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

Primary Purpose

Thrombotic Thrombocytopenic Purpura

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Caplacizumab
Corticosteroids
anti-CD20 antibody
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 1e+9/L. Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30 x 1e+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 (ie, coma, seizures) or severe cardiac disease (cTnl >2.5 x ULN).

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 the Screening SARS-CoV-2 RT-PCR test.

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

Sites / Locations

  • University of Alabama-Site Number:8400011Recruiting
  • Johns Hopkins University-Site Number:8400007Recruiting
  • Beth Israel Deaconess Medical Center-Site Number:8400005Recruiting
  • Montefiore Medical Center-Site Number:8400019Recruiting
  • The Ohio State University Comprehensive Cancer Center-Site Number:8400001Recruiting
  • University of Utah-Site Number:8400009Recruiting
  • Investigational Site Number :0400001Recruiting
  • Investigational Site Number :0560001Recruiting
  • Investigational Site Number :0560003Recruiting
  • Investigational Site Number :2500002Recruiting
  • Investigational Site Number :2500005Recruiting
  • Investigational Site Number :2500004Recruiting
  • Investigational Site Number :2500003Recruiting
  • Investigational Site Number :2500001Recruiting
  • Investigational Site Number :2760006Recruiting
  • Investigational Site Number :2760003Recruiting
  • Investigational Site Number :2760001Recruiting
  • Investigational Site Number :2760004Recruiting
  • Investigational Site Number :2760002Recruiting
  • Investigational Site Number :3000001Recruiting
  • Investigational Site Number :3800003Recruiting
  • Investigational Site Number :3800001Recruiting
  • Investigational Site Number :3800005Recruiting
  • Investigational Site Number :3920001Recruiting
  • Investigational Site Number :5280002Recruiting
  • Investigational Site Number :5280001Recruiting
  • Investigational Site Number :7240004Recruiting
  • Investigational Site Number :7240001Recruiting
  • Investigational Site Number :7240002Recruiting
  • Investigational Site Number :7240003Recruiting
  • Investigational Site Number :8260001Recruiting
  • Investigational Site Number :8260002Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Caplacizumab & immunosuppressive therapy without 1st-line TPE

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of participants achieving Remission
Proportion of participants who require TPE
The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
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.
Proportion of participants achieving Clinical Response
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
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
Proportion of participants with TTP-related death
Proportion of participants with TTP-related death
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.
Proportion of participants with a clinical exacerbation of iTTP
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%).
Proportion of participants with a clinical relapse of iTTP

Full Information

First Posted
July 18, 2022
Last Updated
August 24, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05468320
Brief Title
Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 24, 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 21, 2022 (Actual)
Primary Completion Date
December 13, 2024 (Anticipated)
Study Completion Date
December 13, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Caplacizumab & immunosuppressive therapy without 1st-line TPE
Arm Type
Experimental
Arm Description
All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody [rituximab or biosimilar]) without first line TPE
Intervention Type
Drug
Intervention Name(s)
Caplacizumab
Other Intervention Name(s)
Cablivi®
Intervention Description
Lyophilized powder for solution for injection.
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Other Intervention Name(s)
Prednisone® /Prednisolone®
Intervention Description
Solution for injection or Tablet
Intervention Type
Biological
Intervention Name(s)
anti-CD20 antibody
Other Intervention Name(s)
rituximab or biosimilar
Intervention Description
Solution for injection
Primary Outcome Measure Information:
Title
Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).
Description
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
Time Frame
Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)
Secondary Outcome Measure Information:
Title
Proportion of participants achieving Remission
Time Frame
Overall study period from day 1 to day 168
Title
Proportion of participants who require TPE
Time Frame
On-treatment period from day 1 to day 84
Title
The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Time Frame
Treatment-emergent (TE) period from day 1 to day 112
Title
Proportion of participants achieving Clinical Response
Description
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.
Time Frame
On-treatment period from day 1 to day 84
Title
Proportion of participants achieving Clinical Response
Time Frame
Overall study period from day 1 to day 168
Title
Time to platelet count response
Description
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
Time Frame
From day 1 to day 168
Title
Proportion of participants refractory to therapy
Description
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
Time Frame
On-treatment period from day 1 to day 84
Title
Proportion of participants with TTP-related death
Time Frame
On-treatment period from day 1 to day 84
Title
Proportion of participants with TTP-related death
Time Frame
Overall study period from day 1 to day 168
Title
Proportion of participants with a clinical exacerbation of iTTP
Description
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.
Time Frame
On-treatment period from day 1 to day 84
Title
Proportion of participants with a clinical exacerbation of iTTP
Time Frame
Overall study period from day 1 to day 168
Title
Proportion of participants with a clinical relapse of iTTP
Description
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%).
Time Frame
On-treatment period from day 1 to day 84
Title
Proportion of participants with a clinical relapse of iTTP
Time Frame
Overall study period from day 1 to day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
contact-us@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama-Site Number:8400011
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Name
Johns Hopkins University-Site Number:8400007
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Name
Beth Israel Deaconess Medical Center-Site Number:8400005
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Montefiore Medical Center-Site Number:8400019
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Individual Site Status
Recruiting
Facility Name
The Ohio State University Comprehensive Cancer Center-Site Number:8400001
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Utah-Site Number:8400009
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0400001
City
Wien
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0560001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0560003
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2500002
City
Bois Guillaume
ZIP/Postal Code
76230
Country
France
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2500005
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2500004
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2500003
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2500001
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2760006
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2760003
City
Essen
ZIP/Postal Code
45122
Country
Germany
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2760001
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2760004
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :2760002
City
Koln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3000001
City
Thessaloniki
ZIP/Postal Code
57010
Country
Greece
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3800003
City
Avellino
State/Province
Campania
ZIP/Postal Code
83100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3800001
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3800005
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3920001
City
Iruma-gun
State/Province
Saitama
ZIP/Postal Code
350-0495
Country
Japan
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :5280002
City
Amersfoort
ZIP/Postal Code
3818 TZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :5280001
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240004
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240001
City
Madrid / Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240002
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :7240003
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260001
City
London
State/Province
London, City Of
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260002
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Learn more about this trial

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

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