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

July 4, 2024 updated by: Inotrem

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 nangibotide versus placebo in adult patients with septic shock.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was a randomised, double-blind, two-stage, placebo-controlled study. It was composed of 2 stages with a similar treatment regimen in which 0.3, 1.0 or 3.0 mg/kg/h of nangibotide was tested versus placebo.

Stage 1 was performed to investigate ascending doses of nangibotide or placebo in a sequential design in cohorts of 4 patients (3:1 randomisation). After completion of a cohort (for up to 5 days of infusion), safety and available PK data were blindly reviewed by an independent data safety monitoring board (DSMB) before progressing to the next cohort. After completion of stage 1 DSMB evaluation, the study progressed to stage 2.

Stage 2 investigated 3 doses of nangibotide in a randomised, balanced, parallel-group design involving up to 3 doses of nangibotide and a placebo arm. Only dose arms of nangibotide considered to be safe and well tolerated during Stage 1 were to be administered in Stage 2.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: nangibotide 0.3 mg/kg/h
Drug: Nangibotide 0.3 mg/kg
Formulated LR12 peptide
Other Names:
  • MOTREM 0.3 mg/kg
Experimental: nangibotide 1.0 mg/kg/h
Drug: Nangibotide 1 mg/kg
Formulated LR12 peptide
Other Names:
  • MOTREM 1 mg/kg
Experimental: nangibotide 3.0 mg/kg/h
Drug: Nangibotide 3 mg/kg
Formulated LR12 peptide
Other Names:
  • MOTREM 3 mg/kg
Placebo Comparator: Placebo to nangibotide
Drug: Placebo
placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Patients Experiencing Treatment Emergent Adverse Events From Screening Until Study Completion
Time Frame: Adverse events experienced until D28 (End of study visit)

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)
Time Frame: 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).
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)
Time Frame: 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 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)
Time Frame: 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).
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
Time Frame: Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5).
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
Time Frame: Vital signs were assessed each day from day zero (D0 [before investigational medicinal product initiation]) to end of infusion at day 5 (D5).
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
Time Frame: Electrocardiogram was performed each day from D0 (before IMP initiation) to D5 (EOI) and on D28 (EOS).
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)
Time Frame: Anti-Drug Antibodies test were done at D0, D10 and D28 in all patients.
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)
Time Frame: Anti-Drug Antibodies test were measured at D0, D10 and D28.
Anti-Drug Antibodies test was performed for all patients.
Anti-Drug Antibodies test were measured at D0, D10 and D28.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic Parameters From the Non-compartmental Analysis: Cmax
Time Frame: 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
As no pharmacokinetic sample was planned just after the loading dose, maximum observed nangibotide plasma concentration (Cmax) was in the same magnitude as steady-state concentration during the maintenance infusion, calculated as the median of the observed pre-dose concentration from day2 onwards up to the last pre-dose concentration available in the study (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: Tmax
Time Frame: 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
Time to reach the maximum observed nangibotide plasma concentration (h) was measured for all groups.
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
Time Frame: 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
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration Clast was calculated using the log-linear trapezoidal method.
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
Time Frame: 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
Steady-state concentration during the maintenance infusion was calculated as the median of the observed pre-dose concentration from day2 onwards up to the last pre-dose concentration available in the study.
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
Time Frame: 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
Systemic clearance was calculated as the ratio between the infusion rate during the maintenance infusion and 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Inotrem

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bruno François, MD, Inserm 1435 Clinical Investigational Center, Limoges, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 3, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 13, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 13, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 16, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MOT-C-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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