A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

Thrombotic Thrombocytopenic Purpura Clinical Trial

Official title:

An Open-label Multicenter Trial to Study the Efficacy and Safety of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04074187
• Other study ID #: EFC16297
• Secondary ID: U1111-1223-4914
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 21, 2019
• Est. completion date: May 19, 2021

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 19, 2021
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

Drug:
• Caplacizumab (ALX-0081)
Pharmaceutical form:Lyophilized powder for solution for injection Route of administration: IV (first dose), SC (all subsequent doses)
• Plasma exchange (PE)
Pharmaceutical form:Plasma (e.g. fresh frozen plasma) Route of administration: Plasma exchange
• Corticosteroid treatment (Methylprednisolone or prednisolone)
Pharmaceutical form:Solution for injection or Tablet Route of administration: IV or Oral
• Immunosuppressive treatment (eg, rituximab)
Pharmaceutical form:Solution for injection (depending on product) Route of administration: IV (depending on product)

Locations

Country	Name	City	State
Japan	Investigational Site Number 3920009	Iruma-Gun
Japan	Investigational Site Number 3920014	Kanazawa-Shi
Japan	Investigational Site Number 3920007	Kashihara-Shi
Japan	Investigational Site Number 3920013	Kawasaki-Shi
Japan	Investigational Site Number 3920001	Kitakyushu-Shi
Japan	Investigational Site Number 3920002	Kumamoto-Shi
Japan	Investigational Site Number 3920003	Kurashiki-Shi
Japan	Investigational Site Number 3920010	Kyoto-Shi
Japan	Investigational Site Number 3920005	Maebashi-Shi
Japan	Investigational Site Number 3920015	Nagoya
Japan	Investigational Site Number 3920011	Osaka-Shi
Japan	Investigational Site Number 3920006	Sendai-Shi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP)	Proportion of participants with a recurrence of aTTP during the overall study period. The success criterion for this study is proportion of evaluable participants (per-protocol population) with a recurrence of aTTP during the overall study period to be 20% or less.	Approximately 2 months up to approximately 6 months
Secondary	Number of recurrences of TTP	Number of recurrences of TTP during study drug treatment (including extensions) and follow-up, as well as during overall study period.	Approximately 2 months up to approximately 6 months
Secondary	Proportion of participants with composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events	Proportion of participants with TTP-related death, a recurrence of TTP, or at least one treatmentemergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions).	Approximately 2 months up to approximately 6 months
Secondary	Time to platelet count response	Time to platelet count response, defined as initial platelet count =150,000/µL with subsequent stop of daily plasma exchange (PE) within 5 days.	Approximately 2 months up to approximately 6 months
Secondary	Proportion of participant who have a platelet count =150,000/µL	Proportion of participant who have a platelet count =150,000/µL on Day 1, 2, 3, 4, 5 and Day 10 and end of study drug treatment (ie, last weekly visit during the overall treatment period).	Approximately 2 months up to approximately 6 months
Secondary	Proportion of participants with refractory TTP	Proportion of participant with refractory TTP, defined as persistent thrombocytopenia, lack of sustained platelet count increment or platelet counts <50,000/µL and persistently elevated LDH (>1.5 x upper limit of normal [ULN]) despite 5 PEs and steroid treatment.	Approximately 2 months up to approximately 6 months
Secondary	Time to normalization of 3 organ damage marker levels	Time to normalization of all 3 of the following organ damage marker levels: Time to LDH = 1 x ULN, and cTnI = 1 x ULN, and serum creatinine = 1 x ULN and time to individual organ damage marker level.	Approximately 2 months up to approximately 6 months
Secondary	Time to stop of daily plasma exchnage (PE)	Time to stop of daily PE	Approximately 2 months up to approximately 6 months
Secondary	Number of days to plasma exchange	The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period	Approximately 2 months up to approximately 6 months
Secondary	Total volume of plasma	The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period	Approximately 2 months up to approximately 6 months
Secondary	Number of days in ICU and in hospital	Number of days in ICU and in hospital in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, in the Follow-up period (of 4 weeks after stop of study drug treatment) and overall study period.	Approximately 2 months up to approximately 6 months
Secondary	Change from baseline in the standardized mini mental state exam (SMMSE) total score	Change from baseline in SMMSE total score on Day 1, (Day 2, 3, 4 as optional) and Day 5 of daily Plasma Exchange (PE) period, and Weeks 1 and 5 of the 30-day postdaily PE period, and the first (7 days after last dosing) and final follow-up (28 days after last dosing) visit.	Approximately 2 months up to approximately 6 months
Secondary	Proportion of participants with at least one treatment emergent thromboembolic event	The treatment-emergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions) will be evaluated.	Approximately 2 months up to approximately 6 months
Secondary	Number of patients with treatment emergent adverse events	Number of Patients with treatment emergent Adverse events (AEs) and serious adverse events (SAEs) and bleeding events	Approximately 2 months up to approximately 6 months
Secondary	Pharmacodynamic (PD) markers	PD parameters: von Willebrand factor antigen(vWF:Ag), coagulation factor VIII clotting activity (FVIII:C), von Willebrand factor ristocetin cofactor activity (vWF:RICO)	Approximately 2 months up to approximately 6 months
Secondary	Pharmacokineticks: plasma concentration	Total caplacizumab plasma concentrations	Approximately 2 months up to approximately 6 months
Secondary	Immunogenicity of caplacizumab	Anti-drug antibodies	Approximately 2 months up to approximately 6 months