Clinical trial NCT06832722: Procizumab (PCZ; AK1967) in Critical Cardiovascular Care
Official title: Multi-center, Randomized, Placebo-controlled, Double-blind Phase 1bTrial to Investigate Safety, Tolerability and Pharmacokinetics of Procizumab (PCZ; AK1967) in Patients With Cardiogenic Shock and Elevated Circulating Dipeptidyl Peptidase 3 (cDPP3) Concentrations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Shock, Cardiogenic
Keywords: Cardiogenic shock
Procizumab
Lead sponsor: 4TEEN4 Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2025-02-18
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this Phase 1b trial is to evaluate the safety and tolerability of 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 procizumab are evaluated to define the optimum phase 2 dose (P2D) of procizumab.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent.
* Diagnosis of CS due to ACS or CS of septic origin based on the following entry criteria:

  1. Need for ongoing vasopressors to maintain a MAP ≥ 65 mm ≥ or SBP ≥ 90 mmHg
  2. Serum lactate ≥ 2.0 mmol/L
  3. Elevated DPP3 concentration

Exclusion Criteria:

* Patients who will be receiving vasopressors for more than 16 hours prior to receiving the IMP.
* Patients below the age of 18 or above 75 years.
* Patients receiving Ang II and/or Levosimendan.
* Patients receiving only inotropes for the treatment of CS.
* 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 to treatment 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 and with a high likelihood of requiring MCS within 12 hours of trial enrollment. MCS includes any type of mechanical support device including IAoBP, left ventricular assist device of any type or kind and renal replacement or mechanical 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 at randomization.
* Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated 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 device implantation, 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 ventricular tachycardia or ventricular fibrillation) or ICD shock within the past month or history 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 left ventricular dysfunction.
* Known severe renal disease before admission requiring dialysis or known eGFR prior to 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.
* In those with CS due to ACS, patients with no attempt or failed attempts to coronary revascularization.
* Patients with untreated sepsis.
* Patients with severe valvular heart diseases. This includes any moderate or severe stenotic valvular disease, any moderate or severe aortic or pulmonary regurgitation and severe mitral or tricuspid regurgitation.
* Patients experiencing hemorrhagic, hypovolemic, obstructive, anaphylactic shock or shock related to intoxication or any other reason for shock besides ischemic or septic/ inflammatory causes.
* Patients who have undergone chemotherapy within 30 days prior to trial entry.
* Patients receiving chronic corticosteroid treatment equivalent to a prednisone dose of 10 mg or higher per day, or an equivalent dose of another corticosteroid or any other anti-inflammatory or inflammation suppressing medications such as interleukin blockers, methotrexate or other such therapies.
* Patients who have undergone any form of surgery in the last 7 days will be excluded from the trial or analysis, except 1) minor surgeries such as cosmetic surgeries, skin surgery and dental surgery and 2) primary post operative peritonitis, which are allowed.
* Women who are pregnant or breastfeeding.
* Patients who are currently enrolled in another clinical trial, or who have participated in such trials within one month prior to randomization.

Primary outcomes:
measure: Reported number of treatment-emergent adverse events from start of Procizumab administration up until the last follow-up visit after Procizumab administration
timeFrame: 30 days
Secondary outcomes:
measure: Pharmacokinetics defined as plasma-time concentration of procizumab
timeFrame: 30 days
measure: Pharmacodynamics defined as cDPP3 concentration
timeFrame: 30 days
measure: Pharmcodynamics defined as cDPP3 activity
timeFrame: 30 days
Other outcomes:
Locations:
Study officials:
affiliation: Hôpital Lariboisière, Paris France
name: Alexandre Mebazaa, Professor
role: PRINCIPAL_INVESTIGATOR
References: