Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura

NCT ID: NCT05468320

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-21
• Study Completion Date: 2024-12-26

Brief Summary

This is a single group, treatment, Phase 3, open-label, single-arm study to evaluate the efficacy and safety of caplacizumab and immunosuppressive therapy (IST) without firstline therapeutic plasma exchange (TPE) with primary endpoint of remission in male and female participants aged 18 to 80 years with immune-mediated thrombotic thrombocytopenic purpura (iTTP).

The anticipated study duration per participant without a recurrence while on therapy is maximum 24 weeks (ie, approximately 1 day for screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up). Participants will have daily assessments during hospitalization and weekly visits for assessments during ongoing treatment with caplacizumab and IST. There will be 3 outpatient visits for assessments during the follow-up period. There will be two additional follow-up visits for participants who do not have ADAMTS13 activity levels of ≥50% at the time of caplacizumab discontinuation.

Detailed Description

The anticipated study duration per participant with the presenting episode therefore is a maximum of about 24 weeks (ie, 1 day of screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up).

Conditions

Thrombotic Thrombocytopenic Purpura

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Caplacizumab & immunosuppressive therapy without 1st-line TPE

All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE

Group Type: EXPERIMENTAL

Caplacizumab

Intervention Type: DRUG

Lyophilized powder for solution for injection.

Corticosteroids

Intervention Type: DRUG

Solution for injection or Tablet

anti-CD20 antibody

Intervention Type: BIOLOGICAL

Solution for injection

Interventions

Caplacizumab

Lyophilized powder for solution for injection.

Intervention Type: DRUG

Corticosteroids

Solution for injection or Tablet

Intervention Type: DRUG

anti-CD20 antibody

Solution for injection

Intervention Type: BIOLOGICAL

Other Intervention Names

Cablivi®; Prednisone® /Prednisolone®; rituximab or biosimilar

Eligibility Criteria

Inclusion Criteria

Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by ADAMTS13 testing within 48 hours (2 days).

Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or 2.

A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a woman of nonchildbearing potential (WONCBP), OR
• Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration.

Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.

Exclusion Criteria

Platelet count ≥100 x 10^9/L. Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30 x 10^9/L (to exclude possible cases of atypical HUS).

Known other causes of thrombocytopenia including but not limited to:

• Clinical evidence of enteric infection with E. coli 0157 or related organism.
• Atypical HUS.
• Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy.
• Known or suspected sepsis.
• Diagnosis of disseminated intravascular coagulation. Congenital TTP (known at the time of study entry). Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia).

Inherited or acquired coagulation disorders. Malignant arterial hypertension. Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.).

Those presenting with severe neurological or cardiac disease. Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy.

Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to:

• vitamin K antagonists.
• direct-acting oral anticoagulants.
• heparin or low molecular weight heparin (LMWH).
• non-steroidal anti-inflammatory molecules other than acetyl salicylic acid. Participants who were previously enrolled in this clinical study (study EFC16521).

Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer.

Positive result on COVID test.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

University of Alabama- Site Number : 8400011

Birmingham, Alabama, United States

Johns Hopkins University- Site Number : 8400007

Baltimore, Maryland, United States

Duke University Medical Center Site Number : 8400022

Durham, North Carolina, United States

The Ohio State University Comprehensive Cancer Center - Site Number : 8400001

Columbus, Ohio, United States

Investigational Site Number : 0560003

Yvoir, , Belgium

Investigational Site Number : 1240001

Toronto, Ontario, Canada

Investigational Site Number : 2030001

Brno, , Czechia

Investigational Site Number : 2030003

Prague, , Czechia

Investigational Site Number : 2500002

Bois-Guillaume, , France

Investigational Site Number : 2500005

Lille, , France

Investigational Site Number : 2500003

Paris, , France

Investigational Site Number : 2500001

Paris, , France

Investigational Site Number : 2760006

Berlin, , Germany

Investigational Site Number : 2760002

Cologne, , Germany

Investigational Site Number : 2760001

Frankfurt am Main, , Germany

Investigational Site Number : 2760004

Hanover, , Germany

Investigational Site Number : 3800003

Avellino, Campania, Italy

Investigational Site Number : 3800001

Milan, Lombardy, Italy

Investigational Site Number : 3800006

Genova, , Italy

Investigational Site Number : 3800005

Verona, , Italy

Investigational Site Number : 3800004

Vicenza, , Italy

Investigational Site Number : 3920003

Kurashiki-shi, Okayama-ken, Japan

Investigational Site Number : 3920001

Iruma-gun, Saitama, Japan

Investigational Site Number : 5280002

Amersfoort, , Netherlands

Investigational Site Number : 7240001

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 8260001

London, London, City of, United Kingdom

Investigational Site Number : 8260002

Liverpool, , United Kingdom

Countries

Austria; Greece; United States; Belgium; Canada; Czechia; France; Germany; Italy; Japan; Netherlands; Spain; United Kingdom

References

Volker LA, Brinkkotter PT. Tailored treatment of acute immune-mediated thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2025 Dec 5;2025(1):614-620. doi: 10.1182/hematology.2025000757.

Reference Type: DERIVED

PMID: 41348038 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25249&tenant=MT_SNY_9011

EFC16521 Plain Language Results Summary

Other Identifiers

U1111-1244-0426

Identifier Type: REGISTRY

Identifier Source: secondary_id

2024-513262-19

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-001177-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC16521

Identifier Type: -

Identifier Source: org_study_id