Investigating Otilimab in Patients With Severe Pulmonary COVID-19 Related Disease

NCT ID: NCT04376684

Last Updated: 2024-09-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

1156 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-28

Study Completion Date

2021-08-16

Brief Summary

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OSCAR (Otilimab in Severe COVID-19 Related Disease) is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. The study is being conducted in 2 parts (Part 1 and Part 2). Otilimab is a human monoclonal anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease in Part 1. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of hospitalized participants with severe COVID-19 related pulmonary disease with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to \[\<=\] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

Detailed Description

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Conditions

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Severe Acute Respiratory Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This is a double-blind study.

Study Groups

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Part 1: Participants receiving otilimab

Participants (age \>=18 years and \<=79 years) will receive a single dose of otilimab administered as an IV infusion in addition to standard of care in Part 1.

Group Type EXPERIMENTAL

Otilimab

Intervention Type BIOLOGICAL

Otilimab will be administered once via IV route.

Standard of care

Intervention Type DRUG

All participants will receive standard of care as per institutional protocol.

Part 1: Participants receiving placebo 1

Participants (age \>=18 years and \<=79 years) will receive a single dose of matching placebo administered as an IV infusion in addition to standard of care in Part 1.

Group Type PLACEBO_COMPARATOR

Placebo 1

Intervention Type BIOLOGICAL

Placebo 1 will consist of sterile 0.9 percent (%) sodium chloride solution administered once via IV route.

Standard of care

Intervention Type DRUG

All participants will receive standard of care as per institutional protocol.

Part 2: Participants receiving otilimab

Participants (age 70 years or above) will receive a single dose of otilimab administered as an IV infusion in addition to standard of care in Part 2.

Group Type EXPERIMENTAL

Otilimab

Intervention Type BIOLOGICAL

Otilimab will be administered once via IV route.

Standard of care

Intervention Type DRUG

All participants will receive standard of care as per institutional protocol.

Part 2: Participants receiving placebo 2

Participants (age 70 years or above) will receive a single dose of matching placebo administered as an IV infusion in addition to standard of care in Part 2.

Group Type PLACEBO_COMPARATOR

Placebo 2

Intervention Type BIOLOGICAL

Placebo 2 will consist of sterile 5% dextrose or 5% glucose solution administered once via IV route.

Standard of care

Intervention Type DRUG

All participants will receive standard of care as per institutional protocol.

Interventions

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Otilimab

Otilimab will be administered once via IV route.

Intervention Type BIOLOGICAL

Placebo 1

Placebo 1 will consist of sterile 0.9 percent (%) sodium chloride solution administered once via IV route.

Intervention Type BIOLOGICAL

Placebo 2

Placebo 2 will consist of sterile 5% dextrose or 5% glucose solution administered once via IV route.

Intervention Type BIOLOGICAL

Standard of care

All participants will receive standard of care as per institutional protocol.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participants aged \>=18 years and \<=79 years at the time of obtaining informed consent.
* Participants must:

1. have positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) result (any validated test, for example. reverse transcription polymerase chain reaction \[RT-PCR\] \[performed on an appropriate specimen; for example: respiratory tract sample\])
2. and be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography \[CT\] scan consistent with COVID-19)
3. and be developing new onset of oxygenation impairment requiring any of the following:

1. high-flow oxygen (\>=15L/min)
2. non-invasive ventilation (for example. CPAP, BIPAP)
3. mechanical ventilation \<=48 hours prior to dose
4. and have increased biological markers of systemic inflammation (either C-reactive protein \[CRP\] \>upper limit of normal \[ULN\] or serum ferritin \>ULN).
* No gender restriction.
* Female participants must meet and agree to abide by the contraceptive criteria detailed in the protocol. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* A female participant is eligible to participate if she is not pregnant or breastfeeding or if she is using highly effective contraceptive methods. Women of non-childbearing potential can also participate. A negative highly sensitive pregnancy test at hospital admission or before the first dose of study intervention.
* Capable of giving written informed consent.


