Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients — the randomized, EU-wide, placebo-controlled, phase II study design of IXION

Abstract

Background More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. Methods IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4–6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. Discussion With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for. Trial registration EudraCT 2021-005059-35. Registered on 12 December 2021. Study Code TMP-2204-2021-47.

Artificial intelligence research in the COVend COVID-19 clinical trial project

“…According to the published study protocol [4], 306 hospitalised patients will be included to the placebo-controlled, double-blinded, parallel, randomized (2:1), phase II clinical study of the FX06 drug.…”

“…The inclusion and exclusion criteria of the study patients exclude those COVID-19 patients who have serious and/or uncontrolled diseases with a bad prognosis that are likely to interfere with the evaluation of the patient's safety and with the study outcome [4]. The main objective is to compare the progression/worsening disease state of the patients in the intervention and control groups of the patients at the end of the 28-day study period.…”

“…Many variables are measured from the subjects during the study. These are also related to the secondary objectives such as overall disease progression, lung function, systemic inflammation, survival, capillary refill time, duration hospital stay, and drug accountability [4]. In addition to the traditional measurements of vital signs and the information in the patient data management systems, OMICS analysis of the samples from the subjects is also to be performed.…”

Microvascular Leakage as Therapeutic Target for Ischemia and Reperfusion Injury

“…Since the loss of endothelial barrier function has pathophysiological relevance in many diseases, FX06 has shown anecdotal beneficial effects in patients with Ebola infection [177] and COVID-19-induced respiratory distress syndrome [178]. This latter application is now under systematic investigation in the prospective randomized IXION trial [179].…”