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

NCT04376684 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 214094
• Study Type: interventional
• Target: 1,156
• Locations: 19 countries
• Sites: 120

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.

Conditions

Severe Acute Respiratory Syndrome

Keywords

COVID-19; Otilimab; Ordinal scale; Coronavirus; GSK3196165

Outcome Measures

Primary Outcomes (2)

• Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28

  Participants were considered alive and free of respiratory failure if they were in category 1, 2, 3, or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (greater than or equal to \[\>=\]15 liters per minute \[L/min\]), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.

  At Day 28

• Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28

  Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (\>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.

  At Day 28

Secondary Outcomes (36)

• Part 1: Number of Participants Who Died Due to All Causes at Day 60

  At Day 60

• Part 2: Number of Participants Who Died Due to All Causes at Day 28

  At Day 28

• Part 2: Number of Participants Who Died Due to All Causes at Day 60

  At Day 60

• Part 1: Time to Death Due to All Causes up to Day 60

  Up to Day 60

• Part 2: Time to Death Due to All Causes up to Day 60

  Up to Day 60

Study Arms (4)

Part 1: Participants receiving otilimab

EXPERIMENTAL

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.

Biological: Otilimab; Drug: Standard of care

Part 1: Participants receiving placebo 1

PLACEBO COMPARATOR

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.

Biological: Placebo 1; Drug: Standard of care

Part 2: Participants receiving otilimab

EXPERIMENTAL

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.

Biological: Otilimab; Drug: Standard of care

Part 2: Participants receiving placebo 2

PLACEBO COMPARATOR

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.

Biological: Placebo 2; Drug: Standard of care

Interventions

Otilimab BIOLOGICAL

Otilimab will be administered once via IV route.

Part 1: Participants receiving otilimab; Part 2: Participants receiving otilimab

Placebo 1 BIOLOGICAL

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

Part 1: Participants receiving placebo 1

Placebo 2 BIOLOGICAL

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

Part 2: Participants receiving placebo 2

Standard of care DRUG

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

Part 1: Participants receiving otilimab; Part 1: Participants receiving placebo 1; Part 2: Participants receiving otilimab; Part 2: Participants receiving placebo 2

Eligibility Criteria

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

You may qualify if:

• Participants aged \>=18 years and \<=79 years at the time of obtaining informed consent.
• Participants must:
• have positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) result (any validated test, for example. reverse transcription polymerase chain reaction \[RT-PCR\] \[performed on an appropriate specimen; for example: respiratory tract sample\])
• and be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography \[CT\] scan consistent with COVID-19)
• and be developing new onset of oxygenation impairment requiring any of the following:
• high-flow oxygen (\>=15L/min)
• non-invasive ventilation (for example. CPAP, BIPAP)
• mechanical ventilation \<=48 hours prior to dose
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (120)

GSK Investigational Site

Mobile, Alabama, 36608, United States

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GSK Investigational Site

Little Rock, Arkansas, 72205, United States

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GSK Investigational Site

Sacramento, California, 95819, United States

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GSK Investigational Site

Torrance, California, 90502, United States

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Gainesville, Florida, 32608, United States

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GSK Investigational Site

Winfield, Illinois, 60190, United States

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Baltimore, Maryland, 21201, United States

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GSK Investigational Site

Germantown, Maryland, 20876, United States

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GSK Investigational Site

Silver Spring, Maryland, 20910, United States

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Saint Louis Park, Minnesota, 55426, United States

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Saint Paul, Minnesota, 55101, United States

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Jackson, Mississippi, 39216, United States

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Reno, Nevada, 89502, United States

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Buffalo, New York, 14215-1199, United States

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Charlotte, North Carolina, 28203, United States

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Toledo, Ohio, 43608, United States

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Doylestown, Pennsylvania, 18901, United States

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Philadelphia, Pennsylvania, 19140, United States

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Roanoke, Virginia, 24017, United States

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Tacoma, Washington, 98405, United States

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Milwaukee, Wisconsin, 53295, United States

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Munro, Buenos Aires, 1605, Argentina

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Córdoba, Córdoba Province, X5000, Argentina

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Buenos Aires, 1842, Argentina

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Buenos Aires, C1039AAO, Argentina

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Córdoba, 5000, Argentina

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Córdoba, X5002AOQ, Argentina

