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Phase 2, randomized, open-label study to compare the efficacy and safety of siltuximab vs. corticosteroids in hospitalized patients with COVID19 pneumonia

Trial Profile

Phase 2, randomized, open-label study to compare the efficacy and safety of siltuximab vs. corticosteroids in hospitalized patients with COVID19 pneumonia

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 08 Jul 2020

At a glance

  • Drugs Siltuximab (Primary) ; Lopinavir/ritonavir; Methylprednisolone
  • Indications COVID 2019 infections; Pneumonia
  • Focus Therapeutic Use
  • Most Recent Events

    • 08 Jul 2020 According to European Clinical Trials Database record, this study is suspended in Spain.
    • 16 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 15 Apr 2020 Planned number of patients changed from 100 to 200.

Trial Overview

Purpose

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.

Primary Endpoints

Proportion of patients requiring ICU admission at any time within the study period.

time_frame: 29 days

Other Endpoints

1. Days of stay in the ICU during the study period.
2. Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge, whichever occurs first
3. Proportion of patients with a worsening requirement of supplemental oxygen at 29 days.
4. Days until improvement in oxygenation (SpO2 / FiO2 increase of 50 or more in comparison with SpO2 / FiO2 nadir) for at least 48 hours, depending on clinical severity at 29 days.
5. Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days.
6. Proportion of patients using mechanical ventilation at 29 days.
7. Days with use of mechanical ventilation at 29 days.
8. 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.
9. Days of hospitalization among survivors at 29 days.
10. Mortality rate from any cause at 29 days.
11. Proportion of patients with serious adverse events at 29 days.
12. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic with grade 4 neutropenia (count neutrophil absolute [RAN] <500 / mm3) at 29 days.
13. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic at 29 days.
14. Proportion of patients with grade 2 or higher adverse reactions related to the infusion of the sudy treatments at 29 days.
15. Proportion of patients with hypersensitivity reactions of grade 2 or higher related to the administration of the study treatments at 29 days.
16. Proportion of patients with gastrointestinal perforation at 29 days.
17. Proportion of patients with secondary severe infections confirmed by laboratory or worsening of existing infections at 29 days.
18. Changes from baseline in plasma leukocyte levels at days 1, 3, 5, 7 and 9.
19. Changes from baseline in plasma hemoglobin levels at days 1, 3, 5, 7 and 9.
20. Changes from baseline in plasma platelet at days 1, 3, 5, 7 and 9.
21. Changes from baseline in plasma creatinine levels at days 1, 3, 5, 7 and 9.
22. Changes from baseline in plasma total bilirubin levels at days 1, 3, 5, 7 and 9.
23. 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.
24. Changes from baseline in plasma biomarkers (PCR, lymphocytes, ferritin, d-dimer and LDH) at days 1, 3, 5, 7 and 9.
25. Changes from baseline in chest Rx at days 1, 3 and 5.

Timepoint: 29 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 200

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient 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.

Patient 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).

Trial Details

Identifiers

Identifier Owner
NCT04329650 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001413-20 European Clinical Trials Database
SILCOR-COVID19 -

Trial Dates

  • Initiation Dates

    Planned : 01 Apr 2020

    Actual : 15 Apr 2020

  • Primary Completion Dates

    Planned : 20 May 2020

  • End Dates

    Planned : 20 May 2020

Other Details

  • Design open; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Spain
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
Lopinavir/ritonavir Intravenous Infusion
Methylprednisolone Intravenous Infusion
SiltuximabPrimary Drug Intravenous Infusion

Siltuximab 11mg/Kg

Drug: Siltuximab (A single-dose of 11mg/Kg of siltuximab will be administered by intravenous infusion.)

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.)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Alex Soriano, MD Hospital Clínic de Barcelona Spain
Cristina Carbonell, MD Hospital Universitario de Salamanca Spain
David Dalmau, MD Hospital Universitari Mútua de Terrassa Spain
Felipe García, MD
+34932275400 Ext: 2884 fgarcia@clinic.cat
show details
Hospital Clínic de Barcelona Spain
Roger Paredes, MD Hospital Germans Trias i Pujol Spain

Centres

Centre Name Location Trial Centre Country
Hospital Clínic de Barcelona Barcelona Spain
Hospital Germans Trias i Pujol Badalona Spain
Hospital Universitari Mútua de Terrassa Terrassa Spain
Hospital Universitario de Salamanca Salamanca Spain
Judit Pich Martínez
-
-

Trial History

Event Date Event Type Comment
08 Jul 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 08 Jul 2020
08 Jul 2020 Other trial event According to European Clinical Trials Database record, this study is suspended in Spain. Updated 08 Jul 2020
20 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 20 Apr 2020
17 Apr 2020 Other trial event New source identified and integrated (European Clinical Trials Database: EudraCT2020-001413-20 ). Updated 17 Apr 2020
16 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 17 Apr 2020
15 Apr 2020 Other trial event Planned number of patients changed from 100 to 200. Updated 20 Apr 2020
03 Apr 2020 New trial record New trial record Updated 03 Apr 2020

References

  1. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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