A phase I trial evaluating the safety, tolerability and pharmacokinetics of intravenously administered M6229 in critically ill sepsis patients - *HistoSeps*

Completed

• Conditions: Sepsis; severe infection leading to organ dysfunction; 10019815

• Registration Number: NL-OMON51932
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 11 June 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 26

Inclusion Criteria

1. Male or female patients aged >= 18 year.
2. Signed informed consent by patient or legal representative.
3. Diagnosed with sepsis, defined by the Sepsis-3 criteria as a
life-threatening organ dysfunction caused by a dysregulated host response to an
infection.
4. 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

1. Subject has an advance directive to withhold life-sustaining treatments.
2. Subject is breastfeeding or intents to get pregnant within 30 days of
enrolling into the study.
3. 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.
4. Clinical suspicion or confirmation of a viral hemorrhagic shock syndrome
including, but not limited to, dengue fever.
5. 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).
6. Use of any of the following treatments:
a. UFH to treat a thrombotic event within 12 hours before infusion;
b. LMWH within 24 hours before the infusion;
c. Warfarin (if used within 7 days before study entry AND if the INR
exceeds 2.0 at enrolment);
d. Direct oral anticoagulant (DOAC) use 3 days prior to enrollment.
e. Thrombolytic therapy within 3 previous days;
f. Use of IIb/IIIa inhibitors within the previous 7 days.
7. Confirmed antiphospholipid syndrome.
8. Known allergy to fish.
9. Cardiopulmonary resuscitation in the previous 7 days.
10. Liver failure defined as Child-Pugh Score Class C [19].
11. Abnormal liver function (ASAT and/or ALAT > 5 times upper limit of normal
(ULN)).
12. Extracorporeal membrane oxygenation (ECMO) support dependent.
13. Pulmonary embolism or clinical suspicion of deep venous thrombosis (DVT).
14. Life expectancy of less than 24 hours.
15. Treating physician refusal.
16. Known adverse reaction to UFH, including heparin induced thrombocytopenia
(HIT).
17. Participation in any other investigational drug study or other
interventional study with interfering endpoints.
18. Any other clinical condition which, in the opinion of the investigator,
would not allow safe completion of the protocol.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety:<br /><br>1. Anti-coagulation effects of M6229 determined by a change in aPTT at<br /><br>different time points during and after infusion of M6229.<br /><br><br /><br>Pharmacokinetics:<br /><br>1. Plasma pharmacokinetic parameters of M6229. The following pharmacokinetic<br /><br>parameters will be determined by non-compartmental analysis: Cmax, Css,Tmax,<br /><br>AUC, Clearance, terminal half-life and volume of distribution.<br /><br><br /><br>Efficacy:<br /><br>1. Change in histone plasma levels before and at different time-points after<br /><br>M6229 administration.</p><br>