* Participants aged 70 years or above at the time of obtaining informed consent.
* Participants must:

1. have positive SARS-CoV-2 result (any validated test, for example. RT-PCR \[performed on an appropriate specimen; for example. respiratory tract sample\])
2. and be hospitalized due to diagnosis of pneumonia (chest X-ray or CT scan consistent with COVID-19).
3. and be developing new onset of oxygenation impairment requiring any of the following:

1. high-flow oxygen (\>=15L/min)
2. non-invasive ventilation (for example. CPAP, BiPAP)
3. mechanical ventilation \<=48 hours prior to dose
4. and have increased biological markers of systemic inflammation (either CRP \>ULN or serum ferritin \>ULN.
* No gender restriction.
* Capable of giving written informed consent.

Exclusion Criteria

* Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
* Multiple organ failure according to the investigator's judgement or a Sequential Organ Failure assessment (SOFA score) \>10 if in the ICU.
* Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis or high-dose (\>0.15 micrograms \[mcg\]/kilograms \[kg\]/min) noradrenaline (or equivalent) or more than one vasopressor.
* Current serious or uncontrolled medical condition (for example: significant pulmonary disease \[such as severe chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis\], heart failure \[New York Heart Association {NYHA} class III or higher\], renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months) or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
* Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-CoV-2).
* Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
* Known Human Immunodeficiency Virus (HIV) regardless of immunological status.
* Known hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (HCV) positive.
* Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy.
* Received monoclonal antibody therapy (for examplee. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin, or planned to be received, during the study.
* Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, Janus Kinase (JAK) inhibitors (for examplee. baricitinib, tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned to be received during the study.
* History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy.
* Received COVID-19 convalescent plasma within 48 hours of randomization.
* Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 milligrams (mg) or equivalent per day.
* Treatment with an investigational drug within 30 days of randomization.
* Participating in other drug clinical trials, including for COVID-19.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 times ULN.
* Platelets \<50,000/cubic millimeters (mm\^3)
* Hemoglobin \<=9 grams per deciliter (g/dL)
* Absolute neutrophil count (ANC) \<1.5 times 10\^9/L (neutropenia \>= Grade 2)
* Estimated glomerular filtration rate (GFR) \<=30 milliliters (mL)/min/1.73 meter square (/m\^2).
* Pregnant or breastfeeding females.


* Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
* Multiple organ failure according to the investigator's judgement or a SOFA score \>10 if intubated in the ICU.
* ECMO hemofiltration/dialysis, or more than one inotrope/vasopressor of any class.
* Current serious or uncontrolled medical condition (for example. significant pulmonary disease \[such as severe COPD or pulmonary fibrosis\], heart failure \[NYHA class III or higher\], severe renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months), severe dementia, severe disability, or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
* Untreated systemic bacterial, fungal, viral, or other infection (other than SARSCoV-2).
* Known active TB, history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
* Known HIV regardless of immunological status.
* Known HBsAg and/or anti-HCV positive (participants demonstrating a sustained virologic response (SVR) are not excluded from participation).
* Currently receiving radiotherapy, chemotherapy (hormone based therapies are permitted) or immunotherapy for malignancy.
* Received monoclonal antibody therapy (for example. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin, or planned to be received during the study.
* Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors (for example. baricitinib, tofacitinib, upadacitinib), nintedanib, disease modifying antirheumatic drugs (DMARDs) (for example. methotrexate) within the last 3 months prior to randomization or planned to be received during the study.
* History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy.
* Received COVID-19 convalescent plasma within 48 hours of randomization.
* Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition at a dose higher than prednisone 10 mg or equivalent per day.
* Treatment with an investigational drug or substance within 30 days of randomization unless approved by the Medical Monitor.
* Participating in other drug clinical trials, including for COVID-19.
* AST or ALT \>5 times ULN.
* Platelets \<50,000/mm\^3.
* Hemoglobin \<=9 g/dL
* ANC \<1.0 x 10\^9/L (neutropenia \>= Grade 3).
* Estimated GFR \<=30 mL/min/1.73 m\^2.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Mobile, Alabama, United States

