ACTION ON COVID-19: A Study to Test Whether BI 764198 Helps Lung Health of People Hospitalised With COVID-19

BI 764198 Efficacy and Safety in Prevention/Progression of ARDS and ARDS-related Complications Secondary to COVID-19 (ACTION ON COVID-19)

This study is open to adults with COVID-19 infection who are in hospital and receive oxygen. Participants need to be 50 years of age or older and need to be at risk of further worsening of their condition.

The purpose of the study is to find out whether a medicine called BI 764198 helps people with COVID-19 infection and breathing problems. BI 764198 may prevent cell death and swelling of the lung tissue and therefore help patients with COVID-19 infection.

Participants are put into 2 groups by chance. One group of participants gets BI 764198 capsules and the other group gets placebo capsules. The placebo capsules look exactly like the BI 764198 capsules but do not contain any medicine. Participants take 1 capsule per day.

Participants are in the study for about a month. At study end, doctors compare the 2 groups for the number of patients that are alive and do not need mechanical breathing support. During the study, the doctors collect information on any health problems of the participants.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: BI 764198

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil, 32380-490
    • Hospital Luxemburgo
  • Campinas, Brazil, 13060-080
    • IPECC - Instituto de Pesquisa Clinica de Campinas
  • Porto Alegre, Brazil, 90160-092
    • Hospital Ernesto Dornelles
  • Santa Catarina, Brazil, 89227
    • Hospital Regional Hans Dieter Schmidt
  • Sao Jose do Rio Preto, Brazil, 15090-000
    • Hospital de Base - Fac Med de Sao Jose do Rio Preto
• Chile
  • Santiago, Chile, 8880465
    • Hospital Padre Alberto Hurtado
  • Valparaiso, Chile, 2341131
    • Hospital Carlos Van Buren
• Mexico
  • Aguascalientes, Mexico, 20230
    • Hospital Cardiologica Aguascalientes
  • Culiacán, Mexico, 80230
    • Hospital General de Culiacán "Dr. Bernardo J. Gastellum"
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
• Puerto Rico
  • Hato Rey, Puerto Rico, 00919
    • Hospital Auxilio Mutuo
  • Rio Piedras, Puerto Rico, 00936
    • Hospital Municipal de San Juan
• Spain
  • A Coruña, Spain, 15006
    • Hospital A Coruña
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Palma de Mallorca, Spain, 07120
    • Hospital Son Espases
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Rapides Regional Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Health St. Vincent Medical Center
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 50 years
• SARS-CoV-2 infection positive confirmed by PCR or approved point-of-care test
• A score of 5 (hospitalised; oxygen by mask or nasal prongs) or 6 (hospitalised; oxygen by non-invasive ventilation or high flow), but not previously ≥7, on the WHO Clinical Progression Scale.
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
• Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must abstain from male female sex or must use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly during hospitalisation for at least 7 days after last trial drug intake

Exclusion Criteria:

• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN).
• Known active infection with HIV or hepatitis B or C.
• Pulmonary oedema/respiratory failure due to cardiogenic insult.
• Previous to hospitalisation, on long-term oxygen therapy.
• A confirmed baseline prolongation of QTc interval to greater than 450 ms in males or 470 ms in females according to the Bazett formula, or any other relevant ECG finding at screening, or concomitant use of medication prolonging QT interval.
• Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR <30 mL/min/1.73 m2).

History of the following cardiac conditions:

• Myocardial infarction within 3 months prior to the first dose
• Unstable angina

• History of clinically significant long QT features on electrocardiogram (ECG) or history of familial long QT

  • Anticipated transfer/discharge to another hospital or care facility other than their place of residence
  • Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo
EXPERIMENTAL: BI 764198 treatment group	Drug: BI 764198; BI 764198

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Alive and Free of Mechanical Ventilation	Percentage of patients alive and free of mechanical ventilation at Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).	At Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Alive and Discharged Free of Oxygen Use	Percentage of patients alive and discharged free of oxygen use is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).	At Day 29
Percentage of Patients With Occurrence of Any Component of Composite: In-hospital Mortality or Intensive Care Unit (ICU) Admission or Mechanical Ventilation	Percentage of patients with occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation is presented. Efficacy endpoint meets when a patient has occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation at Day 29. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).	At Day 29
Time to Clinical Improvement of at Least 2 Points (From Randomisation) on the World Health Organization Clinical Progression Scale, Discharge From the Hospital, or Considered Fit for Discharge	Meets when improvement of at least 2 points on World Health Organization (WHO) Clinical Progression Scale (CPS), discharge from hospital, fit for discharge (score 0, 1, 2, 3 on CPS), whichever comes first. WHO CPS: 0. Uninfected; no viral RNA detected; 1. Asymptomatic; viral RNA detected; 2. Symptomatic; independent; 3. Symptomatic; assistance needed; 4. Hospitalised; no oxygen therapy; 5. Hospitalised; oxygen by mask or nasal prongs; 6. Hospitalised; oxygen by non-invasive ventilation or high flow; 7. Intubation + mechanical ventilation, partial pressure of oxygen/fraction of inspired oxygen (pO2/FiO2) ≥150 or oxygen saturation/FiO2 (SpO2/FiO2) ≥200; 8. Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors; 9. Mechanical ventilation pO2/FiO2 <150 + vasopressors, dialysis, extracorporeal membrane oxygenation (ECMO); 10. Death Only patients with event were analysed. One patient had no creatinine at baseline value, therefore excluded from statistical analysis (N=128).	Up to Day 29
Number of Ventilator Free Days	Number of ventilator free days by Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).	Up to Day 29
Percentage of Mortality at Day 15, 29, 60 and 90	Percentage of mortality is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).	At Day 15, 29, 60 and 90

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 3, 2020
• Primary Completion (ACTUAL): March 24, 2021
• Study Completion (ACTUAL): May 31, 2021

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (ACTUAL): October 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

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: 1434-0009; 2020-003211-96 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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