Platelet Response to Caplacizumab in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura (PREDICT2020)

The interpretation of platelet counts has to be revaluated in the light of caplacizumab. By effectively blocking platelet binding sites on VWF-multimers, the nanobody leads to a rapid normalization of the platelet count within 3 to 4 days. Most importantly, caplacizumab uncouples platelet counts from ADAMTS13 activity and thereby launches unprecedented thrombocyte dynamics, with potential pitfalls for over- and undertreatment.

A relevant number of patients responds to caplacizumab with a brisk increase in platelet count, followed by a marked dip of platelets (patient on the left). This may mislead treating physicians into re-intensifying therapy, with a respective risk for adverse side-effects and complications. Taken together, these observations call for reliable descriptions and the identification of predictive parameters to predict the platelet response upon administration of caplacizumab in a large patient cohort. Here, PREDICT-2020 is designed as a retrospective study to specifically address the following aspects:

• Identifying and describing clusters of platelet responses to caplacizumab
• Identifying potential pitfalls for treating physicians
• Predicting the individual thrombocyte response
• Correlating platelet responses with individual patient outcome

Study Overview

• Status: Recruiting
• Conditions: Acquired Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Cablivi

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Lucas Kühne, MD; Phone Number: +49 221 478 36990; Email: lucas.kuehne@uk-koeln.de
• Study Contact Backup: Name: Linus Völker, MD; Phone Number: +49 221 478 36990; Email: linus.voelker@uk-koeln.de

Study Locations

• Germany
  • Cologne, Germany
    • Recruiting
    • University Hospital of Cologne
    • Sub-Investigator: Linus Völker, MD
    • Contact: Lucas Kühne, MD; Phone Number: +49 221 478 36990; Email: lucas.kuehne@uk-koeln.de
    • Contact: Linus Völker, MD; Phone Number: +49 221 478 36990; Email: linus.voelker@uk-koeln.de
    • Principal Investigator: Lucas Kühne, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

In this trial will be enclosed iTTP patients treated with caplacizumab from:

• the German real-world cohort of iTTP patients treated with caplacizumab in the years 2018 to 2020 , and
• the respective TITAN and HERCULES trial cohorts.

Description

Inclusion Criteria:

• Confirmed diagnosis of autoimmune thrombotic thrombocytopenic purpura
• Treatment with at least a single dose of caplacizumab, either i.v. or s.c.
• Male or female patients older than 18 years of age

Exclusion Criteria:

• Hereditary thrombotic thrombocytopenic purpura

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
aTTP-Patients; Patients with immune Thrombotic Thrombocytopenic Purpura, who have been treated with caplacizumab (Cablivi®)	Drug: Cablivi; Patients with immune Thrombotic Thrombocytopenic Purpura, who have been treated with caplacizumab (Cablivi®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reliable description and prediction of platelet responses to caplacizumab	Reliable description and prediction of platelet responses to caplacizumab employing mathematic modelling algorithms	Enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk stratification of iTTP patients based on their platelet response to caplacizumab	Description: Predicting the individual thrombocyte response to caplacizumab improves risk stratification of iTTP patients after initiation of caplacizumab therapy. An early risk stratification allows an optimal timing of monitoring intervals during the first weeks after diagnosis, which are often critical	Enrollment
Determination of different clusters of platelet responses to caplacizumab	It will be hypothesized the existence of different clusters of caplacizumab responders during the first weeks of therapy, when ADAMTS13 activity typically is still <10%. A detailed cluster analysis and description of thrombocyte responses to caplacizumab in a large cohort will reliably identify these different responders	Enrollment
Correlation of platelet responses to caplacizumab with patient outcome	It will be hypothesized the existence of different clusters of caplacizumab responders during the first weeks of therapy, when ADAMTS13 activity typically is still <10%. A detailed cluster analysis and description of thrombocyte responses to caplacizumab in a large cohort will reliably identify these different responders	Enrollment

Collaborators and Investigators

• Sponsor: University of Cologne
• Investigators: Principal Investigator: Lucas Kühne, MD, Department II of Internal Medicine, University Hospital of Cologne

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: aTTP; caplacizumab; platelet responses; iTTP
• 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: 2020-11-17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No