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)

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.