Shock, Cardiogenic
Conditions
Keywords
Cardiogenic shock, Procizumab, invobenitug
Brief 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.
Interventions
DRUGAK1967 (Invobenitug also known as Procizumab)
DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)
DRUGPlacebo
Application of placebo
Sponsors
4TEEN4 Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 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).
Design outcomes
Primary
| 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 | 30 days |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics defined as plasma-time concentration of invobenitug | 30 days |
| Pharmacodynamics defined as cDPP3 concentration | 30 days |
| Pharmcodynamics defined as cDPP3 activity | 30 days |
Countries
Armenia, Belgium, Czechia, France, Germany, Netherlands, Poland, Serbia, Spain
Contacts
CONTACTKarakas Mahir, Prof. Dr. Dr.
CONTACTPeter Szecsödy, MD
PRINCIPAL_INVESTIGATORAlexandre Mebazaa, Professor
Hôpital Lariboisière, Paris France
PRINCIPAL_INVESTIGATORDavid A. Morrow, MD, MPH
TIMI study Group (An ARO of Brigham & Women's Hospital and an Affiliate of Harvard Medical School)
Outcome results
None listed