Covid-19 living Data

Otilimab vs Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-10-14

Studies description

Trial NCT04376684
Publication OSCAR - NCT04376684, Unpublished (2022) (results posted on registry)

Funding: Not reported/unclear
Conflict of interest: *

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Argentina, Belgium, Brazil, Canada, Chile, Colombia, France, India, Italy, Japan, Mexico, Netherlands, Peru, Poland, Russia, South Africa, Spain, UK, USA Follow-up duration (days): 60
Inclusion criteria	Participants aged 70 years or above at the time of obtaining informed consent Have positive SARS-CoV-2 result (any validated test, for example. RT-PCR [performed on an appropriate specimen for example. respiratory tract sample]) Hospitalized due to diagnosis of pneumonia (chest X-ray or CT scan consistent with COVID-19) Developing new onset of oxygenation impairment requiring any of the following: high-flow oxygen (>=15L/min) or non-invasive ventilation (for example. CPAP, BiPAP) or mechanical ventilation <=48 hours prior to dose 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 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
Interventions
	Treatment Otilimab 90 mg IV infusion single dose for 1 hour
	Control Placebo
Participants
	Randomized participants : Placebo=175 Otilimab=175
	Characteristics of participants N= 350 Mean age : NR 202 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=* Critical: n=*
Primary outcome
	In the register Percentage of Participants Alive and Free of Respiratory Failure at Day 28 [ Time Frame: 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.
	In the report NR
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively. The report is for part 2 (phase 3) of a 2-part study. This additional cohort was added to confirm the efficacy and safety in part 1 (phase 2).

Trial NCT04376684
Publication OSCAR - Patel J, medRxiv (2021) (preprint)
Dates: 2020-05-28 to 2020-11-15
Funding: Private (GSK)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Argentina, Belgium, Brazil, Canada, Chile, France, India, Japan, Mexico, Netherlands, Peru, Poland, Russia, South Africa, Spain, UK, USA Follow-up duration (days): 60
Inclusion criteria	Hospitalized adult patients (≥18 to ≤79 years of age) confirmed SARS-CoV-2 pneumonia new onset hypoxemia requiring any of high-flow oxygen (≥15 L/min), non-invasive ventilation or mechanical ventilation (MV duration ≤48 hours prior to dose) increased biological markers of systemic inflammation (C-reactive protein or serum ferritin above local upper limit of normal)
Exclusion criteria	Death considered likely within 48 hours multiple organ failure according to the investigator’s opinion or a Sequential Organ Failure Assessment (SOFA) score >10 if in the ICU or use of extracorporeal membrane oxygenation, hemofiltration/dialysis, high-dose (>0.15 μg/kg/min) noradrenaline (or equivalent) or >1 vasopressor.
Interventions
	Treatment Otilimab 90 mg single (1 hour) intravenous infusion
	Control Placebo
Participants
	Randomized participants : Otilimab=403 Placebo=403
	Characteristics of participants N= 806 Mean age : NR 577 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=622 Critical: n=178
Primary outcome
	In the register Proportion of participants alive and free of respiratory failure at Day 28 (measured by an 8-point ordinal scale).
	In the report The proportion of patients alive and free of respiratory failure (clinical status Categories 1, 2, 3, or 4) at Day 28
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. There were no substantive differences between the article and the trial registry, protocol and statistical analysis plan in population, procedures, intervention and outcomes. The primary outcome indicated in the registry reflects the primary outcome reported in the paper. The report is for part 1 of a 2-part study. The target sample size in the trial registry appears to be for both parts 1 and 2. Part 1 achieved the sample size specified in the protocol and methods section. This study was updated on the 28th of September 2022 with data extracted from the registry.