Healthy VolunteersPhase 1NCT02991508
Adrecizumab Phase 1 Trial
A Phase 1 study testing Adrecizumab in people with Healthy Volunteers, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Adrecizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 May 2016to 22 Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
- Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration.
- Known or suspected of not being able to comply with the trial protocol.
- Known hypersensitivity to any excipients of the drug formulations used. Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Double-blind Placebo-controlled Phase 1 Study on the Safety, Tolerability and Pharmacokinetics/-Dynamics of Escalating Single Intravenous Doses of ADRECIZUMAB (HAM8101) in Healthy Male Subjects
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.
Read the detailed description
Adrenomedullin (ADM) is a natural occurring 52 amino acid peptide which is mainly expressed in endothelial and smooth muscle cells. ADM plasma levels are increased in patients with sepsis and related with severity of disease. ADM is a key regulator of vasotonus and of endothelial integrity in sepsis.
ADRECIZUMAB is an antibody against the N-terminus of ADM which only partially inhibits the bioactivity of ADM. Several septic animal studies have shown that administration of ADRECIZUMAB leads to reduced catecholamine demand, improved renal function, improved fluid balance and improved survival.
The administration of ADRECIZUMAB to rodents and non-human primates (NHP) has been tolerated very well. Single dose and repeated administrations over 14 days to rats and NHP in the GLP toxicology and safety study have not shown any clinical side-effects or histopathological findings.
Based on these data the starting dose for human beings should be 0.5 mg/kg ADRECIZUMAB as single infusion over 1 hour and should be increased up to 8 mg/kg.
- Conditions
- Healthy Volunteers
- Being tested
- Placebo, Adrecizumab
- Keywords
- Adrecizumab, Phase 1 clinical trial, Adrenomedullin, Healthy volunteers, Monoclonal recombinant antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
AdrecizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Vehicle (20 mM His/HCl pH 6.0) Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Adrecizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months follow-up period
Secondary outcomes (9)
Area under the curve (AUC) of free Adrecizumab (pharmacokinetics)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Ex vivo cytokine production
Whole blood will be stimulated with LPS after which cytokine production will be determined by ELISA.
Measured: T=0 hours, T=1 hours, T=8 hours, T=7 days, T=14 days, T=28 days, T=90 days.
Blood levels of norepinephrin, epinephrine, dopamine and renin
Measured: 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.
Blood levels of endothelin and pro-enkephalin.
Measured: T=0, T=0.25, T=0.5, T=1, T=1,5, T=2, T=3, T=4, T=8, T=24 hours. T=7, T=14, T=28, T=60, T=90 days.
Plasma levels of adrenomedullin and MR-proadrenomedullin
Measured: T=0, T=0.25, T=0.5, T=1, T=1,5, T=2, T=3, T=4, T=8, T=24 hours. T=7, T=14, T=28, T=60, T=90 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2016 (estimated)
- Study start23 May 2016
- Primary completion22 Sep 2016
- Study completion22 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Adrenomed AG
- Responsible party
- Principal investigator, Peter Pickkers, Radboud University Medical Center
- Investigators
- Peter Pickkers, MD, PhD, Principal investigator, Radboudumc department of Intensive Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02991508
- Sponsor's protocol ID
- Adrecizumab-phase1
- Other IDs
- 2015-005671-24, 2015
- Status last verified
- Mar 2017
- First submitted
- 1 Jul 2016
- Last updated
- 15 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind Placebo-controlled Phase 1 Study on the Safety, Tolerability and Pharmacokinetics/-Dynamics of Escalating Single Intravenous Doses of ADRECIZUMAB (HAM8101) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02991508
- Acronym / sponsor ID
- Adrecizumab-phase1
- Conditions
- Healthy Volunteers
- Keywords
- Adrecizumab, Phase 1 clinical trial, Adrenomedullin, Healthy volunteers, Monoclonal recombinant antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Adrenomed AG
- Study start
- 23 May 2016 (actual)
- Primary completion
- 22 Sep 2016 (actual)
- Study completion
- 22 Sep 2016 (actual)
- First posted
- 13 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Adrenomedullin (ADM) is a natural occurring 52 amino acid peptide which is mainly expressed in endothelial and smooth muscle cells. ADM plasma levels are increased in patients with sepsis and related with severity of disease. ADM is a key regulator of vasotonus and of endothelial integrity in sepsis.
ADRECIZUMAB is an antibody against the N-terminus of ADM which only partially inhibits the bioactivity of ADM. Several septic animal studies have shown that administration of ADRECIZUMAB leads to reduced catecholamine demand, improved renal function, improved fluid balance and improved survival.
The administration of ADRECIZUMAB to rodents and non-human primates (NHP) has been tolerated very well. Single dose and repeated administrations over 14 days to rats and NHP in the GLP toxicology and safety study have not shown any clinical side-effects or histopathological findings.
Based on these data the starting dose for human beings should be 0.5 mg/kg ADRECIZUMAB as single infusion over 1 hour and should be increased up to 8 mg/kg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboVehicle (20 mM His/HCl pH 6.0) |
| Adrecizumab 0.5 mg/kg | Active comparator | Drug: AdrecizumabTo 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. |
| Adrecizumab 2.0 mg/kg | Active comparator | Drug: AdrecizumabTo 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. |
| Adrecizumab 8.0 mg/kg | Active comparator | Drug: AdrecizumabTo 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
- Renal impairment: plasma creatinine >120 µmol/L
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo | Drug | Placebo |
| Adrecizumab | Drug | Adrecizumab 0.5 mg/kg, Adrecizumab 2.0 mg/kg, Adrecizumab 8.0 mg/kg |
Primary outcome
Safety and tolerability expressed in total number of treatment related (serious) adverse events
Time frame: 3 months follow-up period
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.
9 secondary outcomes
Area under the curve (AUC) of free Adrecizumab (pharmacokinetics)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Ex vivo cytokine production
Time frame: T=0 hours, T=1 hours, T=8 hours, T=7 days, T=14 days, T=28 days, T=90 days.
Blood levels of norepinephrin, epinephrine, dopamine and renin
Time frame: 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.
Blood levels of endothelin and pro-enkephalin.
Time frame: T=0, T=0.25, T=0.5, T=1, T=1,5, T=2, T=3, T=4, T=8, T=24 hours. T=7, T=14, T=28, T=60, T=90 days.
Plasma levels of adrenomedullin and MR-proadrenomedullin
Time frame: T=0, T=0.25, T=0.5, T=1, T=1,5, T=2, T=3, T=4, T=8, T=24 hours. T=7, T=14, T=28, T=60, T=90 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Pickkers, MD, PhD principal investigator
Radboudumc department of Intensive Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adrecizumab in people with Healthy Volunteers, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability expressed in total number of treatment related (serious) adverse events (time frame: 3 months follow-up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.