Clinical trial NCT05468320: Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thrombotic Thrombocytopenic Purpura
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-07-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).
timeFrame: Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)
Secondary outcomes:
measure: Proportion of participants achieving Remission
timeFrame: Overall study period from day 1 to day 168
measure: Proportion of participants who require TPE
timeFrame: On-treatment period from day 1 to day 84
measure: The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
timeFrame: Treatment-emergent (TE) period from day 1 to day 112
measure: Proportion of participants achieving Clinical Response
timeFrame: On-treatment period from day 1 to day 84
measure: Proportion of participants achieving Clinical Response
timeFrame: Overall study period from day 1 to day 168
measure: Time to platelet count response
timeFrame: From day 1 to day 168
measure: Proportion of participants refractory to therapy
timeFrame: On-treatment period from day 1 to day 84
measure: Proportion of participants with TTP-related death
timeFrame: On-treatment period from day 1 to day 84
measure: Proportion of participants with TTP-related death
timeFrame: Overall study period from day 1 to day 168
measure: Proportion of participants with a clinical exacerbation of iTTP
timeFrame: On-treatment period from day 1 to day 84
measure: Proportion of participants with a clinical exacerbation of iTTP
timeFrame: Overall study period from day 1 to day 168
measure: Proportion of participants with a clinical relapse of iTTP
timeFrame: On-treatment period from day 1 to day 84
measure: Proportion of participants with a clinical relapse of iTTP
timeFrame: Overall study period from day 1 to day 168
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama- Site Number : 8400011
state: Alabama
city: Baltimore
country: United States
facility: Johns Hopkins University- Site Number : 8400007
state: Maryland
city: Durham
country: United States
facility: Duke University Medical Center Site Number : 8400022
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center - Site Number : 8400001
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah- Site Number : 8400009
state: Utah
city: Wien
country: Austria
facility: Investigational Site Number : 0400001
city: Yvoir
country: Belgium
facility: Investigational Site Number : 0560003
city: Toronto
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Brno
country: Czechia
facility: Investigational Site Number : 2030001
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number : 2030002
city: Praha 2
country: Czechia
facility: Investigational Site Number : 2030003
city: Bois Guillaume
country: France
facility: Investigational Site Number : 2500002
city: Lille
country: France
facility: Investigational Site Number : 2500005
city: Paris
country: France
facility: Investigational Site Number : 2500003
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760006
city: Essen
country: Germany
facility: Investigational Site Number : 2760003
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number : 2760001
city: Hannover
country: Germany
facility: Investigational Site Number : 2760004
city: Köln
country: Germany
facility: Investigational Site Number : 2760002
city: Leipzig
country: Germany
facility: Investigational Site Number : 2760007
city: Avellino
country: Italy
facility: Investigational Site Number : 3800003
state: Campania
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Genova
country: Italy
facility: Investigational Site Number : 3800006
city: Verona
country: Italy
facility: Investigational Site Number : 3800005
city: Vicenza
country: Italy
facility: Investigational Site Number : 3800004
city: Kurashiki-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Okayama
city: Iruma-gun
country: Japan
facility: Investigational Site Number : 3920001
state: Saitama
city: Amersfoort
country: Netherlands
facility: Investigational Site Number : 5280002
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240001
state: Madrid, Comunidad De
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
city: Liverpool
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: