NCT02629874

Brief Summary

EA-230 is a newly developed synthetic compound with anti-inflammatory properties. Pre-clinical data indicate that EA-230 may be a valuable treatment for systemic inflammation resulting from a variety of causes such as surgery, trauma, infection, irradiation and others. Although previous studies in healthy volunteers have shown an excellent safety profile, the safety and tolerability of higher doses administered per continuous infusion need to be investigated. Also, the dose-effect relation on systemic inflammation needs to be further elucidated before a phase II trial in patients can be commenced.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2015

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

November 16, 2015

Completed
15 days until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

December 14, 2015

Completed
Last Updated

June 23, 2016

Status Verified

June 1, 2016

Enrollment Period

5 months

First QC Date

November 16, 2015

Last Update Submit

June 22, 2016

Conditions

EndotoxemiaSystemic Inflammatory Response

Keywords

EA-230Inflammatory responseKidney InjuryEndotoxemia

Outcome Measures

Primary Outcomes (1)

  • Safety and tolerability expressed in treatment related (serious) adverse events

    Adverse events include: clinically significant variation in vital signs compared to baseline (blood pressure and heart rate), local infusion reaction at site of i.v. IMP infusion, clinically significant changes in ECG compared to baseline and clinically significant deflections in laboratory parameters compared to baseline (Hb, Ht, Leucocytes, thrombocytes, Leucocyte differential blood count, sodium, potassium, creatinine, urea, alkaline phosphatase, ALT, AST, γGT, CK, CRP)

    total (S)AE's at day 14

Secondary Outcomes (9)

  • Cytokines

    at baseline (t=-1.5 and t=0), t=0.5, t=1, t=1,5 t=2, t=3, t=4, t=6, t=8 and t=24 hours after IMP and endotoxin administration

  • Pharmacokinetics - levels of EA-230

    at baseline, t=0.25, t=0.5, t=1, t=1,5 t=2, t=3, t=4, t=6, t=8 and t=24 hours after IMP and endotoxin administration

  • Pharmacokinetics - AUC

    at baseline, t=0.25, t=0.5, t=1, t=1,5 t=2, t=3, t=4, t=6, t=8 and t=24 hours after IMP and endotoxin administration

  • Pharmacokinetics - peak plasma levels

    at baseline, t=0.25, t=0.5, t=1, t=1,5 t=2, t=3, t=4, t=6, t=8 and t=24 hours after IMP and endotoxin administration

  • Pharmacokinetics - half life

    at baseline, t=0.25, t=0.5, t=1, t=1,5 t=2, t=3, t=4, t=6, t=8 and t=24 hours after IMP and endotoxin administration

  • +4 more secondary outcomes

Study Arms (4)

EA-230 (30mg/kg)

ACTIVE COMPARATOR

Subjects will receive EA-230, 30 mg/kg

Drug: EA-230Drug: Endotoxin

EA-230 (90mg/kg)

ACTIVE COMPARATOR

Subjects will receive EA-230, 90 mg/kg

Drug: EA-230Drug: Endotoxin

EA-230 (180mg/kg)

ACTIVE COMPARATOR

Subjects will receive EA-230, 180 mg/kg

Drug: EA-230Drug: Endotoxin

Placebo

PLACEBO COMPARATOR

subjects receive placebo

Drug: EndotoxinDrug: Placebo

Interventions

EA-230DRUG

at t=0 30, 90 or 180 mg/kg EA-230 will be administered intravenously over 2 hours.

Also known as: AQGV
EA-230 (180mg/kg)EA-230 (30mg/kg)EA-230 (90mg/kg)
EndotoxinDRUG

at t=0 2ng/kg purified E.Coli endotoxin is administered intravenously

Also known as: LPS, lipopolysaccharide
EA-230 (180mg/kg)EA-230 (30mg/kg)EA-230 (90mg/kg)Placebo
PlaceboDRUG
Placebo

Eligibility Criteria

Age18 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Aged 18 to 35 years inclusive
  • For part 2 only male
  • Subjects and their partners use a reliable way of contraception
  • BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg
  • Healthy as determined by medical history, physical examination, vital signs, ECG, and clinical laboratory parameters

You may not qualify if:

  • Unwillingness to abstain from any medication, recreational drugs or anti-oxidant vitamin supplements during the course of the study and within 7 days prior to study Day 1.
  • Unwillingness to abstain from nicotine, or alcohol or within 1 day prior to study Day 1
  • Previous participation in a trial where LPS was administered
  • Surgery or trauma with significant blood loss or blood donation within 3 months prior to study Day 1
  • History, signs or symptoms of cardiovascular disease, in particular:
  • History of frequent vaso-vagal collapse or of orthostatic hypotension
  • Resting pulse rate ≤45 or ≥100 beats / min
  • Hypertension (RR systolic \>160 or RR diastolic \>90)
  • Hypotension (RR systolic \<100 or RR diastolic \<50)
  • conduction abnormalities on the ECG
  • Renal impairment: plasma creatinine \>120 µmol/L
  • Liver function tests (alkaline phosphatase, AST, ALT and/or γ-GT) above 2x the upper limit of normal.
  • History of asthma
  • Atopic constitution
  • CRP above 2x the upper limit of normal, or clinically significant acute illness, including infections, within 2 weeks before administration of the study drug.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Intensive care, research unit, Radboud University Medical Centre

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (1)

  • van Groenendael R, Kox M, Leijte G, Koeneman B, Gerretsen J, van Eijk L, Pickkers P. A randomized double-blind, placebo-controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA-230 during experimental human endotoxaemia. Br J Clin Pharmacol. 2019 Jul;85(7):1559-1571. doi: 10.1111/bcp.13941. Epub 2019 May 23.

    PMID: 30919998DERIVED

MeSH Terms

Conditions

Endotoxemia

Interventions

alanyl-glutaminyl-glycyl-valineEndotoxinsLipopolysaccharides

Condition Hierarchy (Ancestors)

BacteremiaSepsisInfectionsToxemiaSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial ToxinsToxins, BiologicalBiological FactorsGlycoconjugatesCarbohydratesPolysaccharides, BacterialPolysaccharidesLipidsAntigens, BacterialAntigens

Study Officials

  • P Pickkers, MD, Prof.

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
prof. dr.

Study Record Dates

First Submitted

November 16, 2015

First Posted

December 14, 2015

Study Start

February 1, 2015

Primary Completion

July 1, 2015

Study Completion

December 1, 2015

Last Updated

June 23, 2016

Record last verified: 2016-06

Locations

NL(1)