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Little Rock, Arkansas, United States

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Sacramento, California, United States

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Torrance, California, United States

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Gainesville, Florida, United States

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Winfield, Illinois, United States

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Baltimore, Maryland, United States

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Germantown, Maryland, United States

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Silver Spring, Maryland, United States

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Saint Louis Park, Minnesota, United States

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Saint Paul, Minnesota, United States

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Jackson, Mississippi, United States

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Reno, Nevada, United States

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Buffalo, New York, United States

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Charlotte, North Carolina, United States

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Toledo, Ohio, United States

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Doylestown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Roanoke, Virginia, United States

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Tacoma, Washington, United States

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Milwaukee, Wisconsin, United States

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Munro, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Brussels, , Belgium

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Yvoir, , Belgium

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Belo Horizonte, Minas Gerais, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Vancouver, British Columbia, Canada

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Ottawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Saint-Jérôme, Quebec, Canada

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Santiago, , Chile

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Santiago, , Chile

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Bogotá, , Colombia

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Amiens, , France

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Angers, , France

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Argenteuil, , France

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La Roche-sur-Yon, , France

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La Tronche, , France

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Limoges, , France

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Melun, , France

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Paris, , France

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Pierre-Bénite, , France

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Strasbourg, , France

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Strasbourg, , France

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Valenciennes, , France

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Aurangabad, , India

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Aurangabad, , India

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Hyderabad, , India

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Kolkata, , India

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Kolkata, , India

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Mumbai, , India

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Nagpur, , India

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New Delhi, , India

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Pune, , India

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Pune, , India

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Napoli, Campania, Italy

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Aichi, , Japan

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Kanagawa, , Japan

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Kanagawa, , Japan

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Osaka, , Japan

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Saitama, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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México, , Mexico

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's-Hertogenbosch, , Netherlands

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Breda, , Netherlands

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Enschede, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Bydgoszcz, , Poland

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Krakow, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Barnaul, , Russia

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Chelyabinsk, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Omsk, , Russia

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Perm, , Russia

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Saint Petersburg, , Russia

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Ufa, , Russia

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Voronezh, , Russia

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Yekaterinburg, , Russia

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Benoni, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Panorama, , South Africa

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Tygerberg, , South Africa

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Worcester, , South Africa

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Logroño, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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San Sebastián de Los Reyes/Madrid, , Spain

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Manchester, Greater Manchester, United Kingdom

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Newcastle, Northumberland, United Kingdom

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Liverpool, , United Kingdom

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Countries

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United States Argentina Belgium Brazil Canada Chile Colombia France India Italy Japan Mexico Netherlands Peru Poland Russia South Africa Spain United Kingdom

References

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Patel J, Bass D, Beishuizen A, Bocca Ruiz X, Boughanmi H, Cahn A, Colombo H, Criner GJ, Davy K, de-Miguel-Diez J, Doreski PA, Fernandes S, Francois B, Gupta A, Hanrott K, Hatlen T, Inman D, Isaacs JD, Jarvis E, Kostina N, Kropotina T, Lacherade JC, Lakshminarayanan D, Martinez-Ayala P, McEvoy C, Meziani F, Monchi M, Mukherjee S, Munoz-Bermudez R, Neisen J, O'Shea C, Plantefeve G, Schifano L, Schwab LE, Shahid Z, Shirano M, Smith JE, Sprinz E, Summers C, Terzi N, Tidswell MA, Trefilova Y, Williamson R, Wyncoll D, Layton M. A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR). Eur Respir J. 2023 Feb 2;61(2):2101870. doi: 10.1183/13993003.01870-2021. Print 2023 Feb.

Reference Type BACKGROUND
PMID: 36229048 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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214094

Identifier Type: -

Identifier Source: org_study_id

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