Adrecizumab-LPS Study

NCT03083171 | Completed Phase 1 DMC

• 1 other identifier: Adrecizumab-LPS
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized, double-blind, placebo-controlled study, either a single dose of Adrecizumab (0.5, 2.0 or 8.0 mg/kg) or placebo will be administrated to 24 healthy male volunteers during experimental endotoxemia.

Conditions

Healthy Volunteers

Keywords

Adrecizumab; Adrenomedullin; Healthy volunteers; LPS; Monoclonal recombinant antibody

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability expressed in total number of 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.

  3 months follow-up period

Secondary Outcomes (8)

• Area under the curve (AUC) of free Adrecizumab (pharmacokinetics)

  T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration

• Peak plasma concentration (Cmax) of free Adrecizumab (pharmacokinetics)

  T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration

• Terminal t1/2 of free Adrecizumab (pharmacokinetics)

  T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration

• Clearance of free Adrecizumab (pharmacokinetics)

  T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration

• Volume of distribution of free Adrecizumab (pharmacokinetics)

  T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Endotoxin; Drug: Placebo

Adrecizumab 0.5 mg/kg

ACTIVE COMPARATOR

A single intravenous dose of 0.5 mg/kg Adrecizumab given over a 1 hour period.

Drug: Endotoxin; Drug: Adrecizumab

Adrecizumab 2.0 mg/kg

ACTIVE COMPARATOR

A single intravenous dose of 2.0 mg/kg Adrecizumab given over a 1 hour period.

Drug: Endotoxin; Drug: Adrecizumab

Adrecizumab 8.0 mg/kg

ACTIVE COMPARATOR

A single intravenous dose of 8.0 mg/kg Adrecizumab given over a 1 hour period.

Drug: Endotoxin; Drug: Adrecizumab

Interventions

Endotoxin DRUG

At T=0 1 ng/kg E. Coli type O113 lipopolysaccharide is administrated intravenously as a bolus, followed by 1 ng/kg/hour for 3 hours.

Also known as: LPS, Lipopolysaccharide

Adrecizumab 0.5 mg/kg; Adrecizumab 2.0 mg/kg; Adrecizumab 8.0 mg/kg; Placebo

Placebo DRUG

At T=1 hour, placebo will be administered intravenously over a 1 hour period. Placebo is indistinguishable from Adrecizumab.

Placebo

Adrecizumab DRUG

At T=1 hour, Adrecizumab will be administered intravenously over a 1 hour period.

Adrecizumab 0.5 mg/kg; Adrecizumab 2.0 mg/kg; Adrecizumab 8.0 mg/kg

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent to participate in this trial prior to any study-mandated procedure.
• Male subjects aged 18 to 35 years inclusive.
• Subjects have to agree to use a reliable way of contraception with their partners from study entry until 3 months after study drug administration.
• BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg and a upper limit of 100 kg.
• Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory parameters.

You may not qualify if:

• Unwillingness to abstain from any medication, including recreational drugs or vitamin supplements during the course of the study and within 7 days prior to the treatment day.
• Unwillingness to abstain from smoking, or alcohol, within 1 day prior to the treatment day and 1 day after the treatment day.
• Previous participation in a trial where LPS was administered.
• Surgery or trauma with significant blood loss or blood donation within 3 months prior to the treatment day.
• History, signs or symptoms of cardiovascular disease, in particular:
• History of frequent vasovagal collapse or of orthostatic hypotension
• Resting pulse rate ≤45 or ≥100 beats/min
• Hypertension (RR systolic \>160 or RR diastolic \>90 mmHg)
• Hypotension (RR systolic \<100 or RR diastolic \<50 mmHg)
• Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
• Any chronic cardiac arrhythmias (except PAC's, PVC's)
• 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

Sponsors & Collaborators

• Adrenomed AG: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Dept. of Intensive Care Medicine, Research-unit, Radboud university medical center

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

MeSH Terms

Interventions

Endotoxins; Lipopolysaccharides; enibarcimab

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 17, 2017
• Study Start: January 4, 2017
• Primary Completion: May 24, 2017
• Study Completion: May 24, 2017
• Last Updated: February 1, 2021

Record last verified: 2017-03

Locations

NL (1)