A Phase I Trial Evaluating the Safety, Tolerability and Pharmacokinetics of Intravenously Administered M6229 in Critically Ill Sepsis Patients - "HistoSeps"

A.P.J. Vlaar2 sites in 1 country10 target enrollmentStarted: April 5, 2022Last updated: February 11, 2025

ConditionsSepsis Septic Shock Critical Illness

DrugsM6229

Overview

Phase: Phase 1
Status: Completed
Sponsor: A.P.J. Vlaar
Enrollment: 10
Locations: 2
Primary Endpoint: Steady state concentration (Css) [Pharmacokinetics]

Overview Study Design Eligibility Criteria Outcomes Investigators Sites Records & Identifiers Similar Trials

Overview

Brief Summary

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality is high and survivors frequently suffer from long-term sequelae. Extracellular histones have been identified as essential mediators in the pathogenesis of sepsis and septic shock. These toxic molecules are released by damaged cells in response to infection and high extracellular levels can induce tissue injury and multiple organ dysfunction syndrome. Extracellular histones can be neutralized by complexation with the new candidate drug called M6229, a non-anticoagulant heparin, allowing the use of elevated dose levels relative to regular unfractionated heparin. This project aims at the roll-out of a first-in-man clinical study in sepsis patients evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effects of intravenously administered M6229 in subjects suffering from sepsis.

Study Design

Study Type: Interventional
Allocation: Na
Intervention Model: Single Group
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•Male or female patients aged ≥ 18 years old.
•Signed informed consent by patient or legal representative.
•Diagnosed with sepsis, defined by the Sepsis-3 criteria as a life-threatening organ dysfunction caused by a dysregulated host response to an infection.
•Organ dysfunction is defined by 1 of the following:
•a. Increase in SOFA score of ≥
•i. The baseline SOFA score can be assumed to be zero in patients not known to have pre-existing organ dysfunction.
•b. Acute kidney injury i. Defined as eGFR \< 15 mL/min. c. Acute respiratory distress syndrome i. Defined by the Berlin criteria. d. The need of mechanical ventilation. e. Alteration in mental status.
•The patients have to be included in the study within 72 hours of ICU admission due to sepsis or within 72 hours after sepsis diagnosis on the ICU. M6229 has to be administered within 84 hours after ICU admission due to sepsis or within 84 hours after sepsis diagnosis on the ICU.

Exclusion Criteria

•Subject has an advance directive to withhold life-sustaining treatments.
•Subject is breastfeeding or intents to get pregnant within 30 days of enrolling into the study.
•Subject is of childbearing potential and has a positive pregnancy test.
•a. A woman is considered to be of childbearing potential under the age of 60 years, unless surgically sterile.
•Clinical suspicion or confirmation of a viral hemorrhagic shock syndrome including, but not limited to, dengue fever.
•Bleeding risk:
•a. Clinical: i. Active bleeding; ii. Head trauma; iii. Intracranial surgery or stroke in the past 3 months; iv. History of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system; v. Cerebral haemorrhage; vi. History of a bleeding diatheses; vii. Gastrointestinal bleeding in the past 6 weeks; viii. Presence of an epidural or spinal catheter; ix. Contraindication for IV therapeutic UFH. b. Laboratory: i. Platelet count \<50 x109/L; ii. INR \>2.0; iii. Baseline aPTT ≥45 seconds prior to enrolment, 1.5x upper limit of normal (ULN).
•Use of any of the following treatments:
•UFH to treat a thrombotic event within 12 hours before infusion;
•LMWH within 24 hours before infusion;