AK1967 (Invobenitug also known as Procizumab)Placebo
AK1967 (Invobenitug also known as Procizumab): DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)
Placebo: Application of placebo
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
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).
Primary outcome measure(s)
Reported number of treatment-emergent adverse events from start of Invobenitug administration up until the last follow-up visit after Invobenitug administration — 30 days
Trial sites (37)
Facility
City
Region
Status
Yerevan medical scientific center
Yerevan
Armenia
Not Yet Recruiting
Erebouni Mwdical Center
Yerevan
Armenia
Not Yet Recruiting
Heart Center Aalst, AZORG
Aalst
Belgium
Recruiting
University Hospital Saint Pierre
Brussels
Belgium
Recruiting
Ghent University Hospital
Ghent
Belgium
Not Yet Recruiting
University Hospital and Medical Faculty of Pilsen
Pilsen
Czechia
Recruiting
Charles University Motol University Hospital
Prague
Czechia
Recruiting
General University Hospital in Prague - FVN
Prague
Czechia
Recruiting
Institute of Clinical and Experimental Medicine - IKEM
Prague
Czechia
Recruiting
University Hospital Avicenne AP-HP
Bobigny
France
Recruiting
Département d'anesthésie-réanimation
Dijon
France
Not Yet Recruiting
University Hospital Lille - Institut Cœur Poumon
Lille
France
Recruiting
University Hospital - Dupuytren Limoges
Limoges
France
Recruiting
Regional University Hospital Nancy - Hopitaux de Brabois
Nancy
France
Recruiting
Hôpital Pitié Salpêtrière
Paris
France
Not Yet Recruiting
Lariboisière Hospital AP-HP
Paris
France
Recruiting
Deutsches Herzzentrum der Charite (DHZC)
Berlin
Germany
Not Yet Recruiting
Universitätsklinikum Freiburg
Freiburg im Breisgau
Germany
Not Yet Recruiting
University Medical Center Hamburg-Eppendorf
Hamburg
Germany
Not Yet Recruiting
Herzzentrum Leipzig GmbH
Leipzig
Germany
Not Yet Recruiting
Universitätsmedizin Mannheim
Mannheim
Germany
Not Yet Recruiting
Radboud University Medical Center
Nijmegen
Netherlands
Recruiting
Uniersytecki Szpital Kliniczny w Białystoku
Bialystok
Poland
Recruiting
Górnośląskie Centrum Medyczne w Katowicach / Śląski Uniwersytet Medyczny w Katowicach
Katowice
Poland
Recruiting
Clinical University Hospital Poznań
Poznan
Poland
Recruiting
J. Mikulicz Radecki Clinical University Hospital Wrocław
Wroclaw
Poland
Recruiting
Clinical Hospital Center Bezanijska Kosa
Belgrade
Serbia
Not Yet Recruiting
Institute for Cardiovascular Diseases of Vojvodina
Kamenitz
Serbia
Not Yet Recruiting
Clinical Center Niš
Niš
Serbia
Not Yet Recruiting
Fundación Pública Galega de Investigación Biomédica INIBIC
A Coruña
Spain
Not Yet Recruiting
Fundació Hospital Universitari Vall d'Hebron
Barcelona
Spain
Not Yet Recruiting
Fundació Hospital Universitari Vall d'Hebron
Barcelona
Spain
Not Yet Recruiting
Hospital Clinic de Barcelona
Barcelona
Spain
Not Yet Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona
Spain
Not Yet Recruiting
L'Hospitalet de Llobregat
Barcelona
Spain
Not Yet Recruiting
Fundación para la Investigación Biomédica del Hospital Universitario La Paz
Madrid
Spain
Not Yet Recruiting
Hospital Universitario 12 De Octubre
Madrid
Spain
Not Yet Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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