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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (3)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Франция · 7 центров

• 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

Польша · 5 центров

• 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

Чехия · 4 центра

• 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

Бельгия · 3 центра

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

Сербия · 3 центра

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

Армения · 2 центра

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

Нидерланды · 1 центр

• Radboud University Medical Center — Nijmegen

Публикации

• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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