Invobenitug Also Known as Procizumab (PCZ; AK1967) in Critical Cardiovascular Care

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

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 cDPP3 concentration ≥ 30 ng/mL
3. Etiology of CS must be one of the following: ACS, septic 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 (US: 150 kg).
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 disease 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 such as recent (\<3 months) chemotherapy and/or severe neutropenia (neutrophil 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. US only: Any reason that the investigator anticipates that the patient will be unable to complete the protocol or its required procedures

Conditions2

Interventions2

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