Hartopo Anggoro Budi, Achyar Arinal Chairul, Bagaswoto Hendry Purnasidha, Saputra Firandi, Mumpuni Hasanah, Kusumastuti Dyah Adhi, Triyono Teguh, Sukorini Usi, Puspitasari Metalia, Setianto Budi Yuli, Rohman Mohammad Saifur, Anshory Muhammad, Waranugraha Yoga, Kamila Putri Annisa, Iskandar Agustin, Susianti Hani, Bergman Andreas, Knothe Claudia, Antonini Paola, Di Somma Salvatore
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia.
ESC Heart Fail. 2025 Jun;12(3):1848-1860. doi: 10.1002/ehf2.15191. Epub 2025 Jan 14.
This study aimed to conduct a phase 2 proof-of-concept and safety study to evaluate the effect of ENIBARCIMAB (EN), a non-neutralizing humanized monoclonal antibody targeting the N-terminus of adrenomedullin (ADM), administered immediately after stabilization with standard of care (SoC) treatment, in patients hospitalized for acute heart failure (AHF).
This prospective, open-label, controlled, interventional, multicenter, dose-escalation study was conducted at two cardiology sites in Indonesia. Patients were divided into two interventional groups sequentially receiving 0.5 mg/kg (SoC + EN 0.5 mg/kg, n = 10; first cohort) and 2 mg/kg (SoC + EN 2 mg/kg, n = 10; second cohort) of EN via 1-h intravenous (IV) infusion within 48 h after admission for AHF. The control group (n = 10) was treated with SoC therapy for AHF therapy. All patients were monitored continuously within 24 h post-infusion and subsequent daily until discharge. Treatment-related serious adverse events (SAEs) were recorded during hospitalization and up to 90 days after discharge. Both EN dosages were well-tolerated, and no significant safety issues were identified during hospitalization and up to 90 days of follow up. SAEs occurred in 10% of patients in each EN group but were deemed not related to treatment. No significant differences in the occurrence of SAEs were found between the groups. Five deaths occurred: three (30%) in the control group as compared with two deaths (20%) in the SoC + EN 2 mg/kg group. EN led to a significant increase in plasma bio-ADM levels within 24 h post-infusion, with the SoC + 2 mg/kg group showing the highest increase. Within 1 h from IV EN infusion, SoC + EN 2 mg/kg compared with 0.5 mg/kg, resulted in a significant percentage reduction in systolic, diastolic blood pressure, and mean arterial pressure. However, it did not result in severe hypotension and the need for drug discontinuation.
In this pilot safety study of patients hospitalized for AHF, IV infusion of EN 0.5 and 2 mg/kg increased circulating plasma bio-ADM levels and was well-tolerated without treatment-related SAEs occurring during hospitalization and up to 90 days after discharge.
本研究旨在开展一项2期概念验证和安全性研究，以评估在接受标准治疗（SoC）稳定病情后立即给予依尼巴昔单抗（EN）（一种靶向肾上腺髓质素（ADM）N端的非中和性人源化单克隆抗体）对急性心力衰竭（AHF）住院患者的影响。
本前瞻性、开放标签、对照、干预、多中心、剂量递增研究在印度尼西亚的两个心脏病学中心进行。患者被分为两个干预组，在因AHF入院后48小时内，通过1小时静脉输注依次接受0.5mg/kg（SoC + EN 0.5mg/kg，n = 10；第一队列）和2mg/kg（SoC + EN 2mg/kg，n = 10；第二队列）的EN。对照组（n = 10）接受AHF治疗的SoC疗法。所有患者在输注后24小时内持续监测，随后每天监测直至出院。在住院期间及出院后长达90天记录与治疗相关的严重不良事件（SAE）。两种EN剂量均耐受性良好，在住院期间及长达90天的随访中未发现明显的安全问题。每个EN组中10%的患者发生SAE，但被认为与治疗无关。两组之间SAE的发生率无显著差异。发生了5例死亡：对照组3例（30%），而SoC + EN 2mg/kg组有2例死亡（20%）。EN导致输注后24小时内血浆生物活性ADM水平显著升高，SoC + 2mg/kg组升高幅度最大。在静脉输注EN后1小时内，SoC + EN 2mg/kg与0.5mg/kg相比，收缩压、舒张压和平均动脉压显著降低。然而，未导致严重低血压及停药的需要。
在这项针对AHF住院患者的初步安全性研究中，静脉输注0.5mg/kg和2mg/kg的EN可提高循环血浆生物活性ADM水平，耐受性良好，在住院期间及出院后长达90天未发生与治疗相关的SAE。
