Study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics 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. - N/A

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-005032-14-NL

Enrollment

Registered

2017-04-05

Start date

2017-07-19

Completion date

Unknown

Last updated

2019-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Septic shock MedDRA version: 20.0 Level: PT Classification code 10040070 Term: Septic shock System Organ Class: 10021881 - Infections and infestations

Interventions

Product Name: MOTREM Product Code: MOTREM (LR12) Pharmaceutical Form: Lyophilisate for solution for injection INN or Proposed INN: Nangibotide

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Provide written informed consent (proxy/legal representative) 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 =65 mmHg despite adequate volume resuscitation of at least 20 ml/kg within 6 hours 6. Hyperlactatemia (blood lactate > 2mmol/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 Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5

Exclusion criteria

Exclusion criteria: 1. Previous episode of septic shock (vasopressor administration) within current hospital stay 2. Underlying concurrent immunodepression 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

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the safety and tolerability of MOTREM in patients with septic shock; Secondary Objective: - To evaluate the effects of MOTREM exposure over up to 5 days in patients with septic shock - To evaluate the PK/PD and dose/PD relationship to TREM-1 pathway related makers - To evaluate the effect of MOTREM on transcriptomics - To evaluate the effect of MOTREM on clinical parameters (e.g. vasopressor doses, vasopressor-free days, ventilator-free days, mortality) ; Primary end point(s): Safety and tolerability parameters: 1. Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature (tympanic) 2. ECG (12-lead ECG) 3. Safety laboratory tests: haematology, coagulation, plasma biochemistry 4. Presence of anti-LR12 antibodies 5. Adverse events : from screening until study completion ; Timepoint(s) of evaluation of this end point: 1. Screening, Baseline, Day 1 to Day 5, End of Study 2. Screening, Baseline, Day 1 to Day 5, End of Study 3. Screening, Baseline, Day 1 to Day 5 4. Baseline (pre-dose), End of Infusion and FU day 28 5. From Screening until study completion	—

Measure

Time frame

Main Objective: To evaluate the safety and tolerability of MOTREM in patients with septic shock; Secondary Objective: - To evaluate the effects of MOTREM exposure over up to 5 days in patients with septic shock - To evaluate the PK/PD and dose/PD relationship to TREM-1 pathway related makers - To evaluate the effect of MOTREM on transcriptomics - To evaluate the effect of MOTREM on clinical parameters (e.g. vasopressor doses, vasopressor-free days, ventilator-free days, mortality) ; Primary end point(s): Safety and tolerability parameters: 1. Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature (tympanic) 2. ECG (12-lead ECG) 3. Safety laboratory tests: haematology, coagulation, plasma biochemistry 4. Presence of anti-LR12 antibodies 5. Adverse events : from screening until study completion ; Timepoint(s) of evaluation of this end point: 1. Screening, Baseline, Day 1 to Day 5, End of Study 2. Screening, Baseline, Day 1 to Day 5, End of Study 3. Screening, Baseline, Day 1 to Day 5 4. Baseline (pre-dose), End of Infusion and FU day 28 5. From Screening until study completion

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Secondary

Measure	Time frame
Secondary end point(s): Pharmacokinetics Plasma concentrations of LR12 will be measured by a validated LC-MS/MS assay and analysed using non-compartmental methods to obtain estimates of the PK parameters. Pharmacodynamics (exploratory) The concentration profiles of biomarkers (sTREM-1, immune and vascular related biomarkers) over time and biomarker mRNA levels will be analysed.. Clinical parameters (exploratory) 1. Resolution of organ dysfunction (SOFA score total and individual domains) 2. Vasopressor use 3. Invasive mechanical ventilation 4. Renal support 5. Time until shock reversal defined as cessation of vasopressor support for 24 hours 6. Mortality at day 28 and Day 90 ; Timepoint(s) of evaluation of this end point: PK: Baseline (pre-dose), Day 1 to Day 5 + End of infusion PD: Baseline, Day 1 to Day 5, End of Study Clinical parameters: 1. Screening, Baseline, Day 1 to Day 5, End of Study 2. Baseline, Day 1 to Day 5, End of Study 3. Baseline, Day 1 to Day 5, End of Study 4. Baseline, Day 1 to Day 5, End of Study 5. Cessation of vasopressor support for 24 hours 6. Day 28 and Day 90	—

Measure

Time frame

Secondary end point(s): Pharmacokinetics Plasma concentrations of LR12 will be measured by a validated LC-MS/MS assay and analysed using non-compartmental methods to obtain estimates of the PK parameters. Pharmacodynamics (exploratory) The concentration profiles of biomarkers (sTREM-1, immune and vascular related biomarkers) over time and biomarker mRNA levels will be analysed.. Clinical parameters (exploratory) 1. Resolution of organ dysfunction (SOFA score total and individual domains) 2. Vasopressor use 3. Invasive mechanical ventilation 4. Renal support 5. Time until shock reversal defined as cessation of vasopressor support for 24 hours 6. Mortality at day 28 and Day 90 ; Timepoint(s) of evaluation of this end point: PK: Baseline (pre-dose), Day 1 to Day 5 + End of infusion PD: Baseline, Day 1 to Day 5, End of Study Clinical parameters: 1. Screening, Baseline, Day 1 to Day 5, End of Study 2. Baseline, Day 1 to Day 5, End of Study 3. Baseline, Day 1 to Day 5, End of Study 4. Baseline, Day 1 to Day 5, End of Study 5. Cessation of vasopressor support for 24 hours 6. Day 28 and Day 90

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Countries

Belgium, Netherlands, Spain

Contacts

Public ContactCEO

INOTREM S.A.

jjg@inotrem.com+33(0)6 30 62 86 51

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026