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

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)

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 Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019
• Intervention / Treatment: Drug: M5049; Drug: M5049; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Santa Casa de Misericordia de Belo Horizonte
  • Blumenau, Brazil
    • Hospital Dia do Pulmao
  • Criciúma, Brazil
    • Hospital São José - Sociedade Literária e Caritativa Santo Agostinho
  • Porto Alegre, Brazil
    • Hospital de Clinicas de Porto Alegre
  • Santo André, Brazil
    • HMCG - Hospital e Maternidade Dr. Christovão da Gama
  • Santo André, Brazil
    • Pesquisare
  • Sao Paulo, Brazil
    • Hospital Leforte Morumbi
  • São Paulo, Brazil
    • Hospital Alemao Oswaldo Cruz
  • São Paulo, Brazil
    • Instituto de Infectologia Emilio Ribas
  • São Paulo, Brazil
    • Hospital Bandeirantes / Hospital Leforte Liberdade
• Philippines
  • Manila, Philippines
    • Manila Doctors Hospital
  • Manila, Philippines
    • Medical Center Manila - Medicine
  • Quezon, Philippines
    • Lung Center of the Philippines - Medicine
  • Quezon, Philippines
    • Quirino Memorial Medical Center
  • Quezon, Philippines
    • Veterans Memorial Medical Center
  • Quezon City, Philippines
    • East Avenue Medical Center
• United States
  • California
    • Los Angeles, California, United States, 90033
      • LAC-USC Medical Center
    • San Diego, California, United States, 92123
      • Sharp Chula Vista Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Christus Spohn Hospital Corpus Christi-Memorial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Participants received placebo tablets matched to M5049 daily for 14 days.
EXPERIMENTAL: M5049 50 mg	Drug: M5049; Participants received M5049 50 milligram (mg) orally twice daily for 14 days.; Drug: M5049; Participants received M5049 100 mg orally twice daily for 14 days.
EXPERIMENTAL: M5049 100 mg	Drug: M5049; Participants received M5049 50 milligram (mg) orally twice daily for 14 days.; Drug: M5049; Participants received M5049 100 mg orally twice daily for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Percentage of Participants With All-Cause Mortality	Percentage of Participants who died for any reason reported.	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.	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	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.	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.	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.	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.	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.	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.	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.	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.	Day 5 through Day 60

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Klopp-Schulze L, Shaw JV, Dong JQ, Khandelwal A, Vazquez-Mateo C, Goteti K. Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. Clin Pharmacol Ther. 2022 Aug;112(2):297-306. doi: 10.1002/cpt.2606. Epub 2022 May 21.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 29, 2020
• Primary Completion (ACTUAL): August 16, 2021
• Study Completion (ACTUAL): August 16, 2021

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (ACTUAL): June 26, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia
• Other Study ID Numbers: MS200569_0026; 2020-002248-22 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; 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