Phase 1 Study to Evaluate Safety, Tolerability and Pharmacokinetics/-Dynamics of AK1967 (Procizumab)

Phase 1 Study on the Safety, Tolerability and Pharmacokinetics/-Dynamics of Escalating Single Intravenous Doses of AK1967 (Procizumab) in Healthy Male Volunteers

Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. During cardiogenic shock, upregulation of the vasoconstrictive molecule angiotensin II is a physiologic and potentially life-saving response aimed at maintaining adequate tissue perfusion. As circulating (c)DPP3 is able to effectively cleave angiotensin II, it may represent a novel factor contributing to hemodynamic instability during cardiogenic shock.

Recently, a cDPP3-antagonizing antibody called AK1967 (commonly referred to as Procizumab) has been developed. In animal models of cardiogenic- and septic shock, inhibition of cDPP3 by AK1967 resulted in improved cardiac function and survival. Furthermore, AK1967 has shown an excellent safety record in different preclinical studies. In the current study the safety, tolerability and pharmacokinetics/-dynamics of AK1967 will be investigated in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Safety and Tolerability
• Intervention / Treatment: Drug: Placebo; Drug: AK1967 (Procizumab)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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 one month after study drug administration.
• BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg and an upper limit of 100 kg.
• Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory parameters.

Exclusion Criteria:

• Unwillingness to abstain from any medication, including recreational drugs or vitamin supplements during the course of the study and within two days prior to the treatment day.
• Unwillingness to abstain from alcohol within one day prior to the treatment day until one day after the treatment day.
• Surgery or trauma with significant blood loss or blood donation within one month 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
• CRP above 2x the upper limit of normal, or clinically significant acute illness, including infections, within two weeks prior to the treatment day.
• Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to the treatment day.
• Known or suspected of not being able to comply with the trial protocol.
• Known hypersensitivity or allergic reactions to drug compounds, (i.e. previous adverse drug reactions).
• Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Application of placebo
Active Comparator: AK1967 3 mg/kg/body weight	Drug: AK1967 (Procizumab); DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)
Active Comparator: AK1967 6 mg/kg/body weight	Drug: AK1967 (Procizumab); DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)
Active Comparator: AK1967 12 mg/kg/body weight	Drug: AK1967 (Procizumab); DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Number of adverse events (AEs)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of AK1967 - t1/2	Pharmacokinetics of AK1967 - t1/2 (Half life)	28-days
Pharmacokinetics of AK1967 - AUC	Pharmacokinetics of AK1967 - Area Under the Curve	28 days

Collaborators and Investigators

• Sponsor: 4TEEN4 Pharmaceuticals GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Actual): August 5, 2024
• Study Completion (Actual): September 4, 2024

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 24, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: procizumab
• Other Study ID Numbers: PCZ_Phase1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No