Clinical trial NCT04376684: Investigating Otilimab in Patients With Severe Pulmonary COVID-19 Related Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Acute Respiratory Syndrome
Keywords: COVID-19
Otilimab
Ordinal scale
Coronavirus
GSK3196165
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-05-06
Enrollment: 1156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.
Primary purpose: TREATMENT

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 \[\<=\] 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.


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.

Primary outcomes:
measure: Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
timeFrame: At Day 28
measure: Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
timeFrame: At Day 28
Secondary outcomes:
measure: Part 1: Number of Participants Who Died Due to All Causes at Day 60
timeFrame: At Day 60
measure: Part 2: Number of Participants Who Died Due to All Causes at Day 28
timeFrame: At Day 28
measure: Part 2: Number of Participants Who Died Due to All Causes at Day 60
timeFrame: At Day 60
measure: Part 1: Time to Death Due to All Causes up to Day 60
timeFrame: Up to Day 60
measure: Part 2: Time to Death Due to All Causes up to Day 60
timeFrame: Up to Day 60
measure: Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
timeFrame: At Day 7
measure: Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
timeFrame: At Day 14
measure: Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
timeFrame: At Day 42
measure: Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
timeFrame: At Day 60
measure: Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
timeFrame: At Day 7
measure: Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
timeFrame: At Day 14
measure: Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
timeFrame: At Day 42
measure: Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
timeFrame: At Day 60
measure: Part 1: Time to Recovery From Respiratory Failure up to Day 28
timeFrame: Up to Day 28
measure: Part 2: Time to Recovery From Respiratory Failure up to Day 28
timeFrame: Up to Day 28
measure: Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
timeFrame: At Day 7
measure: Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
timeFrame: At Day 14
measure: Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
timeFrame: At Day 28
measure: Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
timeFrame: At Day 42
measure: Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
timeFrame: At Day 60
measure: Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
timeFrame: At Day 7
measure: Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
timeFrame: At Day 14
measure: Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
timeFrame: At Day 28
measure: Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
timeFrame: At Day 42
measure: Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
timeFrame: At Day 60
measure: Part 1: Time to Last Dependence on Supplementary Oxygen
timeFrame: Up to Day 28
measure: Part 2: Time to Last Dependence on Supplementary Oxygen
timeFrame: Up to Day 28
measure: Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28
timeFrame: Up to Day 28
measure: Part 1: Time to Final ICU Discharge
timeFrame: Up to Day 28
measure: Part 2: Time to Final ICU Discharge
timeFrame: Up to Day 28
measure: Part 1: Time to First Discharge From Investigator Site up to Day 60
timeFrame: Up to Day 60
measure: Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60
timeFrame: Up to Day 60
measure: Part 2: Time to First Discharge From Investigator Site up to Day 60
timeFrame: Up to Day 60
measure: Part 2: Time to First Discharge to Non-hospitalized Residence
timeFrame: Up to Day 60
measure: Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)
timeFrame: Up to Day 60
measure: Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs
timeFrame: Up to Day 60
Other outcomes:
Locations:
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
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state: California
city: Gainesville
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state: Florida
city: Winfield
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city: Baltimore
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city: Germantown
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city: Roanoke
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city: Milwaukee
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city: Munro
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city: Cordoba
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city: Buenos Aires
country: Argentina
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country: Argentina
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country: Belgium
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state: Minas Gerais
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city: São Paulo
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city: Strasbourg cedex
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city: Strasbourg
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country: India
facility: GSK Investigational Site
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country: India
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city: Hyderabad
country: India
facility: GSK Investigational Site
city: Kolkata
country: India
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city: Kolkata
country: India
facility: GSK Investigational Site
city: Mumbai
country: India
facility: GSK Investigational Site
city: Nagpur
country: India
facility: GSK Investigational Site
city: New Delhi
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
state: Ciudad De Mexico
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Den Bosch
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Nizhniy Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Perm
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Ufa
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Benoni
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: GSK Investigational Site
state: KwaZulu- Natal
city: Panorama,
country: South Africa
facility: GSK Investigational Site
city: Tygerberg
country: South Africa
facility: GSK Investigational Site
city: Worcester
country: South Africa
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: GSK Investigational Site
city: Logroño
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: San Sebastián De Los Reyes/Madrid
country: Spain
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Greater Manchester
city: Newcastle
country: United Kingdom
facility: GSK Investigational Site
state: Northumberland
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.