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

Official title

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

Overview

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

• Drug AK1967 (Invobenitug also known as Procizumab)
  DPP3 inhibition using the humanized monoclonal antibody AK1967 (Procizumab)
• Drug Placebo
  Application of placebo

Primary outcome measures

• Reported number of treatment-emergent adverse events from start of Invobenitug administration up until the last follow-up visit after Invobenitug administration [Time frame: 30 days]

Secondary outcome measures (3)

• Pharmacokinetics defined as plasma-time concentration of invobenitug [Time frame: 30 days]
• Pharmacodynamics defined as cDPP3 concentration [Time frame: 30 days]
• Pharmcodynamics defined as cDPP3 activity [Time frame: 30 days]

Eligibility criteria

Inclusion criteria

• Signed informed consent.
• Diagnosis of CS based on the following entry criteria:

• Need for ongoing vasopressors and/or inotropes to maintain a MAP ≥ 65 mmHg or SBP ≥ 90 mmHg
• Lactate ≥ 2.0 mmol/L
• High cDPP3 concentration ≥ 30 ng/mL
• Etiology of CS must be one of the following: ACS, septic or adHF origin

Exclusion criteria

• Patients who will be receiving vasopressors and/or inotropes for more than 16 hours prior to receiving the IMP.
• Patients being longer than 24 hours in the ICU at the time of randomization.
• Patients below the age of 18 or above 80 years.
• Patients receiving Ang II and/or levosimendan.
• Patients with known allergies or hypersensitivity to the IMP or its excipients or any related medication.
• Stroke or transient ischemic attack within the last 3 months.
• SCAI Shock Stage E.
• Reduced life expectancy of less than 6 months due to comorbidities (prior to shock onset).
• Very severe frailty, or moribund condition or presence of clinical circumstances indicating imminent death.
• 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.
• Patients exceeding a maximum body weight of 120 kg (US: 150 kg).
• CPR lasting more than 15 minutes and/or the patient is not conscious at randomization.
• Primary hypertrophic or restrictive cardiomyopathy or congenital heart disease or systemic illness known to be associated with infiltrative heart disease.
• Pericardial constriction
• Sustained SBP > 120 mmHg during the hour prior to randomization.
• 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.
• Patients with untreated sepsis.
• Patients with valvular heart diseases as the primary cause of cardiogenic shock.
• Other known causes of shock, namely

• Hypovolemia
• Hemorrhage
• Anaphylaxis
• Intoxication (e.g., drug-induced shock)
• Dynamic left ventricular outflow tract obstruction
• Isolated right heart failure, including cardiac tamponade and/or pulmonary embolism
• Known mechanical complications due to myocardial infarction, including papillary muscle rupture, ventricular septal rupture, free wall rupture
• Inappropriate pacing or shock resulting from ICD malfunction
• 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
• 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.
• 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
• US only: Any reason that the investigator anticipates that the patient will be unable to complete the protocol or its required procedures

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

France · 7 centers

• University Hospital Avicenne AP-HP — Bobigny
• Département d'anesthésie-réanimation — Dijon
• University Hospital Lille - Institut Cœur Poumon — Lille
• University Hospital - Dupuytren Limoges — Limoges
• Regional University Hospital Nancy - Hopitaux de Brabois — Nancy
• Hôpital Pitié Salpêtrière — Paris
• Lariboisière Hospital AP-HP — Paris

Poland · 5 centers

• Uniersytecki Szpital Kliniczny w Białystoku — Bialystok
• Uniwersytecki Szpital Kliniczny w Białymstoku — Bialystok
• Górnośląskie Centrum Medyczne w Katowicach / Śląski Uniwersytet Medyczny w Katowicach — Katowice
• Clinical University Hospital Poznań — Poznan
• J. Mikulicz Radecki Clinical University Hospital Wrocław — Wroclaw

Czechia · 4 centers

• University Hospital and Medical Faculty of Pilsen — Pilsen
• Charles University Motol University Hospital — Prague
• General University Hospital in Prague - FVN — Prague
• Institute of Clinical and Experimental Medicine - IKEM — Prague

Belgium · 3 centers

• Heart Center Aalst, AZORG — Aalst
• University Hospital Saint Pierre — Brussels
• Ghent University Hospital — Ghent

Serbia · 3 centers

• Clinical Hospital Center Bezanijska Kosa — Belgrade
• Institute for Cardiovascular Diseases of Vojvodina — Kamenitz
• Clinical Center Niš — Niš

Armenia · 2 centers

• Yerevan medical scientific center — Yerevan
• Erebouni Mwdical Center — Yerevan

Netherlands · 1 center

• Radboud University Medical Center — Nijmegen

Publications

• van Lier D, Mourisse L, Hollander H, Santos K, Bergmann A, van Herwaarden AE, Kox M, Pickkers P. Safety, tolerability, and pharmacokinetics/-dynamics of the dipeptidyl peptidase 3-inhibiting antibody Procizumab in a first-in-human trial. MAbs. 2026 Dec;18(1):2671468. doi: 10.1080/19420862.2026.2671468. Epub 2026 May 21. PMID 42165327

Identifiers

NCT: NCT06832722 · CT-P1-002 · 2024-518450-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