A Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.

This study is multicenter, comparative, randomized, double-blind, placebo controlled clinical trial with adaptive design. Females and males, aged 18 years and older, admitted to hospital with severe COVID-19 pneumonia on SOC therapy will receive either levilimab 324 mg s/c or placebo s/c. In case of no clinical improvement is observed, investigator can administer a rescue therapy - open label LVL 324 mg s/c. The outcomes will be assessed up to day 60. Results of interim analysis of safety and efficacy data of first 60 enrolled subjects will be submitted for independent DMC review and decision about changes to the protocol.

Inclusion Criteria:

1. Signed informed consent (subject; legally authorized representative) or signed conclusion of panel of independent medical doctors

2. Males and non-pregnant females aged 18 years or older at the IC date

3. Positive test for SARS-CoV2 nucleic acid (RNA) at the IC date

4. Admitted as inpatient to a hospital with radiologically confirmed pneumonia

5. Severe form of COVID-19.

6. Subjects meeting any of the following criteria:

   • Total respiratory rate > 30 breaths per minute
   • SpO2 ≤ 93%
   • PaO2 /FiO2 ≤ 300 mmHg
   • Chest imaging (X-ray, CT, US) showed lesion progression within 24-48 hours >50%
   • Decrease of consciousness level, Psychomotor agitation/irritability
   • Hemodynamically unstable (systolic blood pressure <90 mmHg or diastolic blood pressure < 60 mmHg or urine output < 20 ml/h)
   • Arterial lactate > 2 mmol/l
   • qSOFA (quick sequential organ failure assessment score) > 2. Subjects meeting three following criteria: Low blood pressure (SBP ≤ 100 mmHg); High respiratory rate (≥ 22 breaths/min); Altered mentation (Glasgow Coma Scale ≤ 14)

Exclusion Criteria:

1. Critical COVID-19. Subjects meeting any of the following:

   • Respiratory failure and requiring invasive mechanical ventilation (tracheal intubation)
   • Septic shock
   • Multiple organ failure

2. Life expectancy < 24h, in the opinion of the investigator,

3. Unlikely to remain at the investigational site beyond 48 hours

4. Use of other monoclonal antibodies for COVID-19 treatment

5. Current treatment with immunosuppressive agents (including corticosteroids)

6. Participating in other drug clinical trials at the IC date or within 60 days after randomization (participation in COVID-19 anti-viral trials may be permitted if approved by Sponsor)

7. Laboratory values:

   • ALT / AST > 10 ULN at screening
   • Platelets < 50х109/l at screening
   • Absolute Neutrophil Count < 1х109/l at screening

8. Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)

9. Confirmed active tuberculosis

10. History of allergic reaction to monoclonal antibodies

11. Pregnancy or breastfeeding

12. Any illness or laboratory findings that, in the opinion of the study investigator, might pose an additional risk to the patient by their participation in the study,