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

Thrombotic Thrombocytopenic Purpura Clinical Trial

— MAYARI  

Official title:

An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05468320
• Other study ID #: EFC16521
• Secondary ID: U1111-1244-04262
• Status: Recruiting
• Phase: Phase 3
• Start date: November 21, 2022
• Est. completion date: December 13, 2024

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 61
• Est. completion date: December 13, 2024
• Est. primary completion date: December 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

Drug:
• Caplacizumab
Lyophilized powder for solution for injection.
• Corticosteroids
Solution for injection or Tablet

Biological:
• anti-CD20 antibody
Solution for injection

Locations

Country	Name	City	State
Austria	Investigational Site Number : 0400001	Wien
Belgium	Investigational Site Number : 0560001	Leuven
Belgium	Investigational Site Number : 0560003	Yvoir
Canada	Investigational Site Number : 1240004	Halifax	Nova Scotia
Canada	Investigational Site Number : 1240001	Toronto	Ontario
Canada	Investigational Site Number : 1240003	Toronto	Ontario
Czechia	Investigational Site Number : 2030001	Brno
Czechia	Investigational Site Number : 2030002	Hradec Kralove
Czechia	Investigational Site Number : 2030003	Praha 2
France	Investigational Site Number : 2500002	Bois Guillaume
France	Investigational Site Number : 2500005	Lille
France	Investigational Site Number : 2500004	Marseille
France	Investigational Site Number : 2500001	Paris
France	Investigational Site Number : 2500003	Paris
Germany	Investigational Site Number : 2760006	Berlin
Germany	Investigational Site Number : 2760003	Essen
Germany	Investigational Site Number : 2760001	Frankfurt am Main
Germany	Investigational Site Number : 2760004	Hannover
Germany	Investigational Site Number : 2760002	Köln
Germany	Investigational Site Number : 2760007	Leipzig
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number : 3000001	Thessaloniki
Italy	Investigational Site Number : 3800003	Avellino	Campania
Italy	Investigational Site Number : 3800006	Genova
Italy	Investigational Site Number : 3800001	Milano	Lombardia
Italy	Investigational Site Number : 3800005	Verona
Italy	Investigational Site Number : 3800004	Vicenza
Japan	Investigational Site Number : 3920001	Iruma-gun	Saitama
Japan	Investigational Site Number : 3920002	Kashihara-shi	Nara
Japan	Investigational Site Number : 3920003	Kurashiki-shi	Okayama
Netherlands	Investigational Site Number : 5280002	Amersfoort
Netherlands	Investigational Site Number : 5280001	Rotterdam
Spain	Investigational Site Number : 7240004	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Sevilla
Spain	Investigational Site Number : 7240003	Valencia
United Kingdom	Investigational Site Number : 8260002	Liverpool
United Kingdom	Investigational Site Number : 8260001	London	London, City Of
United States	University of Colorado Site Number : 8400012	Aurora	Colorado
United States	Johns Hopkins University Site Number : 8400007	Baltimore	Maryland
United States	University of Alabama Site Number : 8400011	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center Site Number : 8400005	Boston	Massachusetts
United States	Montefiore Medical Center Site Number : 8400019	Bronx	New York
United States	The Ohio State University Comprehensive Cancer Center Site Number : 8400001	Columbus	Ohio
United States	UT Southwestern Medical Center Site Number : 8400002	Dallas	Texas
United States	Duke University Medical Center Site Number : 8400022	Durham	North Carolina
United States	University Of Southern California Site Number : 8400020	Los Angeles	California
United States	Versiti Wisconsion, Inc Site Number : 8400018	Milwaukee	Wisconsin
United States	University of Minnesota Site Number : 8400013	Minneapolis	Minnesota
United States	Tulane University Site Number : 8400021	New Orleans	Louisiana
United States	Perelman Center for Advanced Medicine Site Number : 8400003	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center - Hillman Cancer Ctr Site Number : 8400008	Pittsburgh	Pennsylvania
United States	University of Utah Site Number : 8400009	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).	Remission is defined as sustained Clinical Response (sustained platelet count =150 x 10^9/L and lactate dehydrogenase [LDH] <1.5 x upper limit of normal [ULN] and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits) with either (a) no TPE and no anti- von Willebrand factor (anti-vWF) therapy for = 30 days (Clinical Remission), or (b) with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) = 50% (Complete ADAMTS13 remission), whichever occurs first	Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)
Secondary	Proportion of participants achieving Remission		Overall study period from day 1 to day 168
Secondary	Proportion of participants who require TPE		On-treatment period from day 1 to day 84
Secondary	The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)		Treatment-emergent (TE) period from day 1 to day 112
Secondary	Proportion of participants achieving Clinical Response	Clinical Response is defined as sustained platelet count =150 x 10^9/L and LDH <1.5 x ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.	On-treatment period from day 1 to day 84
Secondary	Proportion of participants achieving Clinical Response		Overall study period from day 1 to day 168
Secondary	Time to platelet count response	Platelet count response defined as time from start of treatment to initial platelet count =150 x 10^9/L that is sustained for =2 days	From day 1 to day 168
Secondary	Proportion of participants refractory to therapy	Refractory to therapy defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts <50 x10^9/L and persistently elevated LDH (>1.5 x ULN) despite 5 days of treatment	On-treatment period from day 1 to day 84
Secondary	Proportion of participants with TTP-related death		On-treatment period from day 1 to day 84
Secondary	Proportion of participants with TTP-related death		Overall study period from day 1 to day 168
Secondary	Proportion of participants with a clinical exacerbation of iTTP	Clinical Exacerbation is defined as after a Clinical Response and before a Clinical Remission, platelet count decreases to <150 x 10^9/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping TPE or anti vWF therapy.	On-treatment period from day 1 to day 84
Secondary	Proportion of participants with a clinical exacerbation of iTTP		Overall study period from day 1 to day 168
Secondary	Proportion of participants with a clinical relapse of iTTP	Clinical Relapse is defined as after a Clinical Remission, platelet count decreases to <150 x 10^9/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A Clinical Relapse must be confirmed by documentation of severe ADAMTS13 deficiency (<10%).	On-treatment period from day 1 to day 84
Secondary	Proportion of participants with a clinical relapse of iTTP		Overall study period from day 1 to day 168