A Study to Learn About How Safe BAY 3389934 is, Its Suitable Dose, and How it Affects the Participants With Sepsis Induced Coagulopathy

Official title

First in Patient, Dose Escalation, Open Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Infusion of BAY 3389934 to Patients With Sepsis Induced Coagulopathy

Overview

Researchers are looking for a better way to treat people who have sepsis induced coagulopathy. Sepsis happens when bacteria and their toxins spread in the blood, causing an infection. To overcome the infection the body responds activating the immune system, sometimes this immune response is too active and causes uncontrolled blood clot formation, also called sepsis-induced coagulopathy. Sepsis coagulopathy damages blood vessels and organs and leads to low platelet levels in the body. In severe cases, it can even lead to death. The main purpose of this first in patient study is to learn about how safe BAY 3389934 is, its suitable dose, and how it affects the participants with sepsis induced coagulopathy. For this study, researchers will enroll people receiving treatment for sepsis induced coagulopathy in a hospital intensive care unit (ICU). For this, the researchers will collect the number of participants with medical problems during and after receiving BAY 3389934. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatments. Participants will be divided into 2 groups. The first group will receive the lowest starting dose of BAY3389934. The researcher will carefully monitor how the participant responds to the medication and may adjust the dose, either increasing or decreasing it based on the safety and the tolerability of the drug. If no serious side effects are reported from the first group, the second group will receive higher dose of BAY3389934. Each participant will be in the study for around 28 days. During the study, the doctors and their study team will: * Take blood and urine samples, * Do physical examinations, * Check vital signs such as body temperature, blood pressure and heart rate, * Examine heart health using electrocardiogram (ECG)

Interventions

• Drug BAY3389934
  Solution for IV infusion

Primary outcome measures

• The number of participants with TEAEs (treatment-emergent adverse events) [Time frame: After the first administration of study intervention to 1 hour after stop from study intervention, up to 97 hours]
• Severity of TEAEs [Time frame: After the first administration of study intervention to 1 hour after stop from study intervention, up to 97 hours]

Secondary outcome measures (2)

• Activated partial thromboplastin time (aPTT) [Time frame: From the first administration of study intervention day 1 to day 6]
• Prothrombin time (PT) [Time frame: From the first administration of study intervention day 1 to day 6]

Eligibility criteria

Inclusion criteria

• Participant must be ≥ 18 and ≤ 80 years of age at the time of signing the informed consent.
• Participants with diagnosed sepsis according to sepsis-3 criteria. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
• participants with suspected or documented origin of infection.
• Participants with coagulopathy defined by at least one of the following within 24 hours prior start of study intervention: INR ≥1.40, platelet count in the range of ≥ 30,000/mm3 to < 150,000/mm3 OR greater than 30% decrease in platelets in 24 hours without other known etiology. The platelet count after decrease should not be < 30,000/mm3.
• Participants must be receiving treatment in an ICU.
• Informed consent of capable participant or, in case of participant being incapable of giving informed consent, consent for study inclusion will be sought according to applicable laws and regulations.

Exclusion criteria

• Clinically significant active bleeding; known bleeding disorder, history of major traumatic or non-traumatic bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months.
• Low platelets level or abnormal coagulation status due to any other reason than sepsis.
• Participants with indication for therapeutic dose of: anticoagulation (heparin, argatroban, vitamin K antagonists/warfarin, dabigatran, apixaban, rivaroxaban, edoxaban), oral antiplatelet agents (clopidogrel, ticagrelor, ticlopidine, prasugrel) except low dose (≤100mg) acetyl salicylic acid (ASA), digoxin, metformin
• Any active malignancy
• Pregnancy or breastfeeding.
• Chronic liver disease Child-Pugh Class C.
• Participants experienced major surgery or major trauma (intrathoracic, intra-abdominal, pelvic or femur) or surgery/trauma in any other area with potentially clinically significant consequences due to bleeding within 28 days before study drug administration.
• Participants experienced neurotrauma or neurosurgery (brain, spine) or orthopedic surgery in spine within 6 months before study drug administration

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Basic science

Study locations

France · 7 centers

• CHRU de Tours - Hôpital Bretonneau - Médecine Intensive Réanimation — Tours
• Hopitaux Universitaires de Strasbourg Nouvel Hopital Civil - Service de Médecine Intensive — Strasbourg
• Centre Hospitalier Universitaire de Limoges Dupuytren 1 - Service de réanimation polyvalen — Limoges
• Centre Hospitalier Universitaire d'Angers - Médecine Intensive Réanimation et Médecine Hyp — Angers
• Centre Hospitalier Départemental Vendée - Service de réanimation polyvalente — La Roche-sur-Yon
• Hopital Hotel Dieu Nantes - Service de Médecine Intensive Réanimation — Nantes
• Hôpital Raymond-Poincaré - Service de Médecine Intensive - Réanimation, Médecine Hyperbare — Garches

Netherlands · 5 centers

• Universitair Medisch Centrum St. Radboud - Intensive Care — Nijmegen
• Canisius WIlhelmina Ziekenhuis - Intensive Care — Nijmegen
• Jeroen Bosch Ziekenhuis - Intensive Care — 's-Hertogenbosch
• Medisch Spectrum Twente - Intensive Care — Enschede
• Erasmus Medisch Centrum - Intensive Care — Rotterdam

Belgium · 4 centers

• UZ Antwerpen - Intensive Care — Edegem
• Centre Hospitalier Universitaire (CHU) de Liege - Domaine Universitaire du Sart Tilman - I — Liège
• Clinique Saint-Pierre d'Ottignies - Intensive Care — Ottignies-Louvain-la-Neuve
• Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc - Intensive Ca — Woluwe-Saint-Lambert

Germany · 4 centers

• Klinikum der Universität München AöR - Klinik für Anaesthesiologie (Campus Großhadern) — München
• Kliniken der Stadt Köln gGmbH - Krankenhaus Merheim - Lungenklinik — Cologne
• Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden | Medizini — Dresden
• Universitätsklinikum Leipzig AöR | Interdisziplinare Internistische Intensivmedizin — Leipzig

Identifiers

NCT: NCT06854640 · 22265 · 2024-515635-30-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