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

NCT05468320 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: EFC16521U1111-1244-04262024-513262-192022-001177-31
• Study Type: interventional
• Target: 51
• Locations: 11 countries
• Sites: 27

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.

Conditions

Thrombotic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period

  Remission was defined as sustained clinical response with either no TPE and no anti- von Willebrand factor (vWF) therapy for \>=30 days (clinical remission) or with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) activity level \>=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count \>=150 × 10\^9/liter (L) and lactate dehydrogenase (LDH) \<1.5 × upper limit of normal (ULN) and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.

  From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

Secondary Outcomes (13)

• Percentage of Participants Who Achieved Remission During Overall Study Period

  From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

• Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period

  From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)

  From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks)

• Percentage of Participants Who Achieved Clinical Response During On-Treatment Period

  From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks

• Percentage of Participants Who Achieved Clinical Response During Overall Study Period

  From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

Study Arms (1)

Caplacizumab & immunosuppressive therapy without 1st-line TPE

EXPERIMENTAL

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

Drug: Caplacizumab; Drug: Corticosteroids; Biological: anti-CD20 antibody

Interventions

Caplacizumab DRUG

Lyophilized powder for solution for injection.

Also known as: Cablivi®

Caplacizumab & immunosuppressive therapy without 1st-line TPE

Corticosteroids DRUG

Solution for injection or Tablet

Also known as: Prednisone® /Prednisolone®

Caplacizumab & immunosuppressive therapy without 1st-line TPE

anti-CD20 antibody BIOLOGICAL

Solution for injection

Also known as: rituximab or biosimilar

Caplacizumab & immunosuppressive therapy without 1st-line TPE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (27)

University of Alabama- Site Number : 8400011

Birmingham, Alabama, 35233, United States

Location

Johns Hopkins University- Site Number : 8400007

Baltimore, Maryland, 21287, United States

Location

Duke University Medical Center Site Number : 8400022

Durham, North Carolina, 27710-4000, United States

Location

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

Columbus, Ohio, 43210, United States

Location

Investigational Site Number : 0560003

Yvoir, 5530, Belgium

Location

Investigational Site Number : 1240001

Toronto, Ontario, M5B 1W8, Canada

Location

Investigational Site Number : 2030001

Brno, 62500, Czechia

Location

Investigational Site Number : 2030003

Prague, 128 00, Czechia

Location

Investigational Site Number : 2500002

Bois-Guillaume, 76230, France

Location

Investigational Site Number : 2500005

Lille, 59037, France

Location

Investigational Site Number : 2500003

Paris, 75010, France

Location

Investigational Site Number : 2500001

Paris, 75012, France

Location

Investigational Site Number : 2760006

Berlin, 10117, Germany

Location

Investigational Site Number : 2760002

Cologne, 50937, Germany

Location

Investigational Site Number : 2760001

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number : 2760004

Hanover, 30625, Germany

Location

Investigational Site Number : 3800003

Avellino, Campania, 83100, Italy

Location

Investigational Site Number : 3800001

Milan, Lombardy, 20122, Italy

Location

Investigational Site Number : 3800006

Genova, 16132, Italy

Location

Investigational Site Number : 3800005

Verona, 37134, Italy

Location

Investigational Site Number : 3800004

Vicenza, 36100, Italy

Location

Investigational Site Number : 3920003

Kurashiki-shi, Okayama-ken, 710-8602, Japan

Location

Investigational Site Number : 3920001

Iruma-gun, Saitama, 350-0495, Japan

Location

Investigational Site Number : 5280002

Amersfoort, 3818 TZ, Netherlands

Location

Investigational Site Number : 7240001

Madrid / Madrid, Madrid, Comunidad de, 28007, Spain

Location

Investigational Site Number : 8260001

London, London, City of, NW1 2PG, United Kingdom

Location

Investigational Site Number : 8260002

Liverpool, L7 8XP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41348038 DERIVED

Related Links

• EFC16521 Plain Language Results Summary

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

caplacizumab; Adrenal Cortex Hormones; Prednisone; Prednisolone; Rituximab; Biosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 21, 2022
• Study Start: November 21, 2022
• Primary Completion: December 26, 2024
• Study Completion: December 26, 2024
• Last Updated: December 30, 2025
• Results First Posted: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

NL (1); CA (1); CZ (2); BE (1); ES (1); US (4); FR (4); IT (5); GB (2); JP (2); DE (4)