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

NCT ID: NCT04661527

Last Updated: 2020-12-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-22
• Study Completion Date: 2020-12-30

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).

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.

Conditions

COVID-19 Drug Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sarilumab arm

Group Type: EXPERIMENTAL

Sarilumab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Kevzara®

Eligibility 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Hospital Universitario Infanta Leonor

OTHER

Sponsor Role: collaborator

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier J Zulueta, MD

Role: PRINCIPAL_INVESTIGATOR

Clinica Universidad de Navarra

Locations

Clínica Universidad de Navarra, Universidad de Navarra

Pamplona, Navarre, Spain

Site Status: RECRUITING

Hospital Universitario Infanta Leonor

Madrid, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Javier J Zulueta, MD

Role: CONTACT

Phone: +34948255400

Email: jzulueta@unav.es

Gabriel Canel

Role: CONTACT

Phone: +34948255400

Email: gcanelc@unav.es

Facility Contacts

Javier Zulueta, MD

Role: primary

Gabriel Canel

Role: backup

Jesus Troya, MD

Role: primary

Ismael Escobar, MD

Role: backup

Other Identifiers

2020-001255-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

STRIKESARS-COV

Identifier Type: -

Identifier Source: org_study_id