Efficacy and Safety Evaluation of BAY 3018250 in Symptomatic Proximal Deep Vein Thrombosis: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial

The primary objectives of this study are to quantify the effect of **BAY 3018250** on clot lysis in patients with symptomatic proximal deep vein thrombosis (**DVT**) and to assess the safety of BAY 3018250 in these patients. Evaluating the efficacy of BAY 3018250 in promoting thrombolysis is clinically relevant as it may offer a therapeutic option for managing proximal DVT, a condition associated with significant morbidity and risk of complications such as pulmonary embolism.

The secondary objective is to quantify the effect of BAY 3018250 on clot lysis in patients with proximal DVT based on additional endpoints. This further analysis aims to provide a comprehensive understanding of the therapeutic potential and safety profile of BAY 3018250 in the context of thrombolytic therapy.

The clinical trial involves a total of **3 participants** diagnosed with **proximal deep vein thrombosis (DVT)**. The study population includes both male and female subjects, provided the females are postmenopausal or have undergone a hysterectomy. Participants are aged 18 years or older, with a body weight ranging from 50 to 130 kg. The trial population was selected based on the presence of acute symptomatic proximal DVT, confirmed by compression ultrasound, with symptoms persisting for 14 days or less. The DVT must involve at least one of the proximal veins, such as the popliteal, femoral, common femoral, or external iliac vein, with adequate visualization of the thrombus's most proximal end. Participants are required to be on therapeutic dose anticoagulation with low molecular weight heparins (LMWHs) and/or direct oral anticoagulants (DOACs) as per product labels. The study does not include a vulnerable population, and all participants have provided signed informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of BAY 3018250 in patients with symptomatic proximal deep vein thrombosis (DVT). The trial will involve multiple centers and is expected to last until October 2025, with recruitment starting in November 2023. Participants will be randomly assigned to receive either BAY 3018250 or a placebo, with the primary objective being to quantify the effect of BAY 3018250 on clot lysis and assess its safety profile. The trial will include a series of study visits, beginning with an inclusion visit where eligibility criteria are confirmed, including age, documented acute symptomatic proximal DVT, and body weight requirements. Participants must provide signed informed consent to be included in the study.

Following the inclusion visit, participants will undergo a series of follow-up visits at 6 hours, 24 hours, Day 7, Day 30, and Day 90 to assess primary and secondary endpoints. These endpoints include the area under the curve of the ratio to baseline of clot burden, the number of bleeding events, changes in leg pain severity, and functional status post-venous thromboembolism. The end-of-study visit will occur on Day 90, marking the completion of the participant's involvement in the trial. The expected length of participant involvement is approximately 90 days, with conditions for early termination including withdrawal of consent or adverse events that compromise participant safety.

The trial will utilize a **concentrate for solution for infusion** form of BAY 3018250, with administration routes specified as subcutaneous and other use. The placebo will be a solution matching the BAY 3018250 solution. The study is not classified as low intervention and is categorized as a Phase 4 trial. Participants will be monitored closely throughout the trial to ensure adherence to the protocol and to manage any potential adverse effects. The trial's design and procedures are structured to provide robust data on the therapeutic potential of BAY 3018250 in the treatment of proximal DVT.

The clinical trial involves the administration of **BAY 3018250**, an experimental medication, which is a **concentrate for solution for infusion**. The active substance, BAY 3018250, is a protein of other origin, developed by Bayer AG. The pharmaceutical form is designed for infusion, and the route of administration is categorized as "other use." The trial does not specify a maximum daily dose or total dose amount, and the treatment period can extend up to 1111 days. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental medication, a **placebo solution** is used as a comparator treatment. This placebo is specifically formulated to match the BAY 3018250 solution in appearance and administration method, ensuring the study remains double-blind. The placebo does not contain any active substances and serves to assess the efficacy and safety of BAY 3018250 by providing a control group for comparison.

Furthermore, the study includes the use of **low molecular weight heparin**, classified under the **heparin group** with the ATC code B01AB. This medication is administered subcutaneously, with a maximum daily dose of 2 mg/kg and a total dose limit of 60 mg/kg over a treatment period of up to 30 days. Low molecular weight heparin is a biological product and serves as an auxiliary treatment in the trial, providing standard-of-care therapy for patients with symptomatic proximal deep vein thrombosis. Compliance with the administration schedule will be closely monitored to ensure accurate assessment of the trial outcomes.

The efficacy of BAY 3018250 in patients with symptomatic proximal deep vein thrombosis (DVT) will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the **area under the curve (AUCn)** from 6 hours to 30 days of the ratio to baseline of clot burden, as evaluated by repeated quantitative ultrasound at specified timepoints: 6 hours, 24 hours, Day 7, and Day 30. Additionally, the number of participants experiencing a composite of major and clinically relevant non-major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH), will be recorded up to Day 15.

Secondary efficacy endpoints include the ratio to baseline of clot burden assessed at 6 hours, 24 hours, Day 7, Day 30, and Day 90. Changes from baseline in leg pain severity will be measured using the Likert pain scale at the same timepoints. Furthermore, changes in post-venous thromboembolism functional status (PVFS) will be evaluated at Day 7, Day 30, and Day 90. The incidence of recurrent venous thromboembolism (VTE) will also be monitored up to Day 90. These assessments will provide a comprehensive evaluation of the therapeutic impact of BAY 3018250 on clot lysis and patient outcomes in the context of proximal DVT.