SILtuximab in Viral ARds (SILVAR) Study (SILVAR)
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| ClinicalTrials.gov Identifier: NCT04616586 |
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Recruitment Status :
Recruiting
First Posted : November 5, 2020
Last Update Posted : January 12, 2021
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| 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 |
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.
| 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 |
|---|---|
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Experimental: Arm A
Drug - Siltuximab
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Drug: Siltuximab
11 mg/kg IV administered over 1 hour
Other Name: Sylvant |
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Arm B
Comparator - Normal Saline
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Other: Normal Saline
IV administered over 1 hour |
- 28-day all-cause mortality [ Time Frame: Day 28 ]28-day all-cause mortality
- 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)
- Ventilator-free days (VFDs) within 28 days [ Time Frame: Up to 28 days ]Ventilator-free days (VFDs) within 28 days
- Organ failure-free days (OFFD) [ Time Frame: Up to 60 days ]Organ failure-free days (OFFD)
- Intensive care unit length of stay (ICU LOS) [ Time Frame: Up to 60 days ]Intensive care unit length of stay (ICU LOS)
- Hospital length of stay (HLOS) [ Time Frame: Up to 60 days ]Hospital length of stay (HLOS)
- In-hospital all-cause mortality (IHACM) [ Time Frame: Up to 60 days ]In-hospital all-cause mortality (IHACM)
- 60-day all-cause mortality (60DACM) [ Time Frame: Up to 60 days ]60-day all-cause mortality (60DACM)
- Time to oxygenation improvement (TOI) [ Time Frame: Up to 60 days ]Time to oxygenation improvement (TOI)
- Duration of supplemental oxygen (DSO) [ Time Frame: Up to 60 days ]Duration of supplemental oxygen (DSO)
- Chest radiographic improvement (CRI) [ Time Frame: Up to 60 days ]Chest radiographic improvement (CRI)
- Time to National Early Warning Score 2 improvement (TNEWS2I) [ Time Frame: Up to 60 days ]Time to National Early Warning Score 2 improvement (TNEWS2I)
- Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 60 days ]Treatment-emergent adverse events (TEAEs)
- Plasma siltuximab concentrations (PSCs) [ Time Frame: Up to 60 days ]Plasma siltuximab concentrations (PSCs)
- Anti-siltuximab antibodies (ASA) [ Time Frame: Up to 60 days ]Anti-siltuximab antibodies (ASA)
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.
| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
| Contact: Tina Karunaratne | 617-834-3393 | tina.karunaratne@eusapharma.com | |
| Contact: Melahat Samali | 978-390-1834 | Melahat.Samali@eusapharma.com |
| 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 | |
| Principal Investigator: | Zainab Shahid, MD, Ph.D | Participating Site |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Siltuximab ARDS |
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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 |