Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Doses of MOTREM in Patients With Septic Shock

Study Overview
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Brief Summary
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This is a randomised, double-blind, two-stage, placebo controlled study. It is designed to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of 3 doses of MOTREM versus placebo in adult patients with septic shock.

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

Conditions
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Shock, Septic

Intervention / Treatment
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* Drug: MOTREM
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent (proxy/legal representative) according to local regulations Age 18 to 80 years Documented or suspected infection: lung, abdominal or elderly UTI (≥65 years) Organ dysfunction defined as acute change in SOFA score ≥ 2 points Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation of at least 20 ml/kg within 6 hours 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: - Previous episode of septic shock (vasopressor administration) within current hospital stay Underlying concurrent immunodepression (specified in appendix 2) Solid organ transplant requiring immunosuppressive therapy Known pregnancy (positive serum pregnancy test) Prolonged QT syndrome (QTc ≥ 440 ms) Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding Ongoing documented or suspected endocarditis, history of prosthetic heart valves End-stage neurological disease End-stage cirrhosis (Child Pugh Class C) Acute Physiology And Chronic Health Evaluation (APACHE) II score ≥ 34 End stage chronic renal disease requiring chronic dialysis Home oxygen therapy on a regular basis for > 6 h/day Severe obesity (BMI ≥ 40) Recent CPR (within current hospital stay) Moribund patients Decision to limit full care taken before obtaining informed consent Participation in another interventional study in the 3 months prior to randomisation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, Double-blind, Two-Stage, Placebo Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOTREM 1<br>0.3 mg/kg/h | Drug: MOTREM<br>* Formulated LR12 peptide<br>|
| Experimental: MOTREM 2<br>1.0 mg/kg/h | Drug: MOTREM<br>* Formulated LR12 peptide<br>|
| Experimental: MOTREM 3<br>3.0 mg/kg/h | Drug: MOTREM<br>* Formulated LR12 peptide<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs | systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature (tympanic) | 28 days | 
| ECG | 12-lead ECG | 28 days | 
| Number of patients with clinically relevant abnormal laboratory values | Laboratory tests related to hematology, biochemistry and coagulation | 28 days | 
| Presence of anti-LR12 antibodies | Number of patients with anti-LR12 anti drug antibodies | 28 days | 
| Adverse events | Number of patients with adverse events | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, LR12, TREM1, TREM-1