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

Coronavirus Disease 2019 Clinical Trial

Official title:

A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia (ANEMONE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04448756
• Other study ID #: MS200569_0026
• Secondary ID: 2020-002248-22
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2020
• Est. completion date: August 16, 2021

Study information

• Verified date: May 2022
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: August 16, 2021
• Est. primary completion date: August 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19
• Pneumonia

Intervention

Drug:
• M5049
Participants received M5049 50 milligram (mg) orally twice daily for 14 days.
• M5049
Participants received M5049 100 mg orally twice daily for 14 days.
• Placebo
Participants received placebo tablets matched to M5049 daily for 14 days.

Locations

Country	Name	City	State
Brazil	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte
Brazil	Hospital Dia do Pulmão	Blumenau
Brazil	Hospital São José - Sociedade Literária e Caritativa Santo Agostinho	Criciúma
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	HMCG - Hospital e Maternidade Dr. Christovão da Gama	Santo André
Brazil	Pesquisare	Santo André
Brazil	Hospital Leforte Morumbi	Sao Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Brazil	Hospital Bandeirantes / Hospital Leforte Liberdade	São Paulo
Brazil	Instituto de Infectologia Emílio Ribas	São Paulo
Philippines	Manila Doctors Hospital	Manila
Philippines	Medical Center Manila - Medicine	Manila
Philippines	Lung Center of the Philippines - Medicine	Quezon
Philippines	Quirino Memorial Medical Center	Quezon
Philippines	Veterans Memorial Medical Center	Quezon
Philippines	East Avenue Medical Center	Quezon City
United States	Christus Spohn Hospital Corpus Christi-Memorial	Corpus Christi	Texas
United States	Henry Ford Medical Center	Detroit	Michigan
United States	LAC-USC Medical Center	Los Angeles	California
United States	Sharp Chula Vista Medical Center	San Diego	California
United States	Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center	Teaneck	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Brazil,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 through Day 28
Primary	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.	Day 1 through Day 60
Primary	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.	Day 1 through Day 28
Primary	Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements	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.	Day 1 through Day 28
Secondary	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.	Day 3, Day 7, Day 14, Day 21 and Day 28
Secondary	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.	Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60
Secondary	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.	Day 1 through Day 28
Secondary	Percentage of Participants With All-Cause Mortality	Percentage of Participants who died for any reason reported.	Day 1 through Day 60
Secondary	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.	Day 1 through Day 28
Secondary	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	Day 1 through Day 28
Secondary	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.	Day 1 through Day 28
Secondary	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.	Day 1 through Day 60
Secondary	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.	Day 1 through Day 60
Secondary	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.	Day 1 through Day 60
Secondary	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.	Baseline, Day 3, Day7, Day 10, Day 14 and Day 28
Secondary	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.	Baseline, Day 3, Day7, Day 14 and Day 28
Secondary	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.	Day 5 through Day 60
Secondary	Percentage of Participants Who Are Re-Hospitalized	Percentage or participants who are re-hospitalized due to coronavirus disease 2019 (Covid-19) complications were reported.	Day 5 through Day 60

External Links

•   Trial Awareness and Transparency website
•   US Medical Information website, Medical Resources