SILtuximab in Viral ARds (SILVAR) Study

NCT ID: NCT04616586

Last Updated: 2021-04-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 555 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-13
• Study Completion Date: 2021-04-01

Brief 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.

Detailed 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.

Conditions

Acute Respiratory Distress Syndrome; Lung Diseases; Pneumonia; Respiratory Tract Infections; Respiratory Tract Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A

Drug - Siltuximab

Group Type: EXPERIMENTAL

Siltuximab

Intervention Type: DRUG

11 mg/kg IV administered over 1 hour

Arm B

Comparator - Normal Saline

Group Type: OTHER

Normal Saline

Intervention Type: OTHER

IV administered over 1 hour

Interventions

Siltuximab

11 mg/kg IV administered over 1 hour

Intervention Type: DRUG

Normal Saline

IV administered over 1 hour

Intervention Type: OTHER

Other Intervention Names

Sylvant

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syneos Health

OTHER

Sponsor Role: collaborator

RECORDATI GROUP

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zainab Shahid, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Participating Site

Locations

Sparrow Clinical Research Institute

Lansing, Michigan, United States

Atrium Health

Charlotte, North Carolina, United States

Countries

United States

Other Identifiers

EUSA SYL 0004

Identifier Type: -

Identifier Source: org_study_id