Asunercept in Patients With Severe COVID-19 (ASUNCTIS)

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; COVID-19 Induced Pneumonia
• Intervention / Treatment: Biological: Asunercept

• Study Type: Interventional
• Enrollment (Actual): 438
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation
    • Republican Clinical Infectious Hospital n.a. professor A.F. Agafonov
  • Kemerovo, Russian Federation
    • Scientific Research lnstitute fоr Соmрlех lssues of Cardiovascular Diseases
  • Krasnodar, Russian Federation
    • Federal State Budgetary Educational Institution of Higher Education "Kuban State Medical University" of the Ministry of Health of the Russian Federation
  • Krasnodar, Russian Federation
    • State Budgetary Healthcare Institution "Scientific Research Institute - Regional clinical hospital No. 1 n.a. professor S.V. Ochapovsky" of the Ministry of Healthcare of Krasnodar Krai
  • Nizhny Novgorod, Russian Federation
    • State Budgetary Institution of Health of the Nizhny Novgorod Region "Infectious Clinical Hospital No. 2 of Nizhny Novgorod"
  • Ryazan, Russian Federation
    • Ryazan State Medical University n.a. academician I.P. Pavlov
  • Saint Petersburg, Russian Federation
    • Saint Petersburg state budgetary healthcare institution "City hospital of Saint George the great Martyr"
• Spain
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • San Sebastián De Los Reyes, Spain
    • Hospital Universitario Infanta Sofía
  • Zaragoza, Spain
    • Hospital Clinico Universitario Lozano Blesa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Apogenix AG
• Investigators: Principal Investigator: Pilar Ruiz-Seco, PhD-MD, Hospital Universitario Infanta Sofía, Madrid

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2020
• Primary Completion (Actual): October 29, 2021
• Study Completion (Actual): December 21, 2021

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: APG101_CD_017; 2020-001887-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No