Study of M5049 in Participants With COVID-19 Pneumonia (ANEMONE)
- Registration Number
- NCT04448756
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 149
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description M5049 50 mg M5049 - M5049 100 mg M5049 - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Time to Recovery Day 1 through Day 28 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.
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 Day 1 through Day 60 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.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters Day 1 through Day 28 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.
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements Day 1 through Day 28 12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
- Secondary Outcome Measures
Name Time Method Time to Intensive Care Unit (ICU) Admission Day 1 through Day 28 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 to Non-Invasive Mechanical Ventilation Day 1 through Day 28 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 to Invasive Mechanical Ventilation Day 1 through Day 28 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.
Total Length of Stay in Intensive Care Unit (ICU) Day 1 through Day 60 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.
Percentage of Participants Alive and Not Requiring Supplemental Oxygenation Day 3, Day 7, Day 14, Day 21 and Day 28 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.
Number of Participants in Each Clinical Status Category Based on 9-Point Ordinal Scale Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60 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 to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours in Room Air Day 1 through Day 28 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.
Percentage of Participants With All-Cause Mortality Day 1 through Day 60 Percentage of Participants who died for any reason reported.
Total Length of Hospitalization Stay Day 1 through Day 60 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 to Hospital Discharge Day 1 through Day 60 The time to hospital discharge, defined as the time from first dose (Day 1) to the date of first hospitalization discharge, in days.
Percent Change From Baseline in Inflammatory Biomarkers Over Time Baseline, Day 3, Day7, Day 10, Day 14 and Day 28 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.
Percent Change From Baseline in Serum Cytokine Biomarkers Baseline, Day 3, Day7, Day 14 and Day 28 Interleukin 6 and Interleukin 8 serum cytokine biomarkers were analyzed. Percent Change From Baseline in Serum Cytokine Biomarkers were reported.
Percentage of Participants With Relapse Day 5 through Day 60 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.
Percentage of Participants Who Are Re-Hospitalized Day 5 through Day 60 Percentage or participants who are re-hospitalized due to coronavirus disease 2019 (Covid-19) complications were reported.
Trial Locations
- Locations (21)
Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center
🇺🇸Teaneck, New Jersey, United States
Hospital Dia do Pulmão
🇧🇷Blumenau, Brazil
Instituto de Infectologia EmÃlio Ribas
🇧🇷São Paulo, Brazil
Manila Doctors Hospital
🇵ðŸ‡Manila, Philippines
East Avenue Medical Center
🇵ðŸ‡Quezon City, Philippines
Lung Center of the Philippines - Medicine
🇵ðŸ‡Quezon, Philippines
Pesquisare
🇧🇷Santo André, Brazil
Hospital de ClÃnicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
HMCG - Hospital e Maternidade Dr. Christovão da Gama
🇧🇷Santo André, Brazil
Santa Casa de Misericórdia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Hospital Leforte Morumbi
🇧🇷Sao Paulo, Brazil
Medical Center Manila - Medicine
🇵ðŸ‡Manila, Philippines
Quirino Memorial Medical Center
🇵ðŸ‡Quezon, Philippines
Veterans Memorial Medical Center
🇵ðŸ‡Quezon, Philippines
Hospital São José - Sociedade Literária e Caritativa Santo Agostinho
🇧🇷Criciúma, Brazil
LAC-USC Medical Center
🇺🇸Los Angeles, California, United States
Sharp Chula Vista Medical Center
🇺🇸San Diego, California, United States
Henry Ford Medical Center
🇺🇸Detroit, Michigan, United States
Christus Spohn Hospital Corpus Christi-Memorial
🇺🇸Corpus Christi, Texas, United States
Hospital Alemão Oswaldo Cruz
🇧🇷São Paulo, Brazil
Hospital Bandeirantes / Hospital Leforte Liberdade
🇧🇷São Paulo, Brazil