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

JRCT ID: jRCT2031230030

Registered date:16/04/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Thrombotic Thrombocytopenic Purpura
• Date of first enrollment: 27/04/2023
• Target sample size: 61
• Countries of recruitment: Austria,Japan,Belgium,Japan,Czechia,Japan,France,Japan,Germany,Japan,Netherlands,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

Primary Outcome

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

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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.

Exclude criteria

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 (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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05468320,2022-001177-31