SILtuximab in Viral ARds (SILVAR) Study

NCT04616586 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: EUSA SYL 0004
• Study Type: interventional
• Target: 555
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Siltuximab; ARDS

Outcome Measures

Primary Outcomes (1)

• 28-day all-cause mortality

  28-day all-cause mortality

  Day 28

Secondary Outcomes (14)

• Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)

  Up to 60 days

• Ventilator-free days (VFDs) within 28 days

  Up to 28 days

• Organ failure-free days (OFFD)

  Up to 60 days

• Intensive care unit length of stay (ICU LOS)

  Up to 60 days

• Hospital length of stay (HLOS)

  Up to 60 days

Study Arms (2)

Arm A

EXPERIMENTAL

Drug - Siltuximab

Drug: Siltuximab

Arm B

OTHER

Comparator - Normal Saline

Other: Normal Saline

Interventions

Siltuximab DRUG

11 mg/kg IV administered over 1 hour

Also known as: Sylvant

Arm A

Normal Saline OTHER

IV administered over 1 hour

Arm B

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RECORDATI GROUP: lead
• Syneos Health: collaborator

Study Sites (2)

Sparrow Clinical Research Institute

Lansing, Michigan, 48912, United States

Location

Atrium Health

Charlotte, North Carolina, 28202, United States

Location

MeSH Terms

Conditions

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

Interventions

siltuximab; Saline Solution

Condition Hierarchy (Ancestors)

Respiration Disorders; Infections

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Zainab Shahid, MD, Ph.D

  Participating Site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: At all times, randomized study treatment assignment information will be kept confidential and will not be released to the patient, investigator, the study staff (except the pharmacist), or the Sponsor's Study Team until following the conclusion of the study, except as described below. At the initiation of the study, the study site will be instructed on procedures for breaking the blind. Blinding codes should be broken only in emergency situations for reasons of patient safety. If a patient has an AE that may be considered treatment-related, treatment for the AE should be administered as if the patient is receiving siltuximab. Whenever possible, the investigator should contact the Sponsor's Medical Monitor before breaking the blind. When the blind for a patient has been broken, the reason must be fully documented. The patient for whom the blind has been broken will not receive further doses of study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 10, 2020
• First Posted: November 5, 2020
• Study Start: November 13, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: April 19, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)