A study evaluating the efficacy, safety and tolerability of Nangibotide in patients with septic shock.

Efficacy, Safety and Tolerability of Nangibotide in Patients with Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study. - ASTONISH

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-004827-36-FR

Enrollment

450

Registered

2019-06-19

Start date

2019-10-07

Completion date

Unknown

Last updated

2022-05-23

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: Nangibotide Pharmaceutical Form: Lyophilisate for solution for infusion INN or Proposed INN: Nangibotide CAS Number: 2014384-91-7 Other descriptive name: LR12 Concentration unit: mg mill

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Provide written informed consent (proxy/legal representative) according to local regulations 2. Age 18 to 85 years (inclusive) Sepsis 3.Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly UTI (=65 years) 4.Organ dysfunction defined as acute change in total SOFA score = 2 points Shock 5. Refractory hypotension requiring vasopressors to maintain MAP =65mm Hg despite adequate volume resuscitation (as per recommendations of the Surviving Sepsis Campaign) 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200

Exclusion criteria

Exclusion criteria: 1. Previous episode of septic shock requiring vasopressor administration within current hospital stay 2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days 3. Immunosuppressive therapy related to recent ( 6 h/day 13. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay) 14. Body mass index (BMI) = 40 kg/m2 or weight = 130 kg 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 randomization

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of two doses of nangibotide on organ dysfunction (Sequential Organ Failure Assessment (SOFA) score) in patients with septic shock in relation to their soluble TREM-1 (sTREM-1) plasma levels (patients with high sTREM-1 levels at baseline or all patients);Secondary Objective: Secondary objectives of the study are to investigate the safety and efficacy of two doses of nangibotide in patients with septic shock in relation to their sTREM-1 levels. This includes: •To evaluate the effect of nangibotide on mortality for up to 12 months •To evaluate the effect of nangibotide on other clinical parameters (e.g. duration of shock, vasopressor use, ventilator and renal replacement use, secondary infections) •To evaluate the safety and tolerability of nangibotide •To evaluate the effect of nangibotide on quality of life, resource utilisation and post shock morbidity •To evaluate the predictive value of the SOFA score reduction as surrogate marker for 28-day ;Primary end point(s): Change of total SOFA score (improvement of organ dysfunction) from baseline to day 3 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population), which will be primarily analyzed on the modified ITT Set.;Timepoint(s) of evaluation of this end point: From baseline to Day 3	—

Measure

Time frame

Main Objective: To evaluate the efficacy of two doses of nangibotide on organ dysfunction (Sequential Organ Failure Assessment (SOFA) score) in patients with septic shock in relation to their soluble TREM-1 (sTREM-1) plasma levels (patients with high sTREM-1 levels at baseline or all patients);Secondary Objective: Secondary objectives of the study are to investigate the safety and efficacy of two doses of nangibotide in patients with septic shock in relation to their sTREM-1 levels. This includes: •To evaluate the effect of nangibotide on mortality for up to 12 months •To evaluate the effect of nangibotide on other clinical parameters (e.g. duration of shock, vasopressor use, ventilator and renal replacement use, secondary infections) •To evaluate the safety and tolerability of nangibotide •To evaluate the effect of nangibotide on quality of life, resource utilisation and post shock morbidity •To evaluate the predictive value of the SOFA score reduction as surrogate marker for 28-day ;Primary end point(s): Change of total SOFA score (improvement of organ dysfunction) from baseline to day 3 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population), which will be primarily analyzed on the modified ITT Set.;Timepoint(s) of evaluation of this end point: From baseline to Day 3

—

Secondary

Measure	Time frame
Secondary end point(s): Key secondary endpoint : • Survival and all-cause mortality on D28; Efficacy Parameters • Duration of ICU stay, hospitalization • Organ support free survival • Sepsis support index (SSI) • Daily change of total SOFA score and individual subscores • Vasopressor use • Invasive mechanical ventilation • Renal support • All-cause mortality up to 12 months • Septic shock related mortality up to 12 months • Incidence of secondary infections and post shock antibiotic use Safety Parameters • Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature • Electrocardiogram (12-lead ECG) • Safety laboratory tests: hematology, coagulation, plasma biochemistry • Presence of anti-nangibotide antibodies • Adverse events (AEs), serious adverse events (SAEs)and deaths Pharmacokinetics • Nangibotide plasma levels Pharmacodynamics (exploratory) • sTREM-1, immune and vascular related biomarkers Pharmacoeconomic Endpoints up to 12 months) • Health related quality of life (EQ 5D) •Post shock morbidity • Health care resource utilization ;Timepoint(s) of evaluation of this end point: • day 28	—

Measure

Time frame

Secondary end point(s): Key secondary endpoint : • Survival and all-cause mortality on D28; Efficacy Parameters • Duration of ICU stay, hospitalization • Organ support free survival • Sepsis support index (SSI) • Daily change of total SOFA score and individual subscores • Vasopressor use • Invasive mechanical ventilation • Renal support • All-cause mortality up to 12 months • Septic shock related mortality up to 12 months • Incidence of secondary infections and post shock antibiotic use Safety Parameters • Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature • Electrocardiogram (12-lead ECG) • Safety laboratory tests: hematology, coagulation, plasma biochemistry • Presence of anti-nangibotide antibodies • Adverse events (AEs), serious adverse events (SAEs)and deaths Pharmacokinetics • Nangibotide plasma levels Pharmacodynamics (exploratory) • sTREM-1, immune and vascular related biomarkers Pharmacoeconomic Endpoints up to 12 months) • Health related quality of life (EQ 5D) •Post shock morbidity • Health care resource utilization ;Timepoint(s) of evaluation of this end point: • day 28

—

Countries

Belgium, Denmark, Finland, France, Ireland, Spain, United States

Contacts

Public ContactValérie Cuvier-Project Manager

INOTREM S.A.

astonish@inotrem.com+33966 81 7900

Outcome results

None listed

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