Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Doses of MOTREM in Patients with Septic Shock. A Randomised, Double-blind, Two-stage, Placebo Controlled Study.

Phase 2

Completed

• Conditions: Intensive care - septic shock; Blood infection; complication of Sepsis leading to life threatening drop in blood pressure

• Registration Number: NL-OMON45445
• Lead Sponsor: INOTREM S.A

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

1. Provide written informed consent (proxy/legal representative/independent physician/emergency consent) according to local regulations
2. Age 18* to 80 years
* 16 to 80 years in the Netherlands
Sepsis
3. Documented or suspected infection: lung, abdominal or elderly UTI (*65 years)
4. Organ dysfunction defined as acute change in SOFA score * 2 points
Shock
5. Refractory hypotension requiring vasopressors to maintain MAP *65mm Hg despite adequate volume resuscitation of at least 20 ml/kg within 6 hours (according to Surviving Sepsis guidelines, see Appendix 1)
6. Hyperlactatemia (blood lactate >2 mmol/l or 18 mg/dl). This criterion must be met at least once for the purpose of diagnosis within the 24 hours before study drug administration

Exclusion Criteria

1. Previous episode of septic shock (vasopressor administration) within current hospital stay
2. Underlying concurrent immunodepression (specified in appendix 2)
3. Solid organ transplant requiring immunosuppressive therapy
4. Known pregnancy (positive serum pregnancy test)
5. Prolonged QT syndrome (QTc * 440 ms)
6. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
7. Ongoing documented or suspected endocarditis, history of prosthetic heart valves
8. End-stage neurological disease
9. End-stage cirrhosis (Child Pugh Class C)
10. Acute Physiology And Chronic Health Evaluation (APACHE) II score * 34
11. End stage chronic renal disease requiring chronic dialysis
12. Home oxygen therapy on a regular basis for > 6 h/day
13. Severe obesity (BMI * 40)
14. Recent CPR (within current hospital stay)
15. Moribund patients
16. Decision to limit full care taken before obtaining informed consent
17. Participation in another interventional study in the 3 months prior to randomisation

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability parameters:<br /><br><br /><br>1. Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate,<br /><br>and body temperature (tympanic)<br /><br>2. ECG (12-lead ECG)<br /><br>3. Safety laboratory tests: haematology, coagulation, plasma biochemistry<br /><br>4. Presence of anti-LR12 antibodies<br /><br>5. Adverse events : from screening until study completion</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Pharmacokinetics:<br /><br>Plasma concentrations of LR12 will be measured by a validated LCMS/MS assay and<br /><br>analysed using non-compartmental methods to obtain<br /><br>estimates of the PK parameters.<br /><br><br /><br>Pharmacodynamics (exploratory)<br /><br>The concentration profiles of biomarkers (sTREM-1, immune and vascular related<br /><br>biomarkers) over time and biomarker mRNA levels will<br /><br>be analysed.<br /><br><br /><br>Clinical parameters (exploratory)<br /><br>1. Resolution of organ dysfunction (SOFA score total and individual domains)<br /><br>2. Vasopressor use<br /><br>3. Invasive mechanical ventilation<br /><br>4. Renal support<br /><br>5. Time until shock reversal defined as cessation of vasopressor support for 24<br /><br>hours<br /><br>6. Mortality at day 28 and Day 90</p><br>