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

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).

Study Overview

• Status: Unknown
• Conditions: COVID-19 Drug Treatment
• Intervention / Treatment: Drug: Sarilumab

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28031
    • Recruiting
    • Hospital Universitario Infanta Leonor
    • Contact: Jesus Troya, MD; Phone Number: +341918297; Email: jesus.troya@salud.madrid.org
    • Contact: Ismael Escobar, MD; Phone Number: +341918297; Email: ismael.escobar@salud.madrid.org
    • Principal Investigator: Jesus Troya, MD
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra, Universidad de Navarra
      • Contact: Gabriel Canel; Phone Number: +34948255400; Email: gcanelc@unav.es
      • Contact: Javier Zulueta, MD; Phone Number: 4772 +34948255400; Email: jzulueta@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

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Kevzara®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in a severity rating on a 7-point ordinal scale	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.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients reporting each severity rating on a 7-point severity ordinal scale	Proportion of patients in each severity category at the end fo follow-up	28 days
Duration of mechanical ventilation	Duration of mechanical ventilation measured by days of ventilation since treatment	28 days
Evaluate the safety of sarilumab in patients with severe pneumonia caused by COVID 19	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	28 days
Number of ventilator free days in the first 28 days	Number of ventilator free days in the first 28 days	28 days
Patients requiring mechanical ventilation	Number and proportion of patients requiring mechanical ventilation	28 days
Change from baseline in PaO2/FiO2 in patients on mechanical ventilation	PaO2/FiO2 will be measured daily until extubation or day 28.	since day of intubation until day of extubation or up to day 28
Time to improvement in oxygenation for at least 48 hours	Increase in SpO2/FiO2 of 50 or more compared to nadir SpO2/FiO2	28 days
Time to saturation > 93.9% on room air	Improvement on oxygenation using a threshold of SaO2 of 94% or better when breathing room air as a sign of improvement.	28 days
Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC - axilla; > 37.2ºC -oral; > 37.8 -rectal or tympanic)	Resolution of fever.	28 days
Changes from baseline in white blood cell count if available on V2, V3, V4, V5, and V6	Changes in white blood count on visits number 2, 3 ,4, 5 and 6.	28 days
Changes from baseline in hemoglobin levels if available on V2, V3, V4, V5, and V6	Changes in hemoglobin on visits number 2, 3 ,4, 5 and 6.	28 days
Changes from baseline in platelet cell count if available on V2, V3, V4, V5, and V	Changes in platelet counts on visits number 2, 3 ,4, 5 and 6.	28 days
Changes from baseline in D-Dimer leves if available on V2, V3, V4, V5, and V6	Changes in D-dimer levels on visits number 2, 3 ,4, 5 and 6.	28 days
Number of deaths due to any cause	All-cause mortality	28 days
Organ failure	Events of organ failure after treatment: DIC, cardiac, hepatic, renal, cardiovascular	28 days
Changes from baseline in C Reactive protein if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of inflammation.	28 days
Changes from baseline in Ferritin leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of inflammation.	28 days
Changes from baseline in Troponin leves if available on V2, V3, V4, V5, and V6	Indicates potential myocardial involvement.	28 days
Changes from baseline in blood urea nitrogen leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of renal function	28 days
Changes from baseline in creatinine leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of renal function	28 days
Changes from baseline in blilirrubin leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of liver function	28 days
Changes from baseline in Aspartate transaminase (AST) leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of liver function	28 days
Changes from baseline in Alanine transaminase (ALT) leves if available on V2, V3, V4, V5, and V6	Indicates improvement or worsening of liver function	28 days

Collaborators and Investigators

• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborators: Sanofi; Hospital Universitario Infanta Leonor
• Investigators: Principal Investigator: Javier J Zulueta, MD, Clinica Universidad de Navarra

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2020
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Shock; COVID-19; Cytokine Release Syndrome
• Other Study ID Numbers: STRIKESARS-COV; 2020-001255-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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