Adrecizumab Phase 1 Trial

NCT02991508 | Completed Phase 1 DMC

• 2 other identifiers: Adrecizumab-phase12015-005671-24
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is the first clinical trial with ADRECIZUMAB. The purpose of this clinical trial to identify safety and tolerability of different doses of ADRECIZUMAB in healthy volunteers.

Conditions

Healthy Volunteers

Keywords

Adrecizumab; Phase 1 clinical trial; Adrenomedullin; Healthy volunteers; 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 (9)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Vehicle (20 mM His/HCl pH 6.0)

Drug: Placebo

Adrecizumab 0.5 mg/kg

ACTIVE COMPARATOR

To assess the safety, tolerability and pharmacokinetics/-dynamics of single escalating doses of ADRECIZUMAB (0.5 mg/kg, 2,0 mg/kg and 8,0 mg/kg administered as single infusion over 1 hour) in healthy male subjects.

Drug: Adrecizumab

Adrecizumab 2.0 mg/kg

ACTIVE COMPARATOR

To assess the safety, tolerability and pharmacokinetics/-dynamics of single escalating doses of ADRECIZUMAB (0.5 mg/kg, 2,0 mg/kg and 8,0 mg/kg administered as single infusion over 1 hour) in healthy male subjects.

Drug: Adrecizumab

Adrecizumab 8.0 mg/kg

ACTIVE COMPARATOR

To assess the safety, tolerability and pharmacokinetics/-dynamics of single escalating doses of ADRECIZUMAB (0.5 mg/kg, 2,0 mg/kg and 8,0 mg/kg administered as single infusion over 1 hour) in healthy male subjects.

Drug: Adrecizumab

Interventions

Placebo DRUG

Placebo

Adrecizumab DRUG

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, recreational drugs, anti-oxidant 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 1 day prior to the treatment day and during the first 24 hours of the study.
• 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)
• Hypotension (RR systolic \<100 or RR diastolic \<50)
• 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
• CRP above 2x the upper limit of normal or clinically significant acute illness, including infections, within 2 weeks before administration of the study drug.

Sponsors & Collaborators

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

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6500HB, Netherlands

Location

MeSH Terms

Interventions

enibarcimab

Study Officials

• Peter Pickkers, MD, PhD

  Radboudumc department of Intensive Care

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 1, 2016
• First Posted: December 13, 2016
• Study Start: May 23, 2016
• Primary Completion: September 22, 2016
• Study Completion: September 22, 2016
• Last Updated: March 15, 2017

Record last verified: 2017-03

Locations

NL (1)