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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Thrombotic Thrombocytopenic Purpura, Acquired
• Intervention / Treatment: Drug: Caplacizumab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 125
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ygal BENHAMOU; Phone Number: 0232889274; Email: ygal.benhamou@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Caplacizumab; 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.	Drug: Caplacizumab; Analyse of ADAMTS13 activity in patients with aTTP treated with Caplacizumab in order to help adapting the treatment with caplacizumab in TTP patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	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	composite endpoint defined by the occurrence of at least one the following events during the 30 days post-PE treatment: death, refractoriness or exacerbation.	30 days post-PE treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	30 days post-PE treatment
Durable remission achievement	Occurrence of durable remission achievement (platelet count ≥ 150 G/L for ≥ 30 consecutive days following PE interruption);	90 days post-PE treatment
Mortality at D90 post-PE treatment	Occurrence of death within 90 days post-PE treatment	90 days post-PE treatment
Refractoriness at D30 post-PE treatment	Occurrence of refractoriness at D30 post-PE treatment;	Day 30 post-PE treatment
Exacerbation at D30 post-PE treatment	Occurrence of exacerbations at D30 post-PE treatment	Day 30 post-PE treatment
Duration of plasma exchange (PE) treatment and the associated plasma volumes	Duration of daily PE with the corresponding plasma volume	30 days
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	30 days
Occurrence of neurological sequelae treatment	Neurological assessment based on Rankin score	Day 90 post-PE treatment
Evaluate the Quality of life	Quality of life based on global post-traumatic score (PCL-S SCALE) at baseline, D90 post-PE treatment	Day 90 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	Day 90 post-PE treatment
To perform a safety analysis	Occurrence of AE and SAE during the study	90 days post-PE treatment
Occurrence of cognitive sequelae treatment	Cognitive assessment based on MMS score	Day 90 post-PE treatment

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 19, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
• Other Study ID Numbers: 2019/0408/HP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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