Invobenitug (procizumab) for cardiogenic shock care

Multi-center, Randomized, Placebo-controlled, Double-blind Phase 1b/2a Trial to Investigate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of Invobenitug Also Knows as Procizumab (PCZ; AK1967) in Patients With Cardiogenic Shock and Elevated Circulating Dipeptidyl Peptidase 3 (cDPP3) Concentrations

This trial will test procizumab (Invobenitug) to see if it is safe and tolerated in adults with cardiogenic shock who need vasopressors and have high cDPP3 levels.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: 4TEEN4 Pharmaceuticals GmbH (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone, procizumab
• Locations: 20 sites (Yerevan and 19 other locations)
• Trial ID: NCT06832722 on ClinicalTrials.gov

What this trial studies

This Phase 1b interventional trial gives procizumab (AK1967) or placebo to adults with cardiogenic shock to measure safety, tolerability, and drug behavior in the body. Participants must have ongoing vasopressors/inotropes to maintain blood pressure, lactate ≥2.0 mmol/L, and cDPP3 ≥30 ng/mL, and be enrolled early in their ICU course. The study collects pharmacokinetic and pharmacodynamic data to define an optimal Phase 2 dose. Patients on certain therapies or with prolonged shock, recent stroke, extreme frailty, or very limited life expectancy are excluded.

Who should consider this trial

Good fit: Adults aged 18–80 with cardiogenic shock who require vasopressors or inotropes, have lactate ≥2.0 mmol/L and cDPP3 ≥30 ng/mL, and who can be enrolled within the early hours of shock are the intended candidates.

Not a fit: Patients who have been on vasopressors/inotropes for more than 16 hours, who have been in the ICU longer than 24 hours, are on Ang II or levosimendan, have recent stroke or SCAI stage E, extreme frailty, or very limited life expectancy are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, procizumab could offer a new targeted therapy that stabilizes patients and may improve outcomes in cardiogenic shock.

How similar studies have performed: Targeting cDPP3 with a monoclonal antibody is a relatively novel approach with encouraging preclinical and limited early-phase data but no established proof of clinical benefit yet in cardiogenic shock.

Eligibility criteria

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.
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

Where this trial is running

Yerevan and 19 other locations

• 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)
• 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)
• 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)

Study contacts

• Principal investigator: Alexandre Mebazaa, Professor — Hôpital Lariboisière, Paris France
• Study coordinator: Karakas Mahir, Prof. Dr. Dr.

Conditions Shock, Cardiogenic; Cardiogenic shock; Procizumab