A Phase 1b/2a Trial to Evaluate Invobenitug Also Known as Procizumab (PCZ; AK1967) in Critical Cardiovascular Care. (PROCARD 2a)

September 10, 2026 updated by: 4TEEN4 Pharmaceuticals GmbH

Multi-center, Randomized, Placebo-controlled, Double-blind Phase 1b/2a Trial to Investigate Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy of Invobenitug Also Known as Procizumab (PCZ; AK1967) in Patients With Cardiogenic Shock and Elevated Circulating Dipeptidyl Peptidase 3 (cDPP3) Concentrations.

The objective of this Phase 1b/2a trial is to evaluate the safety, tolerability, and exploratory efficacy of invobenitug (also known as procizumab), a monoclonal antibody under development for the treatment of cardiogenic shock (CS). CS is a life-threatening hypoperfusion of vital organs that frequently results in death. In addition to safety and tolerability, pharmacokinetics and pharmacodynamics of invobenitug are evaluated to define the optimum phase 2 dose (P2D) of invobenitug.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Karakas Mahir, Prof. Dr. Dr.
  • Phone Number: +49 173 3060687
  • Email: karakas@4teen4.de

Study Contact Backup

Study Locations

  • Armenia
      • Yerevan, Armenia, 0014
        • Not yet recruiting
        • Yerevan medical scientific center
        • Contact:
          • Harutyun Ghrmajyan, Dr.
      • Yerevan, Armenia, 0087
        • Not yet recruiting
        • Erebouni Mwdical Center
        • Contact:
          • Hamlet Hayrapetyan
  • Belgium
      • Aalst, Belgium
        • Recruiting
        • Heart Center Aalst, AZORG
        • Contact:
          • Christophe Vandenbriele
      • Brussels, Belgium
      • Ghent, Belgium
        • Not yet recruiting
        • Ghent University Hospital
        • Contact:
          • Hanna Schaubroeck, Dr.
  • Czechia
      • Pilsen, Czechia
        • Recruiting
        • University Hospital and Medical Faculty of Pilsen
        • Contact:
          • Richard Rokyta
      • Prague, Czechia
        • Recruiting
        • General University Hospital in Prague - FVN
        • Contact:
      • Prague, Czechia
        • Recruiting
        • Institute of Clinical and Experimental Medicine - IKEM
        • Contact:
      • Prague, Czechia
        • Recruiting
        • Charles University Motol University Hospital
        • Contact:
          • Petr Ostadal
  • France
      • Bobigny, France
      • Dijon, France, 21000
        • Not yet recruiting
        • Département d'anesthésie-réanimation
        • Contact:
          • Pierre-Grégoire Guinot, PhD, MD
      • Lille, France
        • Recruiting
        • University Hospital Lille - Institut Cœur Poumon
        • Contact:
      • Limoges, France
      • Nancy, France
        • Recruiting
        • Regional University Hospital Nancy - Hopitaux de Brabois
        • Contact:
      • Paris, France, 75651
        • Not yet recruiting
        • Hôpital Pitie Salpétrière
        • Contact:
          • Alain Combes, PhD, MD
      • Paris, France
  • Germany
      • Berlin, Germany
        • Not yet recruiting
        • Deutsches Herzzentrum der Charite (DHZC)
        • Contact:
          • Carsten Skurk, Prof. Dr. med.
      • Freiburg im Breisgau, Germany
        • Not yet recruiting
        • Universitatsklinikum Freiburg
        • Contact:
          • Lucas Bacmeister, Dr. med.
      • Hamburg, Germany
        • Not yet recruiting
        • University Medical Center Hamburg-Eppendorf
        • Contact:
          • Stefan Kluge, Prof. Dr. med.
      • Leipzig, Germany
        • Not yet recruiting
        • Herzzentrum Leipzig GmbH
        • Contact:
          • Holger Thiele, Prof. Dr. med.
      • Mannheim, Germany
        • Not yet recruiting
        • Universitätsmedizin Mannheim
        • Contact:
          • Ibrahim Akin, Prof. Dr. med.
  • Netherlands
  • Poland
      • Bialystok, Poland
        • Recruiting
        • Uniersytecki Szpital Kliniczny w Białystoku
        • Contact:
          • Agnieszka Tycińska
      • Katowice, Poland
        • Recruiting
        • Górnośląskie Centrum Medyczne w Katowicach / Śląski Uniwersytet Medyczny w Katowicach
        • Contact:
          • Maciej Wybraniec
      • Poznan, Poland
      • Wroclaw, Poland
        • Recruiting
        • J. Mikulicz Radecki Clinical University Hospital Wrocław
        • Contact:
  • Serbia
      • Belgrade, Serbia
        • Not yet recruiting
        • Clinical Hospital Center Bezanijska Kosa
        • Contact:
          • Marija Zdravkovic, PhD, MD
      • Kamenitz, Serbia
        • Not yet recruiting
        • Institute for Cardiovascular Diseases of Vojvodina
        • Contact:
          • Sonja Dimic, MD
      • Niš, Serbia
        • Not yet recruiting
        • Clinical Center Niš
        • Contact:
          • Bojan Maricic, Dr.
  • Spain
      • A Coruña, Spain
        • Not yet recruiting
        • Fundación Pública Galega de Investigación Biomédica INIBIC
        • Contact:
          • Miguel Solla-Buceta, Dr.
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital Clinic de Barcelona
        • Contact:
          • Rut Andrea Riba, PhD, MD
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital de La Santa Creu i Sant Pau
        • Contact:
          • Alessandro Sionis, Dr.
      • Barcelona, Spain
        • Not yet recruiting
        • Fundació Hospital Universitari Vall d'Hebron
        • Contact:
          • Ricard Ferrer Roca, PhD, MD
      • Barcelona, Spain
        • Not yet recruiting
        • L'Hospitalet de Llobregat
        • Contact:
          • Albert Ariza-Sole, Dr.
      • Madrid, Spain
        • Not yet recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
          • Roberto Martin, Dr.
      • Madrid, Spain
        • Not yet recruiting
        • Fundación para la Investigación Biomédica del Hospital Universitario La Paz
        • Contact:
          • Isabel Antorrena, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed informed consent.

