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

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

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.

Study Overview

• Status: Completed
• Conditions: Shock, Septic
• Intervention / Treatment: Drug: Placebo; Drug: MOTREM

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc (there may be other sites in this country)
• France
  • Limoges Cedex, France
    • Inserm Clinical Investigational Center, CHU Dupuytren (there may be other sites in this country)
• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc (there may be other sites in this country)
• Spain
  • Madrid, Spain
    • Hospital Clínico San Carlos, Medicina Intensiva (there may be other sites in this country)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; placebo
EXPERIMENTAL: MOTREM 1; 0.3 mg/kg/h	Drug: MOTREM; Formulated LR12 peptide
EXPERIMENTAL: MOTREM 2; 1.0 mg/kg/h	Drug: MOTREM; Formulated LR12 peptide
EXPERIMENTAL: MOTREM 3; 3.0 mg/kg/h	Drug: MOTREM; Formulated LR12 peptide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Inotrem
• Investigators: Principal Investigator: Bruno François, MD, Inserm 1435 Clinical Investigational Center, Limoges, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 3, 2017
• Primary Completion (ACTUAL): June 13, 2018
• Study Completion (ACTUAL): June 13, 2018

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (ACTUAL): May 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Sepsis; LR12; TREM1; TREM-1
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: MOT-C-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No