Procizumab (PCZ; AK1967) in Critical Cardiovascular Care

Inclusion Criteria:

• Signed informed consent.

• Diagnosis of CS due to ACS or CS of septic origin based on the following entrycriteria:

1. Need for ongoing vasopressors and/or to maintain a MAP ≥ 65 mmHg or SBP ≥ 90mmHg

2. Serum lactate ≥ 2.0 mmol/L

3. Elevated DPP3 concentration

Exclusion Criteria:

• Patients who will be receiving vasopressors and/or inotropes for more than 16 hoursprior to receiving the IMP.

• Patients below the age of 18 or above 75 years.

• Patients receiving Ang II and/or Levosimendan.

• Patients with known allergies or hypersensitivity to the IMP or its excipients (including known lactose hypersensitivity) or any related medication.

• Stroke or transient ischemic attack within the last 3 months.

• SCAI Stage E or most severe SCAI D including circulatory collapse refractory totreatment and/or loss of consciousness.

• Patients with SOFA score 12 and above in Part 1; SOFA score 14 and above in Part 2/3.

• Patients on MCS. MCS includes any type of mechanical support device including IAoBP,left ventricular assist device of any type or kind and renal replacement ormechanical support devices of any type or kind.

• Patients exceeding a maximum body weight of 120 kg.

• CPR lasting more than 15 minutes and the patient is not fully conscious atrandomization.

• Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to beassociated with infiltrative heart disease.

• Shock triggered primarily by a correctable causality such as significant arrhythmia (inclusive of atrial fibrillation as the main reason for admission), severe anemia,pulmonary embolism, exacerbation of chronic obstructive pulmonary disease, or deviceimplantation, or over-diuresis as a cause of hypotension.

• Pericardial constriction or active pericarditis.

• Patients suffering from CS due to myocarditis.

• Significant ventricular arrhythmia prior to screening (such as sustained ventriculartachycardia or ventricular fibrillation) or ICD shock within the past month orhistory of sudden death within the last 6 months.

• CRT, ICD, or pacemaker implantation within the past month.

• Sustained SBP > 120 mmHg during the hour prior to randomization.

• Cor pulmonale or other causes of isolated right-sided HF or not related to leftventricular dysfunction.

• Known severe renal disease before admission requiring dialysis or known eGFR priorto admission < 20 ml/min/1.73 m2.

• Laboratory exclusions:

1. Hemoglobin < 8.5 g/dl

2. Platelet count < 30,000/µl for CS from septic origin

3. Platelet count < 100,000/µl for CS from ACS origin

4. Serum potassium > 5.7 mmol/L or < 3.3 mmol/L

• Severe chronic pulmonary or thyroid disease.

• Patients with untreated sepsis.

• Patients with severe valvular heart diseases. This includes any moderate or severestenotic valvular disease, any moderate or severe aortic or pulmonary regurgitationand severe mitral or tricuspid regurgitation.

• Patients experiencing hemorrhagic, hypovolemic, obstructive, anaphylactic shock orshock related to intoxication or any other reason for shock besides ischemic orseptic/ inflammatory causes.

• Patients who have undergone chemotherapy within 30 days prior to trial entry.

• Patients receiving chronic corticosteroid treatment equivalent to a prednisone doseof 10 mg or higher per day, or an equivalent dose of another corticosteroid or anyother anti-inflammatory or inflammation suppressing medications such as interleukinblockers, methotrexate or other such therapies.

• Patients who have undergone any form of surgery in the last 7 days will be excludedfrom the trial or analysis, except 1) minor surgeries such as cosmetic surgeries,skin surgery and dental surgery and 2) primary post operative peritonitis, which areallowed.

• Women who are pregnant or breastfeeding.

• Patients who are currently enrolled in another clinical trial, or who haveparticipated in such trials within one month prior to randomization.