Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19)

This is an interventional treatment trial for COVID-19 focused on measuring SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, 2019-nCoV, 2019 novel coronavirus, Respiratory disease, lung disease, COVID-19, coronavirus Read More

Inclusion criteria:

1. The presence of a voluntarily signed and dated Patient Informed Consent Form for participation in this study, or a record of an Medical Consilium decision justifying patient's participation in case of patient is unable to state his/her will.

2. Having either of the following COVID-associated respiratory syndromes:

   • pneumonia with oxygenation saturation SpO2 ≤93% (on room air) or respiratory rate greater than 30/min;
   • Acute respiratory distress syndrome (ARDS) ( PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315 if PaO2 is not available).

3. COVID-19 diagnosis based on:

   • laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction method (PCR).

OR

• Bilateral changes in the lungs typical for COVID-19, based on chest computed tomography results.

Exclusion criteria:

1. A history of hypersensitivity to the study drugs (RPH-104 and/or OKZ), and/or their components.

2. The presence of any of the following laboratory abnormalities:

   • absolute neutrophil counts < 0.5 x 10^9 L
   • white blood cell count < 2 x 10^9 L
   • platelet count <50 x 10^9 L
   • Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) ≥ 3.0 x Upper Limit of Normal (ULN)
3. Severe renal failure: creatinine clearance < 30 mL/min
4. Septic shock (vasopressors are required to maintain mean arterial pressure ≥ 65 mm Hg and lactate ≥ 2 mmol/L in the absence of hypovolemia)
5. The disease progresses to death over the next 24 hours, regardless of treatment, according to Investigator.
6. Perforation of the gastrointestinal tract, a history of diverticulitis.
7. Administration of plasma from COVID-19 convalescent donors within 4 weeks before study enrollment and/or planned administration during the study.
8. Recent (less then 5 half-lives) administration of tocilizumab or sarilumab;

9. Recent (less then 5 half-lives) or planned during the current study period use of the following drugs:

   • biologics (except RPH-104 or OKZ) with immunosuppressive effect, including, but not limited to: Interleukin-1 (IL-1) inhibitors (anakinra, rilonacept, canakinumab), IL- 6 inhibitors (except tocilizumab and sarilumab), IL-17A inhibitors (secukinumab), tumor necrosis factor α (TNFα) inhibitors (infliximab, adalimumab, etanercept, etc.), antiB-cell drugs, etc.

   • other immunosuppressive drugs (with the exception of methotrexate in a dose of up to 25 mg/week), including, but not limited to:

     1. high doses of glucocorticoids (equivalent to prednisolone > 1 mg/kg) orally or parenterally;
     2. Janus kinase (JAK) kinase inhibitors; cyclophosphamide, etc.
10. Concurrent participation in another clinical trial.
11. Pregnancy, breastfeeding.
12. A history of active tuberculosis, or active tuberculosis suspected by the Investigator.