Efficacy of a Personalized Caplacizumab Regimen Based on ADAMTS13 Activity Monitoring in Adult aTTP

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.

Sponsors

Lead Sponsor: University Hospital, Rouen

Source University Hospital, Rouen
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.

Overall Status Not yet recruiting
Start Date 2021-05-01
Completion Date 2023-10-01
Primary Completion Date 2023-10-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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 30 days post-PE treatment
Secondary Outcome
Measure Time Frame
Response to treatment (platelet count recovery) 30 days post-PE treatment
Durable remission achievement 90 days post-PE treatment
Mortality at D90 post-PE treatment 90 days post-PE treatment
Refractoriness at D30 post-PE treatment Day 30 post-PE treatment
Exacerbation at D30 post-PE treatment Day 30 post-PE treatment
Duration of plasma exchange (PE) treatment and the associated plasma volumes 30 days
Duration of plasma exchange (PE) treatment and the associated plasma 30 days
Occurrence of neurological sequelae treatment Day 90 post-PE treatment
Evaluate the Quality of life Day 90 post-PE treatment
Evaluate the cost of the strategy Day 90 post-PE treatment
To perform a safety analysis 90 days post-PE treatment
Occurrence of cognitive sequelae treatment Day 90 post-PE treatment
Enrollment 125
Condition
Intervention

Intervention Type: Drug

Intervention Name: Caplacizumab

Description: Analyse of ADAMTS13 activity in patients with aTTP treated with Caplacizumab in order to help adapting the treatment with caplacizumab in TTP patients

Arm Group Label: Caplacizumab

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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

100 Years

Healthy Volunteers:

No

Overall Contact

Last Name: Ygal BENHAMOU

Phone: 0232889274

Email: [email protected]

Verification Date

2021-01-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Caplacizumab

Type: Other

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.

Acronym CAPLAVIE
Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Intervention Model Description: Experimental, prospective, non-comparative, multicentric national study

Primary Purpose: Treatment

Masking: None (Open Label)

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