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

NCT04448756 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MS200569_00262020-002248-22
• Study Type: interventional
• Target: 149
• Locations: 3 countries
• Sites: 21

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.

Conditions

Coronavirus Disease 2019

Keywords

COVID-19; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (14)

• Percentage of Participants Alive and Not Requiring Supplemental Oxygenation

  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

  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

  Day 1 through Day 28

• Percentage of Participants With All-Cause Mortality

  Day 1 through Day 60

• Time to Intensive Care Unit (ICU) Admission

  Day 1 through Day 28

Study Arms (3)

M5049 50 mg

EXPERIMENTAL

Drug: M5049

M5049 100 mg

EXPERIMENTAL

Drug: M5049

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

M5049 DRUG

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

M5049 50 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (21)

LAC-USC Medical Center

Los Angeles, California, 90033, United States

Location

Sharp Chula Vista Medical Center

San Diego, California, 92123, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48202, United States

Location

Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center

Teaneck, New Jersey, 07666, United States

Location

Christus Spohn Hospital Corpus Christi-Memorial

Corpus Christi, Texas, 78404, United States

Location

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Brazil

Location

Hospital Dia do Pulmão

Blumenau, Brazil

Location

Hospital São José - Sociedade Literária e Caritativa Santo Agostinho

Criciúma, Brazil

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

HMCG - Hospital e Maternidade Dr. Christovão da Gama

Santo André, Brazil

Location

Pesquisare

Santo André, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, Brazil

Location

Hospital Bandeirantes / Hospital Leforte Liberdade

São Paulo, Brazil

Location

Hospital Leforte Morumbi

São Paulo, Brazil

Location

Instituto de Infectologia Emílio Ribas

São Paulo, Brazil

Location

Manila Doctors Hospital

Manila, Philippines

Location

Medical Center Manila - Medicine

Manila, Philippines

Location

Lung Center of the Philippines - Medicine

Quezon, Philippines

Location

Quirino Memorial Medical Center

Quezon, Philippines

Location

Veterans Memorial Medical Center

Quezon, Philippines

Location

East Avenue Medical Center

Quezon City, Philippines

Location

Related Publications (2)

• McKinnon JE, Santiaguel J, Murta de Oliveira C, Yu D, Khursheed M, Moreau F, Klopp-Schulze L, Shaw J, Roy S, Kao AH; ANEMONE Study Team. Enpatoran in COVID-19 pneumonia: Safety and efficacy results from a phase II randomized trial. Clin Transl Sci. 2023 Dec;16(12):2640-2653. doi: 10.1111/cts.13658. Epub 2023 Oct 23.

  PMID: 37873555 DERIVED

• 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.

  PMID: 35390178 DERIVED

Related Links

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

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: June 26, 2020
• Study Start: July 29, 2020
• Primary Completion: August 16, 2021
• Study Completion: August 16, 2021
• Last Updated: June 6, 2022
• Results First Posted: June 6, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• 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
• 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.

Locations

BR (10); PH (6); US (5)