Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19 (STRIKESARS)

• ClinicalTrials.gov Identifier: NCT04661527
• Recruitment Status: Recruiting
• First Posted: December 10, 2020
• Last Update Posted: December 16, 2020
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborators: Sanofi; Hospital Universitario Infanta Leonor
• Information provided by (Responsible Party): Clinica Universidad de Navarra, Universidad de Navarra

Study Description

Brief Summary:

Phase II, one-arm, open label, multicentric study, to evaluate treatment of severe COVID-19 with sarilumab prior to entry into the intensive care unit (ICU).

Condition or disease	Intervention/treatment	Phase
COVID-19 Drug Treatment	Drug: Sarilumab	Phase 2

Detailed Description:

Phase II, one-arm, open label, multicentric study, to evaluate treatment of severe COVID-19 with sarilumab prior to entry into the intensive care unit (ICU).

The primary objective of the trial is to evaluate the impact of sarilumab on the progression of COVID 19-associated respiratory failure as measured by the change in a severity rating on a 7-point severity index. Secondary objectives include the evaluation of safety of the drug and the assessment of the impact of Sarilumab on markers of systemic inflammation and the coagulation cascade, on mortality, and on oxygenation.

The trial has two phases. Firstly, patients with pneumonia in the setting of COVID-19 who meet inclusion criteria and have no exclusion criteria will be treated with 2 doses of 200 mg IV of Sarilumab in 24 hours. After internal review, if no AE are detected and if there is no significant improvement, the next 55 patients will be treated with two doses of 400 mg IV in 24 hours.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Phase II, one-arm, open label, multicentric study, to evaluate treatment of severe COVID-19 with sarilumab prior to entry into the intensive care unit (ICU)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19
• Actual Study Start Date: April 22, 2020
• Estimated Primary Completion Date: December 30, 2020
• Estimated Study Completion Date: December 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sarilumab arm	Drug: Sarilumab; Treatment with Sarilumab 200 mg IV x 2 doses 24 hours apart for first 5 patients. If no severe AE and no significant improvement within 48 hours, the dose will be increased for subsequent patients to 400 mg IV for the first dose and 200 mg or 400 mg IV for the second dose 24 hours later. Te second dose will be decided at the investigators discretion.; Other Name: Kevzara®

Outcome Measures

Primary Outcome Measures :

1. Change in a severity rating on a 7-point ordinal scale [ Time Frame: 15 days ]
   Impact of sarilumab on the progression of COVID-19 associated respiratory failure. A significant improvement in a 7-point severity index is anticipated to occur with treatment with sarilumab.

Secondary Outcome Measures :

1. Percentage of patients reporting each severity rating on a 7-point severity ordinal scale [ Time Frame: 28 days ]
   Proportion of patients in each severity category at the end fo follow-up
2. Duration of mechanical ventilation [ Time Frame: 28 days ]
   Duration of mechanical ventilation measured by days of ventilation since treatment
3. Evaluate the safety of sarilumab in patients with severe pneumonia caused by COVID 19 [ Time Frame: 28 days ]

   All adverse events will be recorded in the CRF.

   Adverse Event is defined as any event that results in worsening of the health of the subject of the clinical trial, regardless of relationship to the experimental therapy. It can be any symptom, sign, illness or experience, including abnormal results of diagnostic procedures, that develops or worsens in severity during the course of the study.

   Serious Adverse Event are defined as any AE that is:

   • Fatal
   • Life-threatening*
   • Requires or prolongs hospital stay
   • Results in persistent or significant disability or incapacity
4. Number of ventilator free days in the first 28 days [ Time Frame: 28 days ]
   Number of ventilator free days in the first 28 days
5. Patients requiring mechanical ventilation [ Time Frame: 28 days ]
   Number and proportion of patients requiring mechanical ventilation
6. Change from baseline in PaO2/FiO2 in patients on mechanical ventilation [ Time Frame: since day of intubation until day of extubation or up to day 28 ]
   PaO2/FiO2 will be measured daily until extubation or day 28.
7. Time to improvement in oxygenation for at least 48 hours [ Time Frame: 28 days ]
   Increase in SpO2/FiO2 of 50 or more compared to nadir SpO2/FiO2
8. Time to saturation > 93.9% on room air [ Time Frame: 28 days ]
   Improvement on oxygenation using a threshold of SaO2 of 94% or better when breathing room air as a sign of improvement.
9. Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC - axilla; > 37.2ºC -oral; > 37.8 -rectal or tympanic) [ Time Frame: 28 days ]
   Resolution of fever.
10. Changes from baseline in white blood cell count if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Changes in white blood count on visits number 2, 3 ,4, 5 and 6.
11. Changes from baseline in hemoglobin levels if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Changes in hemoglobin on visits number 2, 3 ,4, 5 and 6.
12. Changes from baseline in platelet cell count if available on V2, V3, V4, V5, and V [ Time Frame: 28 days ]
    Changes in platelet counts on visits number 2, 3 ,4, 5 and 6.
13. Changes from baseline in D-Dimer leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Changes in D-dimer levels on visits number 2, 3 ,4, 5 and 6.
14. Number of deaths due to any cause [ Time Frame: 28 days ]
    All-cause mortality
15. Organ failure [ Time Frame: 28 days ]
    Events of organ failure after treatment: DIC, cardiac, hepatic, renal, cardiovascular
16. Changes from baseline in C Reactive protein if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of inflammation.
17. Changes from baseline in Ferritin leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of inflammation.
18. Changes from baseline in Troponin leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates potential myocardial involvement.
19. Changes from baseline in blood urea nitrogen leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of renal function
20. Changes from baseline in creatinine leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of renal function
21. Changes from baseline in blilirrubin leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of liver function
22. Changes from baseline in Aspartate transaminase (AST) leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of liver function
23. Changes from baseline in Alanine transaminase (ALT) leves if available on V2, V3, V4, V5, and V6 [ Time Frame: 28 days ]
    Indicates improvement or worsening of liver function

