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Trial record 1 of 1 for:    NCT04616586
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SILtuximab in Viral ARds (SILVAR) Study (SILVAR)

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ClinicalTrials.gov Identifier: NCT04616586
Recruitment Status : Recruiting
First Posted : November 5, 2020
Last Update Posted : January 12, 2021
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
EusaPharma (UK) Limited

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.

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Lung Diseases Pneumonia Respiratory Tract Infections Respiratory Tract Disease Drug: Siltuximab Other: Normal Saline Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 555 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model 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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
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)
Actual Study Start Date : November 13, 2020
Estimated Primary Completion Date : December 18, 2021
Estimated Study Completion Date : June 30, 2022


Arm Intervention/treatment
Experimental: Arm A
Drug - Siltuximab
Drug: Siltuximab
11 mg/kg IV administered over 1 hour
Other Name: Sylvant

Arm B
Comparator - Normal Saline
Other: Normal Saline
IV administered over 1 hour




Primary Outcome Measures :
  1. 28-day all-cause mortality [ Time Frame: Day 28 ]
    28-day all-cause mortality


Secondary Outcome Measures :
  1. Time to 7-category ordinal scale of clinical status improvement (T7COSCSI) [ Time Frame: Up to 60 days ]
    Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)

  2. Ventilator-free days (VFDs) within 28 days [ Time Frame: Up to 28 days ]
    Ventilator-free days (VFDs) within 28 days

  3. Organ failure-free days (OFFD) [ Time Frame: Up to 60 days ]
    Organ failure-free days (OFFD)

  4. Intensive care unit length of stay (ICU LOS) [ Time Frame: Up to 60 days ]
    Intensive care unit length of stay (ICU LOS)

  5. Hospital length of stay (HLOS) [ Time Frame: Up to 60 days ]
    Hospital length of stay (HLOS)

  6. In-hospital all-cause mortality (IHACM) [ Time Frame: Up to 60 days ]
    In-hospital all-cause mortality (IHACM)

  7. 60-day all-cause mortality (60DACM) [ Time Frame: Up to 60 days ]
    60-day all-cause mortality (60DACM)

  8. Time to oxygenation improvement (TOI) [ Time Frame: Up to 60 days ]
    Time to oxygenation improvement (TOI)

  9. Duration of supplemental oxygen (DSO) [ Time Frame: Up to 60 days ]
    Duration of supplemental oxygen (DSO)

  10. Chest radiographic improvement (CRI) [ Time Frame: Up to 60 days ]
    Chest radiographic improvement (CRI)

  11. Time to National Early Warning Score 2 improvement (TNEWS2I) [ Time Frame: Up to 60 days ]
    Time to National Early Warning Score 2 improvement (TNEWS2I)

  12. Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 60 days ]
    Treatment-emergent adverse events (TEAEs)

  13. Plasma siltuximab concentrations (PSCs) [ Time Frame: Up to 60 days ]
    Plasma siltuximab concentrations (PSCs)

  14. Anti-siltuximab antibodies (ASA) [ Time Frame: Up to 60 days ]
    Anti-siltuximab antibodies (ASA)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT04616586


Contacts
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Contact: Tina Karunaratne 617-834-3393 tina.karunaratne@eusapharma.com
Contact: Melahat Samali 978-390-1834 Melahat.Samali@eusapharma.com

Locations
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United States, Michigan
Sparrow Clinical Research Institute Recruiting
Lansing, Michigan, United States, 48912
Contact: Rajit Pahwa, MD    517-364-5728    rajit.pahwa@sparrow.org   
United States, North Carolina
Atrium Health Not yet recruiting
Charlotte, North Carolina, United States, 28202
Contact: Zainab Shahid, MD, PhD    980-442-6816    zainab.shahid@atriumhealth.org   
Contact: Nancy E Zeleniak    704-221-2021    Nancy.Zeleniak@atriumhealth.org   
Principal Investigator: Rajit Pahwa, MD         
Sponsors and Collaborators
EusaPharma (UK) Limited
Syneos Health
Investigators
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Principal Investigator: Zainab Shahid, MD, Ph.D Participating Site
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Responsible Party: EusaPharma (UK) Limited
ClinicalTrials.gov Identifier: NCT04616586    
Other Study ID Numbers: EUSA SYL 0004
First Posted: November 5, 2020    Key Record Dates
Last Update Posted: January 12, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 EusaPharma (UK) Limited:
Siltuximab
ARDS
Additional relevant MeSH terms:
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Respiratory Tract Infections
Lung Diseases
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Infection
Siltuximab
Antineoplastic Agents