Official Title
A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease
Brief Summary

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 [

Completed
Severe Acute Respiratory Syndrome

Biological: Otilimab

Otilimab will be administered once via IV route.

Biological: Placebo 1

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

Biological: Placebo 2

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

Drug: Standard of care

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

Eligibility Criteria

Inclusion criteria for Part 1:

- 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.

Inclusion Criteria for Part 2:

- 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 for Part 1:

- 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.

Exclusion Criteria for Part 2:

- 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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Argentina
Belgium
Brazil
Canada
Chile
Colombia
France
India
Italy
Japan
Mexico
Netherlands
Peru
Poland
Russian Federation
South Africa
Spain
United Kingdom
United States
Locations

GSK Investigational Site
Mobile, Alabama, United States

GSK Investigational Site
Little Rock, Arkansas, United States

GSK Investigational Site
Sacramento, California, United States

GSK Investigational Site
Torrance, California, United States

GSK Investigational Site
Gainesville, Florida, United States

GSK Investigational Site
Winfield, Illinois, United States

GSK Investigational Site
Baltimore, Maryland, United States

GSK Investigational Site
Germantown, Maryland, United States

GSK Investigational Site
Silver Spring, Maryland, United States

GSK Investigational Site
Saint Louis Park, Minnesota, United States

GSK Investigational Site
Saint Paul, Minnesota, United States

GSK Investigational Site
Jackson, Mississippi, United States

GSK Investigational Site
Reno, Nevada, United States

GSK Investigational Site
Buffalo, New York, United States

GSK Investigational Site
Charlotte, North Carolina, United States

GSK Investigational Site
Toledo, Ohio, United States

GSK Investigational Site
Doylestown, Pennsylvania, United States

GSK Investigational Site
Philadelphia, Pennsylvania, United States

GSK Investigational Site
Roanoke, Virginia, United States

GSK Investigational Site
Tacoma, Washington, United States

GSK Investigational Site
Milwaukee, Wisconsin, United States

GSK Investigational Site
Munro, Buenos Aires, Argentina

GSK Investigational Site
Cordoba, Córdova, Argentina

GSK Investigational Site
Buenos Aires, Argentina

GSK Investigational Site
Buenos Aires, Argentina

GSK Investigational Site
Cordoba, Argentina

GSK Investigational Site
Cordoba, Argentina

GSK Investigational Site
Brussel, Belgium

GSK Investigational Site
Yvoir, Belgium

GSK Investigational Site
Belo Horizonte, Minas Gerais, Brazil

GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil

GSK Investigational Site
São Paulo, Brazil

GSK Investigational Site
São Paulo, Brazil

GSK Investigational Site
São Paulo, Brazil

GSK Investigational Site
São Paulo, Brazil

GSK Investigational Site
Vancouver, British Columbia, Canada

GSK Investigational Site
Ottawa, Ontario, Canada

GSK Investigational Site
Ottawa, Ontario, Canada

GSK Investigational Site
Montréal, Quebec, Canada

GSK Investigational Site
QC, Quebec, Canada

GSK Investigational Site
St-Jerome, Quebec, Canada

GSK Investigational Site
Santiago, Chile

GSK Investigational Site
Santiago, Chile

GSK Investigational Site
Bogotá, Colombia

GSK Investigational Site
Amiens Cedex 1, France

GSK Investigational Site
Angers Cedex 9, France

GSK Investigational Site
Argenteuil, France

GSK Investigational Site
La Roche-Sur-Yon, France

GSK Investigational Site
La Tronche, France

GSK Investigational Site
Limoges Cedex, France

GSK Investigational Site
Melun, France

GSK Investigational Site
Paris, France

GSK Investigational Site
Pierre-Bénite, France

GSK Investigational Site
Strasbourg cedex, France

GSK Investigational Site
Strasbourg, France

GSK Investigational Site
Valenciennes Cedex, France

GSK Investigational Site
Aurangabad, India

GSK Investigational Site
Aurangabad, India

GSK Investigational Site
Hyderabad, India

GSK Investigational Site
Kolkata, India

GSK Investigational Site
Kolkata, India

GSK Investigational Site
Mumbai, India

GSK Investigational Site
Nagpur, India

GSK Investigational Site
New Delhi, India

GSK Investigational Site
Pune, India

GSK Investigational Site
Pune, India

GSK Investigational Site
Napoli, Campania, Italy

GSK Investigational Site
Aichi, Japan

GSK Investigational Site
Kanagawa, Japan

GSK Investigational Site
Kanagawa, Japan

GSK Investigational Site
Osaka, Japan

GSK Investigational Site
Saitama, Japan

GSK Investigational Site
Tokyo, Japan

GSK Investigational Site
Tokyo, Japan

GSK Investigational Site
Tokyo, Japan

GSK Investigational Site
Tokyo, Japan

GSK Investigational Site
Mexico City, Ciudad De Mexico, Mexico

GSK Investigational Site
Guadalajara, Jalisco, Mexico

GSK Investigational Site
Monterrey, Nuevo León, Mexico

GSK Investigational Site
Mexico, Mexico

GSK Investigational Site
Breda, Netherlands

GSK Investigational Site
Den Bosch, Netherlands

GSK Investigational Site
Enschede, Netherlands

GSK Investigational Site
Nijmegen, Netherlands

GSK Investigational Site
Rotterdam, Netherlands

GSK Investigational Site
Lima, Peru

GSK Investigational Site
Lima, Peru

GSK Investigational Site
Lima, Peru

GSK Investigational Site
Bydgoszcz, Poland

GSK Investigational Site
Krakow, Poland

GSK Investigational Site
Poznan, Poland

GSK Investigational Site
Warszawa, Poland

GSK Investigational Site
Wroclaw, Poland

GSK Investigational Site
Barnaul, Russian Federation

GSK Investigational Site
Chelyabinsk, Russian Federation

GSK Investigational Site
Ekaterinburg, Russian Federation

GSK Investigational Site
Moscow, Russian Federation

GSK Investigational Site
Nizhniy Novgorod, Russian Federation

GSK Investigational Site
Omsk, Russian Federation

GSK Investigational Site
Perm, Russian Federation

GSK Investigational Site
St. Petersburg, Russian Federation

GSK Investigational Site
Ufa, Russian Federation

GSK Investigational Site
Voronezh, Russian Federation

GSK Investigational Site
Benoni, Gauteng, South Africa

GSK Investigational Site
Johannesburg, Gauteng, South Africa

GSK Investigational Site
Durban, KwaZulu- Natal, South Africa

GSK Investigational Site
Panorama,, South Africa

GSK Investigational Site
Tygerberg, South Africa

GSK Investigational Site
Worcester, South Africa

GSK Investigational Site
Barcelona, Spain

GSK Investigational Site
L'Hospitalet de Llobregat, Spain

GSK Investigational Site
Logroño, Spain

GSK Investigational Site
Madrid, Spain

GSK Investigational Site
Madrid, Spain

GSK Investigational Site
Madrid, Spain

GSK Investigational Site
Madrid, Spain

GSK Investigational Site
San Sebastián De Los Reyes/Madrid, Spain

GSK Investigational Site
Manchester, Greater Manchester, United Kingdom

GSK Investigational Site
Liverpool, United Kingdom

GSK Investigational Site
Newcastle Upon Tyne, United Kingdom

GSK Clinical Trials, Study Director
GlaxoSmithKline

GlaxoSmithKline
NCT Number
Keywords
Covid-19
Otilimab
Ordinal scale
Coronavirus
GSK3196165
MeSH Terms
COVID-19
Severe Acute Respiratory Syndrome