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

NCT03158948 | Completed Phase 2 Results DMC

• 1 other identifier: MOT-C-201
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 4

Brief Summary

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 nangibotide versus placebo in adult patients with septic shock.

Conditions

Shock, Septic

Keywords

Sepsis; LR12; TREM1; TREM-1

Outcome Measures

Primary Outcomes (9)

• Number of Patients Experiencing Treatment Emergent Adverse Events From Screening Until Study Completion

  Analyses were performed in the Safety Set composed of all randomized patients who received at least any dose of the study drug (nangibotide or placebo). Adverse events: Summary statistics of treatment emergent adverse events (TEAEs). Clinical events, including death, related to severe sepsis and sepsis complications were exempt from SAE reporting, unless the investigator deemed the event to be related to the administration of the study drug.

  Adverse events experienced until D28 (End of study visit)

• Systolic Blood Pressure (SBP)

  Systolic blood pressure measured by sphygmomanometer at study site. Median SBP at each visit is summarized by treatment group.

  Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5) and on final study day at day 28 (D28).

• Diastolic Blood Pressure (DBP)

  Median DBP at each visit is summarized by treatment group.

  Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5) and on final study day at day 28 (D28).

• Median Arterial Pressure (MAP)

  MAP at each visit is summarized by treatment group.

  Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5) and on final study day at day 28 (D28).

• Heart Rate

  Median heart rate at each visit is summarized by treatment group.

  Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5).

• Temperature

  Median temperature at each visit is summarized by treatment group.

  Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5).

• Electrocardiogram

  Abnormal and emergent clinically significant electrocardiogram were summarized for each group.

  Electrocardiogram was performed each day from D0 (before IMP initiation) to D5 (EOI) and on D28 (EOS).

• Anti-Drug Antibodies (ADA Dimer)

  Anti-Drug Antibodies test was performed for all patients.

  Anti-Drug Antibodies test were done at D0, D10 and D28 in all patients.

• Anti-Drug Antibodies (ADA Monomer)

  Anti-Drug Antibodies test was performed for all patients.

  Anti-Drug Antibodies test were measured at D0, D10 and D28.

Secondary Outcomes (5)

• Pharmacokinetic Parameters From the Non-compartmental Analysis: Cmax

  Baseline: pre-dose sample at Day 0 (D0) Daily up to Day 5 (D5) (or the last day in the study/EOI) If possible, at D5/EOI: - 15 min before end of infusion (EOI) - 10 min after EOI - 30 min after EOI - 2h after EOI

• Pharmacokinetic Parameters From the Non-compartmental Analysis: Tmax

  Baseline: pre-dose sample at Day 0 (D0) Daily up to Day 5 (D5) (or the last day in the study/EOI) If possible, at D5/EOI: - 15 min before end of infusion (EOI) - 10 min after EOI - 30 min after EOI - 2h after EOI

• Pharmacokinetic Parameters From the Non-compartmental Analysis: AUC0-last

  Baseline: pre-dose sample at Day 0 (D0) Daily up to Day 5 (D5) (or the last day in the study/EOI) If possible, at D5/EOI: - 15 min before end of infusion (EOI) - 10 min after EOI - 30 min after EOI - 2h after EOI

• Pharmacokinetic Parameters From the Non-compartmental Analysis: Cavg

  Baseline: pre-dose sample at Day 0 (D0) Daily up to Day 5 (D5) (or the last day in the study/EOI) If possible, at D5/EOI: - 15 min before end of infusion (EOI) - 10 min after EOI - 30 min after EOI - 2h after EOI

• Pharmacokinetic Parameters From the Non-compartmental Analysis: CL

  Baseline: pre-dose sample at Day 0 (D0) Daily up to Day 5 (D5) (or the last day in the study/EOI) If possible, at D5/EOI: - 15 min before end of infusion (EOI) - 10 min after EOI - 30 min after EOI - 2h after EOI

Study Arms (4)

nangibotide 0.3 mg/kg/h

EXPERIMENTAL

Drug: Nangibotide 0.3 mg/kg

nangibotide 1.0 mg/kg/h

EXPERIMENTAL

Drug: Nangibotide 1 mg/kg

nangibotide 3.0 mg/kg/h

EXPERIMENTAL

Drug: Nangibotide 3 mg/kg

Placebo to nangibotide

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Nangibotide 0.3 mg/kg DRUG

Formulated LR12 peptide

Also known as: MOTREM 0.3 mg/kg

nangibotide 0.3 mg/kg/h

Placebo DRUG

placebo

Placebo to nangibotide

Nangibotide 1 mg/kg DRUG

Formulated LR12 peptide

Also known as: MOTREM 1 mg/kg

nangibotide 1.0 mg/kg/h

Nangibotide 3 mg/kg DRUG

Formulated LR12 peptide

Also known as: MOTREM 3 mg/kg

nangibotide 3.0 mg/kg/h

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inotrem: lead

Study Sites (4)

Cliniques Universitaires Saint-Luc (there may be other sites in this country)

Brussels, Belgium

Location

Inserm Clinical Investigational Center, CHU Dupuytren (there may be other sites in this country)

Limoges, France

Location

Radboudumc (there may be other sites in this country)

Nijmegen, Netherlands

Location

Hospital Clínico San Carlos, Medicina Intensiva (there may be other sites in this country)

Madrid, Spain

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

nangibotide

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Limitations and Caveats

None reported.

Results Point of Contact

• Title: Executive VP Research and Medical Sciences
• Organization: INOTREM SA

jjg@inotrem.com

30 62 86 51

Study Officials

• Bruno François, MD

  Inserm 1435 Clinical Investigational Center, Limoges, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised, Double-blind, Two-Stage, Placebo Controlled

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: July 3, 2017
• Primary Completion: June 13, 2018
• Study Completion: June 13, 2018
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (1); NL (1); ES (1)