Study of M5049 in Participants With COVID-19 Pneumonia (ANEMONE)

EMD Serono Research & Development Institute, Inc.149 enrolled

Overview

The study will evaluate the safety and efficacy of orally-administered M5049 in Coronavirus disease 2019 (COVID-19) pneumonia participants who are hospitalized but not on mechanical ventilation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

149

Conditions

Coronavirus Disease 2019

Interventions

M5049DRUG

Participants received M5049 50 milligram (mg) orally twice daily for 14 days.

M5049DRUG

Participants received M5049 100 mg orally twice daily for 14 days.

PlaceboDRUG

Participants received placebo tablets matched to M5049 daily for 14 days.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant provides signed informed consent prior to the initiation of any study assessments * Has laboratory-confirmed SARS-CoV-2 Infection as determined by nucleic acid amplification test, polymerase chain reaction, antigen test or other commercial or public health assay (based on locally acceptable accepted guidelines) in a sample collected less than (\<)10 days prior to randomization * Has chest imaging consistent with COVID-19 pneumonia (as per locally accepted guidelines) If chest imaging is not available during Screening, please discuss with Medical Monitor or designee regarding evidence of probable COVID-19 pneumonia for study participant eligibility * Not on mechanical ventilation or ECMO * Has an SpO2 less than (\<) 94 percent in room air And able to maintain a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) greater than or equal to (\>=) 150 (Or equivalent SpO2/FiO2 \>=190) with a maximum FiO2 0.4 if participant is on chronic low oxygen therapy (less than or equal to 2 Liter), assess their current baseline oxygen requirements for eligibility * Requires hospitalization * Other protocol defined inclusion criteria may apply Exclusion Criteria: * Any condition that could interfere with the study objectives, conduct or evaluation in the opinion of the Investigator or Sponsor or designee * Significantly uncontrolled medical illness (eg, cardiovascular disease, hypertension, diabetes mellitus, obstructive lung disease, neurological associated with seizures (example: cerebrovascular accident/stroke, acute brain infection, traumatic brain injury, progressive brain disease, congenital brain disease or neuropsychiatric disorder) * Known active infection other than COVID-19 * Pregnancy or Breastfeeding * Other protocol defined exclusion criteria may apply

Locations (21)

LAC-USC Medical Center

Los Angeles, California, United States

Sharp Chula Vista Medical Center

Outcomes

Primary Outcomes

Time to Recovery

Time to recovery was defined as the time from first dose (Day 1) to first occurrence of World Health Organization (WHO) 9-point ordinal scale 3 or less. The scoring is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or Extracorporeal membrane oxygenation (ECMO); 8. Death.

Time frame: Day 1 through Day 28

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious TEAEs (SAEs) According to NCI-CTCAE Version 5.0

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs.

Time frame: Day 1 through Day 60

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters

Laboratory investigation included hematology and biochemistry. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.

Time frame: Day 1 through Day 28

Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements

Data from ClinicalTrials.gov

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Secondary Outcomes

Percentage of Participants Alive and Not Requiring Supplemental Oxygenation

The percentage of participants who were alive and did not require supplemental oxygenation or ventilatory support (including noninvasive or mechanical ventilation and Extra Corporeal Membrane Oxygenation \[ECMO\]) reported.

Time frame: Day 3, Day 7, Day 14, Day 21 and Day 28

Number of Participants in Each Clinical Status Category Based on 9-Point Ordinal Scale

Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or ECMO; 8. Death.

Time frame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60

Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours in Room Air

SpO2 is an estimate of the amount of oxygen in the blood. It is the percentage of hemoglobin containing oxygen compared to the total amount of hemoglobin in the blood (that is, oxygenated hemoglobin versus oxygenated and non-oxygenated hemoglobin). SpO2 measured by pulse oximetry. The time to SPO2 greater than or equal to (\>=) 94 percent (%) sustained for at least 24 hours in room air is reported in days.

Time frame: Day 1 through Day 28

Percentage of Participants With All-Cause Mortality

Percentage of Participants who died for any reason reported.

Time frame: Day 1 through Day 60

Time to Intensive Care Unit (ICU) Admission

Time to ICU admission was defined as the time from first dose (Day 1) to the date/time of ICU admission, or death, whichever occurs first, in days. Event-free survival function for time to event (ICU admission or death) estimated via Kaplan-Meier method.

Time frame: Day 1 through Day 28

Time to Non-Invasive Mechanical Ventilation

Time to non-invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status \>= 5, in days. Event-free survival function for time to event (Non-invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death

Time frame: Day 1 through Day 28

Time to Invasive Mechanical Ventilation

Time to invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status \>= 6, in days. Event-free survival function for time to event (invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death.

Time frame: Day 1 through Day 28

Total Length of Stay in Intensive Care Unit (ICU)

Total days in the ICU was defined as the sum, for all ICU admissions, of the time from ICU admission to the date of ICU discharge, in days.

Time frame: Day 1 through Day 60

Total Length of Hospitalization Stay

Total days in the hospital was defined as the sum, for all hospitalization events, of the time from first dose to the date of hospital discharge in days.

Time frame: Day 1 through Day 60

Time to Hospital Discharge

The time to hospital discharge, defined as the time from first dose (Day 1) to the date of first hospitalization discharge, in days.

Time frame: Day 1 through Day 60

Percent Change From Baseline in Inflammatory Biomarkers Over Time

C-Reactive Protein, D-Dimer and Ferritin inflammatory biomarkers were analyzed for this study. Percent Change From Baseline in Inflammatory Biomarkers Over Time were reported here.

Time frame: Baseline, Day 3, Day7, Day 10, Day 14 and Day 28

Percent Change From Baseline in Serum Cytokine Biomarkers

Interleukin 6 and Interleukin 8 serum cytokine biomarkers were analyzed. Percent Change From Baseline in Serum Cytokine Biomarkers were reported.

Time frame: Baseline, Day 3, Day7, Day 14 and Day 28

Percentage of Participants With Relapse

Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.

Time frame: Day 5 through Day 60

Percentage of Participants Who Are Re-Hospitalized

Percentage or participants who are re-hospitalized due to coronavirus disease 2019 (Covid-19) complications were reported.

Time frame: Day 5 through Day 60