Asunercept in Patients With Severe COVID-19 (ASUNCTIS)

• ClinicalTrials.gov Identifier: NCT04535674
• Recruitment Status: Completed
• First Posted: September 2, 2020
• Last Update Posted: January 14, 2022
• Sponsor: Apogenix AG
• Information provided by (Responsible Party): Apogenix AG

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19 Induced Pneumonia; Covid19	Biological: Asunercept	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 438 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomised, Controlled, Open Label Trial on the Efficacy and Safety of Asunercept for Patients With Severe COVID-19 Disease
• Actual Study Start Date: October 9, 2020
• Actual Primary Completion Date: October 29, 2021
• Actual Study Completion Date: December 21, 2021

Arms and Interventions

Arm	Intervention/treatment
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 100 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

Outcome Measures

Primary Outcome Measures :

1. Time to sustained improvement of one category (i.e. two consecutive days) from randomisation [ Time Frame: Day 1-29 ]
   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).

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Russian Federation

Republican Clinical Infectious Hospital n.a. professor A.F. Agafonov

Kazan, Russian Federation

Scientific Research lnstitute fоr Соmрlех lssues of Cardiovascular Diseases

Kemerovo, 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

Krasnodar, Russian Federation

State Budgetary Institution of Health of the Nizhny Novgorod Region "Infectious Clinical Hospital No. 2 of Nizhny Novgorod"

Nizhny Novgorod, Russian Federation

Ryazan State Medical University n.a. academician I.P. Pavlov

Ryazan, Russian Federation

Saint Petersburg state budgetary healthcare institution "City hospital of Saint George the great Martyr"

Saint Petersburg, Russian Federation

Spain

Hospital Universitario Infanta Leonor

Madrid, Spain

Hospital Universitario La Paz

Madrid, Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Spain

Hospital Universitario Infanta Sofia

San Sebastián De Los Reyes, Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Sponsors and Collaborators

Apogenix AG

Investigators

• Principal Investigator: Pilar Ruiz-Seco, PhD-MD; Hospital Universitario Infanta Sofía, Madrid

More Information

• Responsible Party: Apogenix AG
• ClinicalTrials.gov Identifier: NCT04535674
• Other Study ID Numbers: APG101_CD_017; 2020-001887-27 ( EudraCT Number )
• First Posted: September 2, 2020
• Last Update Posted: January 14, 2022
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases