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

• ClinicalTrials.gov Identifier: NCT03158948
• Recruitment Status: Completed
• First Posted: May 18, 2017
• Last Update Posted: June 21, 2018
• Sponsor: Inotrem
• Information provided by (Responsible Party): Inotrem

Study Description

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 MOTREM versus placebo in adult patients with septic shock.

Condition or disease	Intervention/treatment	Phase
Shock, Septic	Drug: MOTREM; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomised, Double-blind, Two-Stage, Placebo Controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Doses of MOTREM in Patients With Septic Shock. A Randomised, Double-blind, Two-Stage, Placebo Controlled Study
• Actual Study Start Date: July 3, 2017
• Actual Primary Completion Date: June 13, 2018
• Actual Study Completion Date: June 13, 2018

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo	Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures :

1. Vital signs [ Time Frame: 28 days ]
   systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature (tympanic)
2. ECG [ Time Frame: 28 days ]
   12-lead ECG
3. Number of patients with clinically relevant abnormal laboratory values [ Time Frame: 28 days ]
   Laboratory tests related to hematology, biochemistry and coagulation
4. Presence of anti-LR12 antibodies [ Time Frame: 28 days ]
   Number of patients with anti-LR12 anti drug antibodies
5. Adverse events [ Time Frame: 28 days ]
   Number of patients with adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Belgium

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

Brussels, Belgium

France

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

Limoges Cedex, France

Netherlands

Radboudumc (there may be other sites in this country)

Nijmegen, Netherlands

Spain

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

Madrid, Spain

Sponsors and Collaborators

Inotrem

Investigators

• Principal Investigator: Bruno François, MD; Inserm 1435 Clinical Investigational Center, Limoges, France

More Information

• Responsible Party: Inotrem
• ClinicalTrials.gov Identifier: NCT03158948
• Other Study ID Numbers: MOT-C-201
• First Posted: May 18, 2017
• Last Update Posted: June 21, 2018
• Last Verified: June 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Inotrem:

Sepsis; LR12; TREM1; TREM-1

Additional relevant MeSH terms:

Shock, Septic; Shock; Pathologic Processes; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation