Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID-19 Pneumonia

• ClinicalTrials.gov Identifier: NCT04329650
• Recruitment Status: Unknown
• First Posted: April 1, 2020
• Last Update Posted: April 17, 2020
• Sponsor: Judit Pich Martínez
• Information provided by (Responsible Party): Judit Pich Martínez, Fundacion Clinic per a la Recerca Biomédica

Study Description

Brief Summary:

In our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Siltuximab; Drug: Methylprednisolone	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2, Randomized, Open-label Study to Compare Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID19 Pneumonia
• Actual Study Start Date: April 15, 2020
• Estimated Primary Completion Date: May 20, 2020
• Estimated Study Completion Date: May 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Siltuximab 11mg/Kg	Drug: Siltuximab; A single-dose of 11mg/Kg of siltuximab will be administered by intravenous infusion.
Active Comparator: Methylprednisolone 250mg/24h	Drug: Methylprednisolone; A dose of 250mg/24 hours of methylprednisolone during 3 days followed by 30mg/24 hours during 3 days will be administered by intravenous infusion. If the patient is taken lopinavir/ritonavir, the dose will be 125 mg/ 24 hours during 3 days followed by 15mg/24 hours during 3 days.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients requiring ICU admission at any time within the study period. [ Time Frame: 29 days ]

Secondary Outcome Measures :

1. Days of stay in the ICU during the study period. [ Time Frame: 29 days ]
2. Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C, oral ≤ 37.2 ° C, or rectal or tympanic ≤ 37.8 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge. [ Time Frame: 29 days ]
3. Proportion of patients with a worsening requirement of supplemental oxygen at 29 days. days. [ Time Frame: 29 days ]
4. Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days. [ Time Frame: 29 days ]
5. Proportion of patients using mechanical ventilation at 29 days. [ Time Frame: 29 days ]
6. Days with use of mechanical ventilation at 29 days. [ Time Frame: 29 days ]
7. Days until the start of use of mechanical ventilation, non-invasive ventilation or use of high flow nasal cannula (if the patient have not previously required these interventions at the inclusion of the study) at 29 days. [ Time Frame: 29 days ]
8. Days of hospitalization among survivors at 29 days. [ Time Frame: 29 days ]
9. Mortality rate from any cause at 29 days. [ Time Frame: 29 days ]
10. Proportion of patients with serious adverse events at 29 days. [ Time Frame: 29 days ]
11. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic with grade 4 neutropenia (count neutrophil absolute <500 / mm3) at 29 days. [ Time Frame: 29 days ]
12. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic at 29 days. [ Time Frame: 29 days ]
13. Proportion of patients with grade 2 or higher adverse reactions related to the infusion of the sudy treatments at 29 days. [ Time Frame: 29 days ]
14. Proportion of patients with hypersensitivity reactions of grade 2 or higher related to the administration of the study treatments at 29 days. [ Time Frame: 29 days ]
15. Proportion of patients with gastrointestinal perforation at 29 days. [ Time Frame: 29 days ]
16. Proportion of patients with secondary severe infections confirmed by laboratory or worsening of existing infections at 29 days. [ Time Frame: 29 days ]
17. Changes from baseline in plasma leukocyte levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
18. Changes from baseline in plasma hemoglobin levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
19. Changes from baseline in plasma platelet at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
20. Changes from baseline in plasma creatinine levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
21. Changes from baseline in plasma total bilirubin levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
22. Proportion of patients with ALT≥ 3 times ULN (for patients with initial values normal) or> 3 times ULN AND at least 2 times more than the initial value (for patients with abnormal initial values) at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
23. Changes from baseline in plasma biomarkers (PCR, lymphocytes, ferritin, d-dimer and LDH) at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
24. Changes from baseline in chest Rx at days 1, 3 and 5. [ Time Frame: Days 1, 3 and 5 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18 years old.

2. Hospitalized patient (or documentation of a hospitalization plan if the patient is in an emergency department) with illness of more than 5 days of duration with evidence of pneumonia by chest radiography / tomography computed chest and meets at least one of the following requirements:

   1. Non-critical patient with pneumonia in radiological progression and / or
   2. Patient with progressive respiratory failure at the last 24-48 hours.
3. Laboratory confirmed SARS-CoV-2 infection (by PCR) or other commercialized analysis or public health in any sample collected 4 days before the randomization or COVID-19 criteria following the defined diagnostic criteria at that time in the center.
4. Patient with a maximum O2 support of 35%
5. Be willing and able to comply with the study related procedures / evaluations.
6. Women of childbearing potential * should have a negative serum pregnancy test before enrollment in the study and must commit to using methods highly effective contraceptives (intrauterine device, bilateral tubal occlusion, vasectomized couple and sexual abstinence).
7. Written informed consent. In case of inability of the patient to sign the informed consent, a verbal informed consent from the legal representative or family witness (or failing this, an impartial witness outside the investigator team) will be obtained by phone.

When circumstances so allow, participants should sign the consent form. The confirmation of the verbal informed consent will be documented in a document as evidence that verbal consent has been obtained.

Exclusion Criteria:

1. Patient who, in the investigator's opinion, is unlikely to survive> 48 hours after the inclusion in the study.

2. Presence of any of the following abnormal analytical values at the time of the inclusion in the study:

   • absolute neutrophil count less than 2000 / mm3;
   • AST or ALT> 5 times the upper limit of normality;
   • platelets <50,000 per mm3.
3. In active treatment with immunosuppressants or previous prolonged treatment (more 3 months) of oral corticosteroids for a disease not related to COVID-19 at a dose greater than 10 mg of prednisone or equivalent per day.
4. Known active tuberculosis or known history of tuberculosis uncompleted treatment.
5. Patients with active systemic bacterial and / or fungal infections.
6. Patients who have received previous treatment with IL6 inhibitor (tocilizumab, sarilumab).
7. Participants who, at the investigator's discretion, are not eligible to participate, regardless of the reason, including medical or clinical conditions, or participants potentially at risk of not following study procedures.
8. Patients who do not have entry criteria in the Intensive Care Unit.
9. Pregnancy or lactation.
10. Known hypersensitivity to siltuximab or to any of its excipients (histidine, histidine hydrochloride, polysorbate 80 and sucrose).

Contacts and Locations

Contacts

Contact: Felipe García, MD; +34932275400 ext 2884; fgarcia@clinic.cat

Locations

Spain

Hospital Germans Trias i Pujol; Not yet recruiting

Badalona, Spain

Contact: Roger Paredes, MD

Principal Investigator: Roger Paredes, MD

Hospital Clínic de Barcelona; Recruiting

Barcelona, Spain, 08036

Contact: Felipe García, MD

Principal Investigator: Felipe García, MD

Principal Investigator: Alex Soriano, MD

Hospital Universitario de Salamanca; Not yet recruiting

Salamanca, Spain

Contact: Cristina Carbonell, MD

Principal Investigator: Cristina Carbonell, MD

Hospital Universitari Mútua de Terrassa; Not yet recruiting

Terrassa, Spain

Contact: David Dalmau, MD

Principal Investigator: David Dalmau, MD

Sponsors and Collaborators

Judit Pich Martínez

Investigators

• Principal Investigator: Felipe García, MD; Hospital Clinic of Barcelona

More Information

• Responsible Party: Judit Pich Martínez, Clinical Research Manager, Fundacion Clinic per a la Recerca Biomédica
• ClinicalTrials.gov Identifier: NCT04329650
• Other Study ID Numbers: SILCOR-COVID-19
• First Posted: April 1, 2020
• Last Update Posted: April 17, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia; Respiratory Tract Infections; Infections; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Siltuximab; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents