Clinical trial NCT04720261: Efficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult aTTP
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Thrombotic Thrombocytopenic Purpura, Acquired
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2021-01-22
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental, prospective, non-comparative, multicentric national study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 30 days post-PE treatment
Secondary outcomes:
measure: Response to treatment (platelet count recovery)
timeFrame: 30 days post-PE treatment
measure: Durable remission achievement
timeFrame: 90 days post-PE treatment
measure: Mortality at D90 post-PE treatment
timeFrame: 90 days post-PE treatment
measure: Refractoriness at D30 post-PE treatment
timeFrame: Day 30 post-PE treatment
measure: Exacerbation at D30 post-PE treatment
timeFrame: Day 30 post-PE treatment
measure: Duration of plasma exchange (PE) treatment and the associated plasma volumes
timeFrame: 30 days
measure: Duration of plasma exchange (PE) treatment and the associated plasma
timeFrame: 30 days
measure: Occurrence of neurological sequelae treatment
timeFrame: Day 90 post-PE treatment
measure: Evaluate the Quality of life
timeFrame: Day 90 post-PE treatment
measure: Evaluate the cost of the strategy
timeFrame: Day 90 post-PE treatment
measure: To perform a safety analysis
timeFrame: 90 days post-PE treatment
measure: Occurrence of cognitive sequelae treatment
timeFrame: Day 90 post-PE treatment
Other outcomes:
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Study officials:
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