Asunercept in Patients With Severe COVID-19

Study Overview
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Brief Summary
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This is an open-label, randomized, phase II study with the main objective to investigate the effectiveness and safety of an investigational drug (APG101; International Nonproprietary Name: asunercept) in patients with severe COVID-19 disease. The study aims to decrease overall and SARS-CoV-2 associated pneumonia mortality in patients with COVID-19 as well as to decrease the percentage of patients admitted to Intensive Care Unit (ICU), decrease the need to supply oxygen to patients, reduce the number of days patients are hospitalized in ICU and/or on the ward, decrease the number of days required to obtain a negative result in the PCR (Polymerase Chain Reaction, a laboratory technique that allows the amplification of small fragments of DNA to detect the presence of the virus) test for COVID-19 and decrease the levels of markers that indicate pneumonia.

Official Title
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A Multicenter, Randomised, Controlled, Open Label Trial on the Efficacy and Safety of Asunercept for Patients With Severe COVID-19 Disease

Conditions
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COVID-19 Induced Pneumonia, Covid19

Intervention / Treatment
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* Biological: Asunercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory confirmed infection with SARS-CoV-2 OR typical radiological signs of SARS-CoV-2 infection Hospitalisation due to COVID-19 Informed Consent obtained, the patient understands and agrees to comply with the planned study procedures. If a potential patient is unconscious, the Patient Information Sheet with the Informed Consent Form can be signed by the legal representative, if he/she accompanies the patient. It can be signed by a Concilium consisting of doctors (2), investigator and an independent witness in case the legal representative is not available. ≥18 years of age Willingness to perform effective measures of contraception during the study. Signs of respiratory deterioration such as oxygen saturation ≤94% when breathing ambient air or >3% drop in oxygen saturation in case of chronic obstructive lung disease OR need for oxygen supplementation to achieve satisfactory blood oxygen saturation (sPO2>90% at room air) as well as the need for non-invasive ventilation, high-flow oxygen devices or mechanical ventilation or radiological or clinical signs of pneumonia. Exclusion Criteria: Moribund, or estimated life expectancy <1 month (e.g., terminal cancer, etc.) Patient does not qualify for intensive care, based on local triage criteria Pregnancy or breast feeding Severe liver dysfunction (e.g. ALT/AST > 5 times upper limit of normal) Anticipated discharge from hospital within 48 hours Other potent anti-inflammatory treatment, e.g. TNF- blocking therapies Mechanical ventilation for >48 hours Known active HIV or viral hepatitis infection Known active tuberculosis Known hereditary fructose intolerance

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Asunercept/APG101 will be tested in three parallel intervention arms and compared with Standard of Care (SoC). The study will compare treatment efficacy of SoC to that of weekly intravenous infusions of Asunercept at three different doses. Patients will be randomised into four groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br> | |
| Experimental: Standard of Care + Asunercept 25 mg<br> | Biological: Asunercept<br>* Asunercept (APG101) will be administered once per week as an i.v. infusion<br>|
| Experimental: Standard of Care + Asunercept 100 mg<br> | Biological: Asunercept<br>* Asunercept (APG101) will be administered once per week as an i.v. infusion<br>|
| Experimental: Standard of Care + Asunercept 400 mg<br> | Biological: Asunercept<br>* Asunercept (APG101) will be administered once per week as an i.v. infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to sustained improvement of one category (i.e. two consecutive days) from randomisation | The primary endpoint is time to clinical improvement which is defined as time from randomisation to an (sustained) improvement of at least one category on two consecutive days compared to the status at randomisation measured on a nine-category ordinal scale (proposed by WHO). | Day 1-29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy according to the National Early Warning Score (NEWS) | Time to discharge or to a NEWS of ≤2 and maintained for 24 hours, whichever occurs first Change from baseline | Day 1-29 | 
| Oxygenation | Oxygenation free days until day 29 Incidence and duration of new oxygen use during the trial | Day 1-29 | 
| Ventilation | Ventilator free days until day 29 Incidence and duration fo new mechanical ventilation use during the trial | Day 1-29 | 
| Hospitalisation - Length | Duration of hospitalisation Length of ICU stay (in days) | Day 1-29 | 
| Hospitalisation - Proportion on ICU | Proportion of patients admitted to ICU | Day 1-29 | 
| Mortality | 15-day, 29-day, 60-day and 90-day all-cause mortality | Up to 90 days |