L +/- associated with a platelet count > 30 G/L), in order to exclude possible cases of atypical hemolytic uremic syndrome;
- Known other causes of cytopenias and/or organ failure including but not limited to: uncontrolled cancer, chemotherapy, transplant, drugs, HIV at AIDS stage;
- Pregnant women (positive result from a blood pregnancy test) or patients with an imminent project of pregnancy; breastfeeding women (due to lack of pharmacological data for caplacizumab during pregnancy and breastfeeding);
- Congenital TTP;
- Clinically significant active bleeding or high risk of bleeding (excluding thrombocytopenia);
- Chronic treatment with anticoagulant that cannot be interrupted safely, including but not limited to: vitamin K antagonists, direct oral anticoagulant, low molecular weight heparin or heparin;
- Malignant hypertension;
- Contra-indication to CABLIVI 10 mg powder and solvent for solution for injection: hypersensitivity to caplacizumab or to any of the excipients;
- Contra-indication to PE treatment;
- Contra-indication to corticosteroid (= ((methyl)prednisone or (methyl)prednisolone)) or excipients;
- Contra-indication to rituximab or excipients and to its premedication;
- Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision);
- Participation in another drug interventional clinical trial within 30 days prior to inclusion and during the study.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Caplacizumab
Arm Description
All patients in the study are aTTP and needs to be treated by caplacizumab. The duration of this treatment will be evaluated through the ADAMTS 13 activity.
Outcomes
Primary Outcome Measures
To evaluate the feasibility of a personalized caplacizumab regimen in aTTP based on ADAMTS13 activity monitoring assessed by a composite criteria including mortality, refractoriness and/or exacerbation at 30 days post-PE treatment
composite endpoint defined by the occurrence of at least one the following events during the 30 days post-PE treatment: death, refractoriness or exacerbation.
Secondary Outcome Measures
Response to treatment (platelet count recovery)
to platelet count recovery (as defined by a platelet count ≥ 150 G/L with a subsequent interruption of daily PE within 5 days)
Durable remission achievement
Occurrence of durable remission achievement (platelet count ≥ 150 G/L for ≥ 30 consecutive days following PE interruption);
Mortality at D90 post-PE treatment
Occurrence of death within 90 days post-PE treatment
Refractoriness at D30 post-PE treatment
Occurrence of refractoriness at D30 post-PE treatment;
Exacerbation at D30 post-PE treatment
Occurrence of exacerbations at D30 post-PE treatment
Duration of plasma exchange (PE) treatment and the associated plasma volumes
Duration of daily PE with the corresponding plasma volume
Duration of plasma exchange (PE) treatment and the associated plasma
Total number of PE and the corresponding plasma volume during the full study drug treatment period
Occurrence of neurological sequelae treatment
Neurological assessment based on Rankin score
Evaluate the Quality of life
Quality of life based on global post-traumatic score (PCL-S SCALE) at baseline, D90 post-PE treatment
Evaluate the cost of the strategy
Costs of the patients' management (Direct hospital medical expenses, Suppléments, direct costs of home care, caplacizumab injections, rehospitalizations) of patients treated with the regimen according to the study
To perform a safety analysis
Occurrence of AE and SAE during the study
Occurrence of cognitive sequelae treatment
Cognitive assessment based on MMS score
Full Information
NCT ID
NCT04720261
First Posted
January 12, 2021
Last Updated
January 19, 2021
Sponsor
University Hospital, Rouen
1. Study Identification
Unique Protocol Identification Number
NCT04720261
Brief Title
Efficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult aTTP
Acronym
CAPLAVIE
Official Title
Efficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult Acquired Thrombotic Thrombocytopenic Purpura: A Phase II, Multicenter Non-inferiority Single-arm Study.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 1, 2021 (Anticipated)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
October 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Rouen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of the study is to evaluate the efficacy of a personalized caplacizumab regimen based on ADAMTS13 activity monitoring in adult acquired thrombotic thrombocytopenic purpura (aTTP): This study is a phase II, prospective, multicenter non-inferiority single-arm study.
Detailed Description
ADAMTS13 activity will be evaluated on day 7 after the end of daily PE and every 7 days until ADAMTS13 activity ≥ 20% is reached. In case of persistent severe ADAMTS13 deficiency (≤ 20%), caplacizumab administration could be extended for a maximum of 58 days after the end of the daily PE period and should be accompanied by an adjusted immunosuppressive therapy as needed. This duration is in accordance with the HERCULES study protocol and its SmPC.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura, Acquired
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Experimental, prospective, non-comparative, multicentric national study
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Caplacizumab
Arm Type
Other
Arm Description
All patients in the study are aTTP and needs to be treated by caplacizumab. The duration of this treatment will be evaluated through the ADAMTS 13 activity.
Intervention Type
Drug
Intervention Name(s)
Caplacizumab
Intervention Description
Analyse of ADAMTS13 activity in patients with aTTP treated with Caplacizumab in order to help adapting the treatment with caplacizumab in TTP patients
Primary Outcome Measure Information:
Title
To evaluate the feasibility of a personalized caplacizumab regimen in aTTP based on ADAMTS13 activity monitoring assessed by a composite criteria including mortality, refractoriness and/or exacerbation at 30 days post-PE treatment
Description
composite endpoint defined by the occurrence of at least one the following events during the 30 days post-PE treatment: death, refractoriness or exacerbation.
Time Frame
30 days post-PE treatment
Secondary Outcome Measure Information:
Title
Response to treatment (platelet count recovery)
Description
to platelet count recovery (as defined by a platelet count ≥ 150 G/L with a subsequent interruption of daily PE within 5 days)
Time Frame
30 days post-PE treatment
Title
Durable remission achievement
Description
Occurrence of durable remission achievement (platelet count ≥ 150 G/L for ≥ 30 consecutive days following PE interruption);
Time Frame
90 days post-PE treatment
Title
Mortality at D90 post-PE treatment
Description
Occurrence of death within 90 days post-PE treatment
Time Frame
90 days post-PE treatment
Title
Refractoriness at D30 post-PE treatment
Description
Occurrence of refractoriness at D30 post-PE treatment;
Time Frame
Day 30 post-PE treatment
Title
Exacerbation at D30 post-PE treatment
Description
Occurrence of exacerbations at D30 post-PE treatment
Time Frame
Day 30 post-PE treatment
Title
Duration of plasma exchange (PE) treatment and the associated plasma volumes
Description
Duration of daily PE with the corresponding plasma volume
Time Frame
30 days
Title
Duration of plasma exchange (PE) treatment and the associated plasma
Description
Total number of PE and the corresponding plasma volume during the full study drug treatment period
Time Frame
30 days
Title
Occurrence of neurological sequelae treatment
Description
Neurological assessment based on Rankin score
Time Frame
Day 90 post-PE treatment
Title
Evaluate the Quality of life
Description
Quality of life based on global post-traumatic score (PCL-S SCALE) at baseline, D90 post-PE treatment
Time Frame
Day 90 post-PE treatment
Title
Evaluate the cost of the strategy
Description
Costs of the patients' management (Direct hospital medical expenses, Suppléments, direct costs of home care, caplacizumab injections, rehospitalizations) of patients treated with the regimen according to the study
Time Frame
Day 90 post-PE treatment
Title
To perform a safety analysis
Description
Occurrence of AE and SAE during the study
Time Frame
90 days post-PE treatment
Title
Occurrence of cognitive sequelae treatment
Description
Cognitive assessment based on MMS score
Time Frame
Day 90 post-PE treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients ≥ 18 years;
Clinical diagnosis of aTTP based on standard clinical and laboratory criteria (French Score ≥ 2): i.e., thrombotic microangiopathy syndrome with platelet count ≤ 30 G/L and serum creatinine ≤ 200 μmol/L; severe ADAMTS13 deficiency is not a requirement for inclusion of patients with a French score of 2 [31];
Patient having read and understood the information letter and signed the Informed Consent Form. If the patient is unable to express his consent, the consent will be signed by his representative ((1) the trusted person, or failing that, (2) a family member, or (3) a close relative of the person concerned). In this case, consent to continue the study will subsequently be requested from the patient (article L1122-1-1 of the CSP);
Patient affiliated with, or beneficiary of a social security (national health insurance) plan;
For women:
Women of childbearing potential :
Effective contraception according to WHO definition (estrogen-progestin or intrauterine device or tubal ligation) since at least 1 month and;
Negative blood pregnancy test;
Women surgically sterile (absence of ovaries and/or uterus);
Postmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit).
Exclusion Criteria:
Platelet count > 100 G/L;
Patients with a French score < 2 (a serum creatinine level > 200 μmol/L +/- associated with a platelet count > 30 G/L), in order to exclude possible cases of atypical hemolytic uremic syndrome;
Known other causes of cytopenias and/or organ failure including but not limited to: uncontrolled cancer, chemotherapy, transplant, drugs, HIV at AIDS stage;
Pregnant women (positive result from a blood pregnancy test) or patients with an imminent project of pregnancy; breastfeeding women (due to lack of pharmacological data for caplacizumab during pregnancy and breastfeeding);
Congenital TTP;
Clinically significant active bleeding or high risk of bleeding (excluding thrombocytopenia);
Chronic treatment with anticoagulant that cannot be interrupted safely, including but not limited to: vitamin K antagonists, direct oral anticoagulant, low molecular weight heparin or heparin;
Malignant hypertension;
Contra-indication to CABLIVI 10 mg powder and solvent for solution for injection: hypersensitivity to caplacizumab or to any of the excipients;
Contra-indication to PE treatment;
Contra-indication to corticosteroid (= ((methyl)prednisone or (methyl)prednisolone)) or excipients;
Contra-indication to rituximab or excipients and to its premedication;
Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision);
Participation in another drug interventional clinical trial within 30 days prior to inclusion and during the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ygal BENHAMOU
Phone
0232889274
Email
ygal.benhamou@chu-rouen.fr
12. IPD Sharing Statement
Plan to Share IPD
No
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Efficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult aTTP
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