Clinical trial NCT04074187: A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Official title: An Open-label Multicenter Trial to Study the Efficacy and Safety of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Thrombotic Thrombocytopenic Purpura
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-08-29
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the effect of caplacizumab on prevention of recurrence of aTTP (proportion of participants with a recurrence of aTTP) during the overall study period.

Secondary Objectives:

* To evaluate effect of caplacizumab on

  * prevention of recurrence of TTP (the number of recurrences of TTP) during overall study period.
  * a composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events during study drug treatment
  * restoring platelet counts as a measure of prevention of further microvascular thrombosis
  * refractory disease
  * biomarkers of organ damage: LDH, cardiac troponin I, serum creatinine
  * plasma exchange (PE) parameters (days of PE and volume of plasma used), days in intensive care unit, days in hospital
  * cognitive status of Japanese patients
* To evaluate safety profile of caplacizumab in Japanese patients
* To evaluate effect of caplacizumab on pharmacodynamic (PD) markers in Japanese patients
* To evaluate pharmacokinetic (PK) profile of caplacizumab in Japanese patients
* To evaluate immunogenicity of caplacizumab in Japanese patients

Detailed description: Study duration per participant is approximately 2 months up to approximately 6 months in case of treatment extension and recurrence during the study drug treatment period.

Eligibility criteria: Inclusion criteria :

* Japanese participant must be 18 years or older at the time of signing the informed consent.
* Participants who have a clinical diagnosis of aTTP (initial or recurrent), which includes thrombocytopenia (defined as platelet count \<100,000/µL), microangiopathic hemolytic anemia as evidenced by red blood cell fragmentation (eg, presence of schistocytes), and increased levels of LDH
* Participants who require initiation of daily PE treatment and have received a maximum of 1 PE treatment prior to enrollment in the study
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
* Capable of giving signed informed consent

Exclusion criteria:

* Platelet count ≥100,000/µL,
* Serum creatinine level \> 2.3mg/dL in case platelet count is \> 30,000µL
* Known other causes of thrombocytopenia
* Congenital TTP
* Clinically significant active bleeding or high risk of bleeding
* Malignant arterial hypertension
* Known chronic treatment with anticoagulant treatment that cannot be stopped
* Participants who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
* Participants currently or less than 28 days prior to enrollment in this study, enrolled in a clinical study with another investigational drug or device
* Clinical condition other than that associated with TTP, with life expectancy \< 6 months, such as end-stage malignancy
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
* Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures

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

Primary outcomes:
measure: Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP)
timeFrame: Approximately 2 months up to approximately 6 months
Secondary outcomes:
measure: Number of recurrences of TTP
timeFrame: Approximately 2 months up to approximately 6 months
measure: Proportion of participants with composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events
timeFrame: Approximately 2 months up to approximately 6 months
measure: Time to platelet count response
timeFrame: Approximately 2 months up to approximately 6 months
measure: Proportion of participant who have a platelet count ≥150,000/μL
timeFrame: Approximately 2 months up to approximately 6 months
measure: Proportion of participants with refractory TTP
timeFrame: Approximately 2 months up to approximately 6 months
measure: Time to normalization of 3 organ damage marker levels
timeFrame: Approximately 2 months up to approximately 6 months
measure: Time to stop of daily plasma exchnage (PE)
timeFrame: Approximately 2 months up to approximately 6 months
measure: Number of days to plasma exchange
timeFrame: Approximately 2 months up to approximately 6 months
measure: Total volume of plasma
timeFrame: Approximately 2 months up to approximately 6 months
measure: Number of days in ICU and in hospital
timeFrame: Approximately 2 months up to approximately 6 months
measure: Change from baseline in the standardized mini mental state exam (SMMSE) total score
timeFrame: Approximately 2 months up to approximately 6 months
measure: Proportion of participants with at least one treatment emergent thromboembolic event
timeFrame: Approximately 2 months up to approximately 6 months
measure: Number of patients with treatment emergent adverse events
timeFrame: Approximately 2 months up to approximately 6 months
measure: Pharmacodynamic (PD) markers
timeFrame: Approximately 2 months up to approximately 6 months
measure: Pharmacokineticks: plasma concentration
timeFrame: Approximately 2 months up to approximately 6 months
measure: Immunogenicity of caplacizumab
timeFrame: Approximately 2 months up to approximately 6 months
Other outcomes:
Locations:
city: Iruma-Gun
country: Japan
facility: Investigational Site Number 3920009
city: Kanazawa-Shi
country: Japan
facility: Investigational Site Number 3920014
city: Kashihara-Shi
country: Japan
facility: Investigational Site Number 3920007
city: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 3920013
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Kurashiki-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 3920010
city: Maebashi-Shi
country: Japan
facility: Investigational Site Number 3920005
city: Nagoya
country: Japan
facility: Investigational Site Number 3920015
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 3920011
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 3920006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Miyakawa Y, Imada K, Ichikawa S, Uchiyama H, Ueda Y, Yonezawa A, Fujitani S, Ogawa Y, Matsushita T, Asakura H, Nishio K, Suzuki K, Hashimoto Y, Murakami H, Tahara S, Tanaka T, Matsumoto M. The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study. Int J Hematol. 2023 Mar;117(3):366-377. doi: 10.1007/s12185-022-03495-6. Epub 2022 Nov 24.