Clinical trial NCT04448756: Study of M5049 in Participants With COVID-19 Pneumonia (ANEMONE)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Disease 2019
Keywords: COVID-19
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2020-06-26
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Recovery
timeFrame: Day 1 through Day 28
measure: 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
timeFrame: Day 1 through Day 60
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
timeFrame: Day 1 through Day 28
measure: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements
timeFrame: Day 1 through Day 28
Secondary outcomes:
measure: Percentage of Participants Alive and Not Requiring Supplemental Oxygenation
timeFrame: Day 3, Day 7, Day 14, Day 21 and Day 28
measure: Number of Participants in Each Clinical Status Category Based on 9-Point Ordinal Scale
timeFrame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60
measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours in Room Air
timeFrame: Day 1 through Day 28
measure: Percentage of Participants With All-Cause Mortality
timeFrame: Day 1 through Day 60
measure: Time to Intensive Care Unit (ICU) Admission
timeFrame: Day 1 through Day 28
measure: Time to Non-Invasive Mechanical Ventilation
timeFrame: Day 1 through Day 28
measure: Time to Invasive Mechanical Ventilation
timeFrame: Day 1 through Day 28
measure: Total Length of Stay in Intensive Care Unit (ICU)
timeFrame: Day 1 through Day 60
measure: Total Length of Hospitalization Stay
timeFrame: Day 1 through Day 60
measure: Time to Hospital Discharge
timeFrame: Day 1 through Day 60
measure: Percent Change From Baseline in Inflammatory Biomarkers Over Time
timeFrame: Baseline, Day 3, Day7, Day 10, Day 14 and Day 28
measure: Percent Change From Baseline in Serum Cytokine Biomarkers
timeFrame: Baseline, Day 3, Day7, Day 14 and Day 28
measure: Percentage of Participants With Relapse
timeFrame: Day 5 through Day 60
measure: Percentage of Participants Who Are Re-Hospitalized
timeFrame: Day 5 through Day 60
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC-USC Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Chula Vista Medical Center
state: California
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Teaneck
country: United States
facility: Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center
state: New Jersey
city: Corpus Christi
country: United States
facility: Christus Spohn Hospital Corpus Christi-Memorial
state: Texas
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte
city: Blumenau
country: Brazil
facility: Hospital Dia do Pulmão
city: Criciúma
country: Brazil
facility: Hospital São José - Sociedade Literária e Caritativa Santo Agostinho
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Santo André
country: Brazil
facility: HMCG - Hospital e Maternidade Dr. Christovão da Gama
city: Santo André
country: Brazil
facility: Pesquisare
city: Sao Paulo
country: Brazil
facility: Hospital Leforte Morumbi
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
city: São Paulo
country: Brazil
facility: Hospital Bandeirantes / Hospital Leforte Liberdade
city: São Paulo
country: Brazil
facility: Instituto de Infectologia Emílio Ribas
city: Manila
country: Philippines
facility: Manila Doctors Hospital
city: Manila
country: Philippines
facility: Medical Center Manila - Medicine
city: Quezon City
country: Philippines
facility: East Avenue Medical Center
city: Quezon
country: Philippines
facility: Lung Center of the Philippines - Medicine
city: Quezon
country: Philippines
facility: Quirino Memorial Medical Center
city: Quezon
country: Philippines
facility: Veterans Memorial Medical Center
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: 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.