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. Written informed consent prior to performing study procedures. Oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible.

   In the case of a vital emergency without the possibility of prior consent, a patient may be included in the study if the recommendations of the legislation are followed (RD 1090/2015, article 7), as stated in section 10.3 of the protocol.

2. Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
3. Negative pregnancy test in case of fertile women*
4. Age >= 18
5. Infection by COVID-19 confirmed by rtPCR or other validated tests

6. Hospitalized (or documentation of a plan to admit to the hospital if the patient is in the emergency department) with illness of any duration, with evidence of pneumonia, and severe disease as defined by at least one of the following:

   1. High oxygen requirements (face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula)
   2. Lymphocytes < 0.8 x 109/L
   3. Serum ferritin > 300ng/mL
   4. Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching ≥ 1000 ng/mL.
   5. CPR > 10 mg/dL, or increasing over 24 hours

Exclusion Criteria:

Patients with any of the following exclusion criteria could not be included in the trial:

1. Hypersensitivity to the active substance or any of the excipients listed in section 6
2. Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days
3. Alkylating agents including cyclophosphamide (CYC) within 6 months of baseline
4. Cyclosporine (CsA), azathioprine (AZA) or mycophenolate mofetil (MMF) or leflunomide within 4 weeks of baseline.
5. Alkylating agents including cyclophosphamide (CYC) within 6 months of baseline
6. Tumor necrosis factor (TNF) inhibitors within 2-8 weeks (etanercept within 2 weeks, infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or after at least 5 half-lives have elapsed, whichever is longer.
7. Intravenous immunoglobulin (IVIG) within the past 5 months or plans to receive during the study period
8. Current use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day
9. Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents
10. Patients who have received immunosuppressive antibody therapy within the past 5 months, including intravenous immunoglobulin
11. AST/ALT values > 5 x normal.
12. Neutropenia (< 0.5 x 109/L).
13. Sever thrombocytopenia (< 50 x 109/L).
14. Sepsis caused by an alternative pathogen.
15. Diverticulitis with risk of perforation.
16. Ongoing infectious dermatitis.
17. Patients with another active infection, including localized infections.
18. Pregnant or breast-feeding females will be excluded
19. Positive serology for following infection: HIV, Hepatitis B, or C.

Contacts and Locations

Contacts

Contact: Javier J Zulueta, MD; +34948255400 ext 4772; jzulueta@unav.es

Contact: Gabriel Canel; +34948255400; gcanelc@unav.es

Locations

Spain

Clínica Universidad de Navarra, Universidad de Navarra; Recruiting

Pamplona, Navarra, Spain, 31008

Contact: Javier Zulueta, MD +34948255400 ext 4772 jzulueta@unav.es

Contact: Gabriel Canel +34948255400 gcanelc@unav.es

Principal Investigator: Javier J Zulueta, MD

Sub-Investigator: Luis M Seijo, MD

Sub-Investigator: Francisco Carmona, MD

Sub-Investigator: Marta Marín, MD

Sub-Investigator: Jose L del Pozo, MD

Sub-Investigator: Bruno Sangro, MD

Sub-Investigator: Marimar Ocon, RN

Hospital Universitario Infanta Leonor; Recruiting

Madrid, Spain, 28031

Contact: Jesus Troya, MD +341918297 jesus.troya@salud.madrid.org

Contact: Ismael Escobar, MD +341918297 ismael.escobar@salud.madrid.org

Principal Investigator: Jesus Troya, MD

Sponsors and Collaborators

Clinica Universidad de Navarra, Universidad de Navarra

Sanofi

Hospital Universitario Infanta Leonor

Investigators

• Principal Investigator: Javier J Zulueta, MD; Clinica Universidad de Navarra

More Information

• Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• ClinicalTrials.gov Identifier: NCT04661527
• Other Study ID Numbers: STRIKESARS-COV; 2020-001255-40 ( EudraCT Number )
• First Posted: December 10, 2020
• Last Update Posted: December 16, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Infection