Multicenter, Randomized, Double-blind, Biomarker-guided, Phase II Trial With Adrecizumab (HAM 8101) to Improve proGNosis and outcomES in Patients With Moderate to Severe COVID-19

AGNES-19

The clinical trial is designed as a prospective, multi-center, double-blind, randomised, placebo-controlled, interventional trial to assess safety, tolerability and efficacy of Adrecizumab (on top of SOC) in patients with COVID-19, and to evaluate if improvement of vascular integrity with Adrecizumab on top of SOC is superior to placebo/ control substance (NaCl 0.9%) on top of SOC in reduction of morbidity and mortality endpoints in patients with COVID-19. The main reason for admission to ICU and need for mechanical ventilation of these patients is acute lung injury within a broad pneumonic spectrum, increased ventricular filling pressures and resulting congestion. It is hypothesized, that Adrenomedullin (ADM) is a key player in the (dys)-regulation of vascular integrity (Figure 2). Adrecizumab is the first-in-class humanized monoclonal anti-Adrenomedullin antibody, and acts as a long-lasting plasma Adrenomedullin enhancer stabilizing barrier function at a reasonable safety profile. The mode of action for the anti-Adrenomedullin antibody Adrecizumab has been developed on the basis of published data, own experimental data and theoretical considerations.

2022-10-06

2023-08-25

2023-11-15

Terminated

Early phase I

16

Inclusion Criteria: * Hospitalization with moderate to severe COVID-19, defined as fulfilling at a minimum the following clinical status category on the WHO 8-point ordinal scale: (i) "score 4" \[oxygen via mask or nasal\] * Laboratory-confirmed SARS-CoV-2 infection at index hospitalisation as determined by PCR or other validated commercial or public health assay * Bio-ADM ≥50 pg/mL or ≥30% increase until the end of the next day (with a minimum of 35 pg/mL at all) * DPP3 ≤30 ng/mL * Age ≥18 years at time of screening * Body weight ≤ 150 kg at time of screening Exclusion Criteria: * Life expectancy less than 3 months before COVID-19 at the discretion of the Investigator * Invasive mechanical ventilation ≥ 72 hours at time-point of randomization * Resuscitation \> 45 minutes * Hypersensitivity to the active substance, to Adrecizumab or any of its excipients, or known serious hypersensitivity to other monoclonal antibodies * Uncontrolled haematological/ oncological malignancies * Pre-existing severe chronic liver disease (i.e. Child-Pugh C) before COVID-19 hospitalization * Absolute neutropenia \<500 per μL

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2024-01-03