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

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

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Levilimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent (subject; legally authorized representative) or signed conclusion of panel of independent medical doctors Males and non-pregnant females aged 18 years or older at the IC date Positive test for SARS-CoV2 nucleic acid (RNA) at the IC date Admitted as inpatient to a hospital with radiologically confirmed pneumonia Severe form of COVID-19. 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: Critical COVID-19. Subjects meeting any of the following: Respiratory failure and requiring invasive mechanical ventilation (tracheal intubation) Septic shock Multiple organ failure Life expectancy < 24h, in the opinion of the investigator, Unlikely to remain at the investigational site beyond 48 hours Use of other monoclonal antibodies for COVID-19 treatment Current treatment with immunosuppressive agents (including corticosteroids) 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) Laboratory values: ALT / AST > 10 ULN at screening Platelets < 50х109/l at screening Absolute Neutrophil Count < 1х109/l at screening Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) Confirmed active tuberculosis History of allergic reaction to monoclonal antibodies Pregnancy or breastfeeding 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,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LVL group<br>Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy | Drug: Levilimab<br>* Levilimab 324 mg<br>|
| Placebo Comparator: Placebo group<br>Single subcutaneous administration of placebo in combination with standard therapy | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with sustained clinical recovery | Sustained clinical recovery is defined as either an improvement of at least 2 categories relative to baseline on a 7-Category Ordinal Scale of Clinical Status or reaching categories Discharged / Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care at day 14. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status | 7-Category Ordinal Scale of Clinical Status: Not hospitalized / Discharged Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, requiring non-invasive ventilation or high flow oxygen devices Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Death | Day 30 | 
| Proportion of patients transferred to the ICU |  | Day 60 | 
| Duration of fever |  | Day 60 | 
| Duration of hospitalization |  | Day 60 | 
| Change in ESR |  | Day 30 | 
| Change in serum CRP level |  | Day 30 | 
| Change in serum IL-6 level |  | Day 30 |