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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

Caplacizumab and immunosuppressive therapy without firstline therapeutic plasma exchange in adults with immune-mediated thrombotic thrombocytopenic purpura
(MAYARI)

56

The median (First Quartile; Third Quartile) age of the modified intent-to-treat (mITT) population was 46.0 years (36.0; 55.0), and 32 (69.6%) participants were females. Seventeen (37.0%) participants were White, 8 (17.4%) were Black or African American, and 6 (13.0%) were Asian.

- Enrolled and exposed: 50 - Completed the study intervention period as per protocol: 43 - Completed the study as per protocol: 49 - mITT population: 46 - Safety population: 50

- A total of 46 (92.0%) participants experienced at least 1 treatment-emergent adverse event (TEAE), with the highest percentage of participants experiencing an event in the Nervous system disorders system organ class (SOC). - The majority of treatment-emergent SAEs were considered to be not related to the study intervention as per the Investigator. - There were no deaths reported during the study.

Primary endpoint: In total, 43 of the 46 participants (93.5%) were responders and achieved remission without requiring TPE (95% confidence interval [CI]: 82.5% to 97.8%). Secondary endpoints: In the mITT population: - Irrespective of requiring TPE, 44 of the 46 (95.7%) participantsachieved remission (95% CI: 85.5% to 98.8%). - Overall, 2 of the 46 (4.3%) participants (95% CI: 1.2% to 14.5%)required plasma exchange on Days 15 and 17, respectively, aftercaplacizumab initiation. - Clinical response was achieved in 45 of the 46 (97.8%) ofparticipants (95% CI: 88.7% to 99.6%). - A total of 25 of the 46 (54.3%) participants experienced a rapidplatelet count response within a median of 4 days (95% CI: 3 to 5days) after the initial caplacizumab dose. - Recurrence of iTTP (ie, exacerbation or relapse) was notobserved in any of the participants in the mITT population. - There was no iTTP-related death amongst the participants whoreceived caplacizumab.

A total of 50 participants were enrolled in and exposed to this study.The study demonstrated that caplacizumab andimmunosuppressive therapy, without first-line TPE, achievedclinical efficacy in more than 90% of participants with acute iTTPand exhibited a favorable safety profile.

Yes

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

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230030

Obara Kentaro

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Complete

April. 27, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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.

Participants are excluded from the study if any of the following criteria apply:
- Platelet count >=100 x 10^9/L.
- Serum creatinine level >2.26 mg/dL (200 micro mol/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.

Both

Thrombotic Thrombocytopenic Purpura

Drug: Caplacizumab
Lyophilized powder for solution for injection.
Drug: Corticosteroids
Solution for injection or Tablet
Biological: anti-CD20 antibody
Solution for injection, Other Name: rituximab or biosimilar

1. Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).
[Time Frame baseline: Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up) ]
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

1. Proportion of participants achieving Remission
[Time Frame baseline:Overall study period ]
2. Proportion of participants who require TPE
[Time Frame baseline:On-treatment period from day 1 to day 84]
3. The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
[Time Frame baseline:Treatment-emergent (TE) period from day 1 to day 112]
4. Proportion of participants achieving Clinical Response
[Time Frame baseline:On-treatment period from day 1 to day 84]
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.
5. Proportion of participants achieving Clinical Response
[Time Frame baseline:Overall study period from day 1 to day 168]
6. Time to platelet count response
[Time Frame baseline:From day 1 to day 168]
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
7. Proportion of participants refractory to therapy
[Time Frame baseline:On-treatment period from day 1 to day 84]
Refractory to therapy defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts <50 x 10^9/L and persistently elevated LDH (>1.5 x ULN) despite 5 days of treatment
8. Proportion of participants with TTP-related death
[Time Frame baseline:On-treatment period from day 1 to day 84]
9. Proportion of participants with TTP-related death
[Time Frame baseline:Overall study period from day 1 to day 168]
10. Proportion of participants with a clinical exacerbation of iTTP
[Time Frame baseline:On-treatment period from day 1 to day 84]
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.
11. Proportion of participants with a clinical exacerbation of iTTP
[Time Frame baseline:Overall study period from day 1 to day 168]
12. Proportion of participants with a clinical relapse of iTTP
[Time Frame baseline:On-treatment period from day 1 to day 84]
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%).
13. Proportion of participants with a clinical relapse of iTTP
[Time Frame baseline:Overall study period from day 1 to day 168

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Mar. 28, 2023

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