  2. Diagnosis of CS based on the following entry criteria:

    1. Need for ongoing vasopressors and/or inotropes to maintain a MAP ≥ 65 mmHg or SBP ≥ 90 mmHg
    2. Lactate ≥ 2.0 mmol/L
    3. High DPP3 concentration ≥ 30 ng/mL

  3. Etiology of CS must be one of the following: ACS, septic (according to SEPSIS 3 criteria) or adHF origin

    Exclusion Criteria:

  4. Patients who will be receiving vasopressors and/or inotropes for more than 16 hours prior to receiving the IMP.
  5. Patients being longer than 24 hours in the ICU at the time of randomization.
  6. Patients below the age of 18 or above 80 years.
  7. Patients receiving Ang II and/or levosimendan
  8. Patients with known allergies or hypersensitivity to the IMP or its excipients or any related medication.
  9. Stroke or transient ischemic attack within the last 3 months.
  10. SCAI Shock Stage E.
  11. Reduced life expectancy of less than 6 months due to comorbidities (prior to shock onset).
  12. Very severe frailty, or moribund condition or presence of clinical circumstances indicating imminent death.
  13. Only for Part 1: Patients on cannula-based MCS (including VV and VA-ECMO, impella or left ventricular assist device of any type (excluding IABP)) or on renal replacement therapy. Patients who are treated by impella and/or ECMO but have no evidence of hemolysis during screening can be enrolled in the trial.
  14. Patients exceeding a maximum body weight of 120 kg (EU, Armenia, Serbia) and 150 kg (US).
  15. CPR lasting more than 15 minutes and/or the patient is not conscious at randomization.
  16. Primary hypertrophic or restrictive cardiomyopathy or congenital heart disease or systemic illness known to be associated with infiltrative heart disease.
  17. Pericardial constriction.
  18. Sustained SBP > 120 mmHg during the hour prior to randomization.
  19. Known severe chronic liver disease (Model for End-Stage Liver Disease (MELD) Score >30), known severe chronic pulmonary disease (including COPD classification GOLD4 and/or chronic oxygen therapy and/or restrictive chronic pulmonary failure and/or severe interstitial lung disease), known severe thyroid disease, known CKD with eGFR <20 ml/min/1.73 m2 or chronic dialysis.
  20. Patients with untreated sepsis.
  21. Patients with valvular heart diseases as the primary cause of cardiogenic shock.

  22. Other known causes of shock, namely

    1. Hypovolemia
    2. Hemorrhage
    3. Anaphylaxis
    4. Intoxication (e.g., drug-induced shock)
    5. Dynamic left ventricular outflow tract obstruction
    6. isolated right heart failure, including cardiac tamponade and/or pulmonary embolism
    7. Known mechanical complications due to myocardial infarction, including papillary muscle rupture, ventricular septal rupture, free wall rupture
    8. Inappropriate pacing or shock resulting from ICD malfunction
  23. Patients who have severe immune suppression: recent (<3 months) chemotherapy and/or severe neutropenia (neutrophile count <500 cells/mm3) and/or chronic high glucocorticoid dose (≥0.5 mg/kg per day of prednisone equivalent) and/or recent (<3 months) organ transplantation.
  24. Patients who have undergone any form of surgery in the last 7 days, except 1) minor surgeries such as cosmetic surgeries, skin surgery, dental surgery and impella implantation 2) surgery for peritonitis with adequate source control, which are allowed.
  25. Women who are pregnant or breastfeeding.
  26. Patients who are currently enrolled in another clinical trial, or who have participated in such trials within one month prior to randomization.
  27. Any reason that the investigator anticipates that the patient will be unable to complete the protocol or its required procedures (US only).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Application of placebo
Active Comparator: Invobenitug also known as Invobenitug (AK1967) 10mg/kg body weight
Drug: AK1967 (Invobenitug also known as Procizumab)
DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reported number of treatment-emergent adverse events from start of Invobenitug administration up until the last follow-up visit after Invobenitug administration
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacodynamics defined as cDPP3 concentration
Time Frame: 30 days
30 days
Pharmcodynamics defined as cDPP3 activity
Time Frame: 30 days
30 days
Pharmacokinetics defined as plasma-time concentration of invobenitug
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4TEEN4 Pharmaceuticals GmbH

Investigators

  • Principal Investigator: Alexandre Mebazaa, Professor, Hôpital Lariboisière, Paris France
  • Principal Investigator: David A. Morrow, MD, MPH, TIMI study Group (An ARO of Brigham & Women's Hospital and an Affiliate of Harvard Medical School)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2025

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

February 7, 2025

First Submitted That Met QC Criteria

February 17, 2025

First Posted (Actual)

February 18, 2025

Study Record Updates

Last Update Posted (Actual)

September 14, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-P1-002
  • 2024-518450-16-00 (Ctis)

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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