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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: Levilimab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Kaluga, Russian Federation
    • State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"
  • Machačkala, Russian Federation
    • State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"
  • Moscow, Russian Federation
    • I.M. Sechenov First Moscow State Medical University (Sechenov University)
  • Moscow, Russian Federation
    • Pirogov Russian National Research Medical University
  • Moscow, Russian Federation
    • A.N. Bakulev National Medical Research Center of Cardiovascular Surgery
  • Moscow, Russian Federation
    • City Clinical Hospital No. 40 of the Department of Health of the city of Moscow
  • Moscow, Russian Federation
    • City Clinical Hospital No.52
  • Moscow, Russian Federation
    • City Clinical Hospital № 15 named. O.M. Filatov
  • Moscow, Russian Federation
    • City Clinical Hospital №1 named after N.I. Pirogov, Moscow City Health Department
  • Moscow, Russian Federation
    • Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation
  • Moscow, Russian Federation
    • Railway clinical hospital named after N.A. Semashko
  • Saint Petersburg, Russian Federation
    • Almazov National Medical Research Centre
  • Saint Petersburg, Russian Federation
    • Clinical Infectious Disease Hospital named after S.P. Botkin
  • Saint Petersburg, Russian Federation
    • North-Western State Medical University named after I.I.Mechnikov
  • Ufa, Russian Federation
    • Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
  • Vladikavkaz, Russian Federation
    • Federal State Budgetary Educational Institution of Higher Education "North Ossetian State Medical Academy" of the Ministry of Health of the Russian Federation (FSBEI HE SOGMA of the Ministry of Health of Russia)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LVL group; Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy	Drug: Levilimab; Levilimab 324 mg
PLACEBO_COMPARATOR: Placebo group; Single subcutaneous administration of placebo in combination with standard therapy	Drug: Placebo; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biocad

Publications and helpful links

General Publications

• Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA. The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study. Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 29, 2020
• Primary Completion (ACTUAL): July 3, 2020
• Study Completion (ACTUAL): August 3, 2020

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BCD-089-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No