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Brussels, 1090, Belgium

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Yvoir, 5530, Belgium

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Belo Horizonte, Minas Gerais, 30130-100, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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São Paulo, 01246-090, Brazil

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São Paulo, 01323903, Brazil

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São Paulo, 04037-003, Brazil

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São Paulo, 05403-010, Brazil

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Vancouver, British Columbia, V6Z 1Y6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Ottawa, Ontario, K1Y 4E9, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, J5R 6J5, Canada

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Saint-Jérôme, Quebec, J7Z 5T3, Canada

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Santiago, 7630000, Chile

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Santiago, 8900085, Chile

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Bogotá, 111971, Colombia

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Amiens, 80054, France

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Angers, 49933, France

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GSK Investigational Site

Argenteuil, 95100, France

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GSK Investigational Site

La Roche-sur-Yon, 85925, France

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GSK Investigational Site

La Tronche, 38700, France

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Limoges, 87042, France

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Melun, 77000, France

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Paris, 75013, France

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Pierre-Bénite, 69495, France

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Strasbourg, 67000, France

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Strasbourg, 67098, France

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Valenciennes, 59322, France

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GSK Investigational Site

Aurangabad, 431001, India

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Aurangabad, 431003, India

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Hyderabad, 500018, India

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Kolkata, 700094, India

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Kolkata, 700099, India

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Mumbai, 400034, India

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Nagpur, 440003, India

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New Delhi, 110017, India

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GSK Investigational Site

Pune, 411001, India

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Pune, 411013, India

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Napoli, Campania, 80100, Italy

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Aichi, 470-1192, Japan

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Kanagawa, 231-8682, Japan

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Kanagawa, 251-0041, Japan

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Osaka, 534-0021, Japan

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Saitama, 350-0495, Japan

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Tokyo, 113-8519, Japan

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Tokyo, 150-8935, Japan

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Tokyo, 162-8543, Japan

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Tokyo, 162-8655, Japan

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Guadalajara, Jalisco, 44280, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Monterrey, Nuevo León, 64710, Mexico

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México, 14000, Mexico

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's-Hertogenbosch, 5223 GZ, Netherlands

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Breda, 4818 CK, Netherlands

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Enschede, 7512 KZ, Netherlands

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Nijmegen, 6532 SZ, Netherlands

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Rotterdam, 3083 AN, Netherlands

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Lima, Callao 2, Peru

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Lima, Lima 11, Peru

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Lima, Lima 1, Peru

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Bydgoszcz, 85-030, Poland

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Krakow, 30-688, Poland

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Poznan, 61-285, Poland

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Warsaw, 02-507, Poland

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Wroclaw, 51-149, Poland

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Barnaul, 656045, Russia

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Chelyabinsk, 454034, Russia

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Moscow, 111539, Russia

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Nizhny Novgorod, 603011, Russia

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GSK Investigational Site

Omsk, 644111, Russia

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GSK Investigational Site

Perm, 614990, Russia

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Saint Petersburg, 191104, Russia

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Ufa, 450083, Russia

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Voronezh, 394066, Russia

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Yekaterinburg, 620039, Russia

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Benoni, Gauteng, 1501, South Africa

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Johannesburg, Gauteng, 2193, South Africa

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Durban, KwaZulu-Natal, 4052, South Africa

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Panorama, 7500, South Africa

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Tygerberg, 7505, South Africa

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GSK Investigational Site

Worcester, 6850, South Africa

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GSK Investigational Site

Barcelona, 08003, Spain

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GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

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GSK Investigational Site

Logroño, 26006, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28055, Spain

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GSK Investigational Site

San Sebastián de Los Reyes/Madrid, 28702, Spain

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GSK Investigational Site

Manchester, Greater Manchester, M13 9WL, United Kingdom

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GSK Investigational Site

Newcastle, Northumberland, NE2 4HH, United Kingdom

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GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

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Related Publications (1)

• 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.

  PMID: 36229048 BACKGROUND

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections

Interventions

Otilimab; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 6, 2020
• Study Start: May 28, 2020
• Primary Completion: July 15, 2021
• Study Completion: August 16, 2021
• Last Updated: September 23, 2024
• Results First Posted: March 9, 2022

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

CA (6); FR (12); JP (9); ZA (6); IT (1); US (21); AR (6); NL (5); ES (8); IN (10); BR (6); BE (2); CL (2); ME (4); PE (3); CO (1); RU (10); PL (5); GB (3)