Clinical trial NCT04661527: Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19
Official title: Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19 Drug Treatment
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Hospital Universitario Infanta Leonor
First posted: 2020-12-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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)
Primary purpose: TREATMENT

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.

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:

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.

Primary outcomes:
measure: Change in a severity rating on a 7-point ordinal scale
timeFrame: 15 days
Secondary outcomes:
measure: Percentage of patients reporting each severity rating on a 7-point severity ordinal scale
timeFrame: 28 days
measure: Duration of mechanical ventilation
timeFrame: 28 days
measure: Evaluate the safety of sarilumab in patients with severe pneumonia caused by COVID 19
timeFrame: 28 days
measure: Number of ventilator free days in the first 28 days
timeFrame: 28 days
measure: Patients requiring mechanical ventilation
timeFrame: 28 days
measure: Change from baseline in PaO2/FiO2 in patients on mechanical ventilation
timeFrame: since day of intubation until day of extubation or up to day 28
measure: Time to improvement in oxygenation for at least 48 hours
timeFrame: 28 days
measure: Time to saturation > 93.9% on room air
timeFrame: 28 days
measure: Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC - axilla; > 37.2ºC -oral; > 37.8 -rectal or tympanic)
timeFrame: 28 days
measure: Changes from baseline in white blood cell count if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in hemoglobin levels if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in platelet cell count if available on V2, V3, V4, V5, and V
timeFrame: 28 days
measure: Changes from baseline in D-Dimer leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Number of deaths due to any cause
timeFrame: 28 days
measure: Organ failure
timeFrame: 28 days
measure: Changes from baseline in C Reactive protein if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in Ferritin leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in Troponin leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in blood urea nitrogen leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in creatinine leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in blilirrubin leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in Aspartate transaminase (AST) leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
measure: Changes from baseline in Alanine transaminase (ALT) leves if available on V2, V3, V4, V5, and V6
timeFrame: 28 days
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra, Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
Study officials:
affiliation: Clinica Universidad de Navarra
name: Javier J Zulueta, MD
role: PRINCIPAL_INVESTIGATOR
References: