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

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ClinicalTrials.gov Identifier: NCT04376684
Recruitment Status : Active, not recruiting
First Posted : May 6, 2020
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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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. 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. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of participants with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants 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.

Condition or disease Intervention/treatment Phase
Severe Acute Respiratory Syndrome Biological: Otilimab Biological: Placebo Drug: Standard of care Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.
Masking: Double (Participant, Investigator)
Masking Description: This is a double-blind study.
Primary Purpose: Treatment
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
Actual Study Start Date : May 28, 2020
Estimated Primary Completion Date : January 13, 2021
Estimated Study Completion Date : January 13, 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Participants receiving otilimab
Participants will receive a single dose of otilimab administered as an IV infusion in addition to standard of care.
 Biological: Otilimab
Otilimab will be administered once via IV route.

Drug: Standard of care
All participants will receive standard of care as per institutional protocol.
Placebo Comparator: Participants receiving placebo
Participants will receive a single dose of placebo administered as an IV infusion in addition to standard of care.
 Biological: Placebo
Placebo will consist of sterile 0.9 percent (%) sodium chloride solution administered once via IV route.

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


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of participants alive and free of respiratory failure at Day 28 [ Time Frame: Day 28 ]
    Participants are alive and free of respiratory failure if they are 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 is 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, high-flow 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.


Secondary Outcome Measures :
  1. Number of deaths due to all causes at Day 60 [ Time Frame: Day 60 ]
    Number of deaths due to all causes will be assessed.

  2. Time to number of deaths due to all causes up to Day 60 [ Time Frame: Up to Day 60 ]
    Time to death due to all causes will be assessed.

  3. Proportion of participants alive and free of respiratory failure at Days 7, 14, 42 and 60 [ Time Frame: Days 7, 14, 42, and 60 ]
    Participants alive and free of respiratory failure if they are 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 is 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, high-flow 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.

  4. Time to recovery from respiratory failure [ Time Frame: Up to Day 28 ]
    Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is 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, high-flow 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.

  5. Proportion of participants alive and independent of supplementary oxygen at Days 7, 14, 28, 42, and 60 [ Time Frame: Days 7, 14, 28, 42, and 60 ]
    Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is 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, high-flow 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.

  6. Time to last dependence on supplementary oxygen [ Time Frame: Up to Day 28 ]
    Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is 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, high-flow 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.

  7. Proportion of participants admitted to Intensive Care Unit (ICU) [ Time Frame: Up to Day 28 ]
    For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

  8. Time to final ICU discharge [ Time Frame: Up to Day 28 ]
    Defined as the time from dosing to when the participant is discharged from the ICU.

  9. Time to final hospital discharge [ Time Frame: Up to Day 28 ]
    Time from dosing to when a participant is discharged from the hospital.

  10. Number of participants with Adverse events (AEs) and Serious adverse events (SAEs) [ Time Frame: Up to Day 60 ]
    AEs and SAEs will be collected.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (e.g. 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, and one of the following conditions applies:

    1. Is a woman of non-childbearing potential (WONCBP)
    2. Or is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1% during the study intervention period and for at least 60 days after the last dose of study intervention (sexual abstinence is acceptable if it is the participant's normal practice).
    3. If not consistently on a highly effective method of contraception during hospitalization, the participant must agree to a highly effective contraception plan if discharged before Day 60.
    4. The investigator should evaluate potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relation to the first dose of study intervention.
    5. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at hospital admission or before the first dose of study intervention.
    6. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • 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], significant 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 (e.g. 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 (e.g. 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04376684


Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04376684    
Other Study ID Numbers: 214094
First Posted: May 6, 2020    Key Record Dates
Last Update Posted: December 22, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
COVID-19
Otilimab
Ordinal scale
Coronavirus
GSK3196165
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
 RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases