Severe pneumonia caused by infection with SARS CoV 2. MedDRA version: 20.0 Level: LLT Classification code 10051905 Term: Coronavirus infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Kevzara
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: SARILUMAB
CAS Number: 1189541-98-7
Sponsors
Clínica Universidad de Navarra/Universidad de Navarra
Eligibility
Sex/Gender
All
Inclusion 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. Greater than or equal to 18 years old 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: a. High oxygen requirements (face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula) b. Lymphocytes 300ng/mL d. Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching = 1000 ng/mL. e. CPR > 10 mg/dL, or increasing over 24 hours * A woman is considered fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity to the active substance or any of the excipients listed in section 6 of the protocol 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 1. Assess the impact of sarilumab on markers of systemic inflammation and the coagulation cascade in the context of COVID-19. 2. Assess the impact of sarilumab on mortality caused by COVID-19. 3. Assess the impact of sarilumab on oxygenation. 4. Evaluate the safety of sarilumab in patients with severe pneumonia caused by COVID 19.;Primary end point(s): - Change in a severity rating on a 7-point ordinal scale 7-point Ordinal Scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care 7. Not hospitalized;Timepoint(s) of evaluation of this end point: Time Frame: day 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of patients reporting each severity rating on a 7-point severity ordinal scale (time frame: day 28) - Duration of mechanical ventilation measured by days of ventilation since treatment (time frame: up to day 28) - Number of ventilator free days in the first 28 days (time frame: baseline to day 28) - Number of patients requiring mechanical ventilation (time frame: up to day 28) - Number of patients admitted to the ICU (time frame: up to day 28) - 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) - Time to improvement in oxygenation for at least 48 hours (time frame: up to day 28) o Increase in SpO2/FiO2 of 50 or more compared to nadir SpO2/FiO2 - Time to saturation > 93.9% on room air (time frame: up to day 30) - Number of days with supplemental oxygen (time frame: up to day 30) - 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: up to day 30) - Changes from baseline in inflammatory parameters and other laboratory tests available on V2, V3, V4, V5, and V6: CRP, LDH, Ferritin, Troponin, BUN, creatinine, AST/ALT, bilirrubin (time frame: up to day 28) - Changes from baseline in white blood cell count if available on V2, V3, V4, V5, and V6 (time frame: up to 28 days or discharge) - Changes from baseline in hemoglobin levels if available on V2, V3, V4, V5, and V6 (time frame: up to 28 days or discharge) - Changes from baseline in platelet cell count if available on V2, V3, V4, V5, and V6 (time frame: up to 28 days or discharge) - Changes from baseline in D-Dimer leves if available on V2, V3, V4, V5, and V6 (time frame: up to 28 days or discharge) - Number of deaths due to any cause (time frame: up to day 28) - Organ failure (DIC, cardiac, hepatic, renal, cardiovascular) (time frame: up to day 28);Timepoint(s) of evaluatio | — |
Countries
Spain
Contacts
Public ContactUCEC
Clínica Universidad de Navarra
Outcome results
None listed