SILtuximab in Viral ARds (SILVAR) Study

Pneumonia Clinical Trial

— SILVAR  

Official title:

A Study Comparing the Efficacy and Safety of Standard of Care With or Without Siltuximab in Selected Hospitalized Patients With Viral Acute Respiratory Distress Syndrome (SILVAR)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04616586
• Other study ID #: EUSA SYL 0004
• Status: Terminated
• Phase: Phase 3
• Start date: November 13, 2020
• Est. completion date: April 1, 2021

Study information

• Verified date: January 2021
• Source: EusaPharma (UK) Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of siltuximab compared with normal saline in combination with standard of care (SOC) in selected hospitalized patients with COVID-19 previously treated with corticosteroids or another respiratory virus infection associated with acute respiratory distress syndrome (ARDS) and elevated C-reactive protein (CRP) levels.

Description:

This is a prospective, multicenter, randomized (2:1), double-blind, parallel-arm, placebo-controlled, Phase 3 clinical trial of 1-3 doses of siltuximab 11 mg/kg IV over 1 hour plus SOC vs. matched-volume normal saline (NS) IV over 1 hour plus SOC in 555 patients with SARS CoV-2 previously treated with corticosteroids or another respiratory virus infection with elevated CRP levels who have developed serious respiratory complications.

The randomization will be stratified by age (<65, ≥65 years), respiratory virus infection (confirmed SARS-CoV-2, other), and MIV status (yes, no). Crossover between treatment arms will not be allowed.

All patients will receive ARDS SOC following the official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline13 and/or the World Health Organization's (WHO's) clinical management of severe acute respiratory infection when COVID-19 disease is suspected (WHO Interim Guidance 202014 or other local guidance). Patients may continue receiving their corticosteroid (up to a cumulative maximum dexamethasone or equivalent dose of 60 mg [except to treat treatment-emergent reactions or comorbid conditions]) or antiviral therapy (except aminoquinoline compounds and convalescent plasma) at the same or lower doses if started at least 4 days (corticosteroid therapy) or at least 2 days (antiviral therapy) prior to randomization. Patients randomized to Arm A will additionally receive siltuximab 11 mg/kg IV administered over 1 hour, while patients randomized to Arm B will additionally receive IV NS administered over 1 hour, with opportunity to repeat their assigned study treatment once or twice at least 2 days apart on or after Day 3 as their clinical condition and/or laboratory testing dictate.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 555
• Est. completion date: April 1, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Positive microbiological evidence of SARS-CoV-2 or another respiratory virus infection (eg, other coronaviruses, respiratory syncytial virus, influenza virus) following institutional diagnostic standards

• Clinical and radiological diagnosis of pulmonary infection requiring noninvasive or mechanical invasive ventilatory support plus administration of rising supplemental oxygen concentrations

• Treatment of SARS-CoV-2-infected patients with dexamethasone (or equivalent) administered by mouth or intravenous (IV) injection

• Diagnosis of ARDS (PaO2/FiO2 =200 with positive end-expiratory pressure =5 cmH2O) in accordance with Berlin 2012 criteria1 (measured on or after the fourth day after the start of corticosteroid therapy in those patients for whom it was prescribed)

• Serum CRP level greater than upper limit of normal (measured on or after the third day after the start of corticosteroid therapy in those patients for whom it was prescribed) on 2 consecutive days

• Age =12 years

Exclusion Criteria:

• Active bacterial or fungal infection, human immunodeficiency virus (HIV), HHV, Epstein-Barr virus, or other non-respiratory virus infection, or tuberculosis requiring initiation of anti-infective therapy

• Prior treatment with an agent targeting the IL-6 signaling pathway

• Current treatment in another therapeutic clinical trial (other than expanded remdesivir access protocol)

• Start of new immunosuppressive therapy (including but not limited to corticosteroids and cytokine signaling pathway inhibitors) within 4 days prior to study entry (randomization); start of new antiviral treatment (including but not limited to nucleoside analogues, aminoquinoline compounds, and convalescent plasma) within 2 days prior to randomization; or received a live vaccine at any time prior to randomization, or plan to receive a live vaccine during the study

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Lung Diseases
• Pneumonia
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Tract Disease
• Respiratory Tract Diseases
• Respiratory Tract Infections

Intervention

Drug:
• Siltuximab
11 mg/kg IV administered over 1 hour

Other:
• Normal Saline
IV administered over 1 hour

Locations

Country	Name	City	State
United States	Atrium Health	Charlotte	North Carolina
United States	Sparrow Clinical Research Institute	Lansing	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
EusaPharma (UK) Limited	Syneos Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day all-cause mortality	28-day all-cause mortality	Day 28
Secondary	Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)	Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)	Up to 60 days
Secondary	Ventilator-free days (VFDs) within 28 days	Ventilator-free days (VFDs) within 28 days	Up to 28 days
Secondary	Organ failure-free days (OFFD)	Organ failure-free days (OFFD)	Up to 60 days
Secondary	Intensive care unit length of stay (ICU LOS)	Intensive care unit length of stay (ICU LOS)	Up to 60 days
Secondary	Hospital length of stay (HLOS)	Hospital length of stay (HLOS)	Up to 60 days
Secondary	In-hospital all-cause mortality (IHACM)	In-hospital all-cause mortality (IHACM)	Up to 60 days
Secondary	60-day all-cause mortality (60DACM)	60-day all-cause mortality (60DACM)	Up to 60 days
Secondary	Time to oxygenation improvement (TOI)	Time to oxygenation improvement (TOI)	Up to 60 days
Secondary	Duration of supplemental oxygen (DSO)	Duration of supplemental oxygen (DSO)	Up to 60 days
Secondary	Chest radiographic improvement (CRI)	Chest radiographic improvement (CRI)	Up to 60 days
Secondary	Time to National Early Warning Score 2 improvement (TNEWS2I)	Time to National Early Warning Score 2 improvement (TNEWS2I)	Up to 60 days
Secondary	Treatment-emergent adverse events (TEAEs)	Treatment-emergent adverse events (TEAEs)	Up to 60 days
Secondary	Plasma siltuximab concentrations (PSCs)	Plasma siltuximab concentrations (PSCs)	Up to 60 days
Secondary	Anti-siltuximab antibodies (ASA)	Anti-siltuximab antibodies (ASA)	Up to 60 days