Clinical trial NCT06357572: Real-life Clinical FEIBA Samples Measured Using the Version A of the HemA EnzySystem
Official title: Real-life Clinical FEIBA Samples Measured Using the Version A of the HemA EnzySystem
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A With Inhibitor
Hemophilia A
Lead sponsor: Enzyre B.V.
Sponsor class: INDUSTRY
Collaborators: name: Instytut Hematologii i Transfuzjologii, Warschau, Poland
First posted: 2024-04-10
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hemophilia A patients at the Institute of Hematology and Transfusion Medicine who are on prophylactic or on-demand FEIBA treatment.

Brief summary: The goal of this observational study is to assess if the version A of the HemA EnzySystem, a novel portable coagulation testing platform, can be used in patients with hemophilia A treated with Factor VIII Bypassing Agent (FEIBA). The main question\[s\] it aims to answer are:

* Can the version A of the HemA EnzySystem can record thrombin generation within a time frame of 60 min in fresh whole blood samples of patients with hemophilia A treated with FEIBA?
* Are the TGA results of the version A of the HemA EnzySystem in agreement with the TGA results obtained with conventional methods in fresh non frozen plasma?

Participants are asked to fill in a questionnaire regarding their general health and hemophilia treatment. Subsequently, blood will be drawn from the patients before, and at 30, 120, and 240 minutes after FEIBA administration. Whole blood is immediately tested using the Version A HemA EnzySystem, and plasma is generated for testing with the Ceveron s100 (Technoclone). Leftover samples are frozen for later additional coagulation testing.

Detailed description: Rationale: Hemophilia is an X-linked hemostatic bleeding disorder characterized by a lack of coagulation factor VIII activity (HemA) or factor IX activity (HemB). Spontaneous major bleeding in joints and muscles frequently occur when factor activity levels are low. Currently, there is a growing evidence that the bleeding phenotype of hemophilia A patients is not only reflected by the actual factor VIII activity level, as there is a large variety in bleeding among patients with similar factor VIII activity.

Currently, patients with severe Hemophilia A are treated with either FVIII containing products or Emicizumab. Initially emicizumab was described for patients who developed inhibitors as inhibitors do not interfere with emicizumab. Despite, bleeding complications still may occur and therefore bypassing therapies are still of great importance. Unfortunately, monitoring treatment with these drugs is a challenge.

Thrombin generation profile may be an additional tool in hemophilia patients to differentiate between bleeding phenotype, to guide prophylactic replacement therapy and adjust bypassing therapy, especially in patients treated with emicizumab. Based on recent studies, thrombin generation as a global hemostasis assay offers an opportunity to assess the hemostatic capacity of patients, and therefore has much potential for monitoring therapy. To facilitate this, a hand-held in vitro diagnostic medical device able to simultaneously measure multiple disease biomarkers with a single drop of blood is currently in development, focusing on simultaneous measurements of Factor VIII activity and Thrombin generation.

Objective: The primary objective of this study is to demonstrate that the version A of the HemA EnzySystem can record thrombin generation within a time frame of 60 min in fresh whole blood samples of patients with hemophilia A treated with Factor VIII Bypassing Agent (FEIBA). As secondary objective, the study results will be validated with a Thrombin Generation Assay (TGA) measured in freshly obtained non frozen plasma.

Study design: This is a cross-sectional observational study. All participants are asked to fill a questionnaire prior to blood collection of four tubes. Blood sample measurements will be conducted within a two-hour time frame using the version A of the HemA EnzySystem and the preparation of plasma using a standard TGA assay. Any remaining blood material will be processed and stored.

Study population: The study population consists of 6 patients treated with FEIBA. In total, at least 24 samples are tested, four for each patient (t=0, 30, 120 and 240 minutes).

Eligibility criteria: Inclusion criteria (all of the following)

* Diagnosed with mild (FVIII activity levels 5-40%), moderate (FVIII activity levels 1-5%) or severe hemophilia A (FVIII activity levels \<1%)
* With inhibitors
* On prophylactic or on-demand treatment with FEIBA (variation in dosing and duration of therapy use)

Exclusion Criteria:

* use of anticoagulants or platelet antagonists (aspirin or any TAR);
* known allergy to stainless steel;
* a bleeding episode within the last two weeks;
* clinical indication of liver cirrhosis (ultrasonography indication, enlarged spleen, decreased platelet count \<100 G/l);
* Signs of inflammation or infection
* Current use of:

NSAIDs; antimicrobial medication; thyroid inhibitors or SSRI's;

Primary outcomes:
measure: Time between venipuncture and TGA result
timeFrame: 2 hours
Secondary outcomes:
measure: Agreement between TGA obtained with the EnzySystem HemA version A and conventional TGA results
timeFrame: 6 hours
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Institute of Hematology and Blood Transfusion
state: Mazowieckie Województwo
Study officials:
References: