Back to resultsA Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19 (CORONA)
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Levilimab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
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,
Sites / Locations
- State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"
- State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"
- A.N. Bakulev National Medical Research Center of Cardiovascular Surgery
- City Clinical Hospital No. 40 of the Department of Health of the city of Moscow
- City Clinical Hospital No.52
- City Clinical Hospital № 15 named. O.M. Filatov
- City Clinical Hospital №1 named after N.I. Pirogov, Moscow City Health Department
- Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
- Pirogov Russian National Research Medical University
- Railway clinical hospital named after N.A. Semashko
- Almazov National Medical Research Centre
- Clinical Infectious Disease Hospital named after S.P. Botkin
- North-western State Medical University named after I.I.Mechnikov
- Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the 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)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LVL group
Placebo group
Arm Description
Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy
Single subcutaneous administration of placebo in combination with standard therapy
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Proportion of patients transferred to the ICU
Duration of fever
Duration of hospitalization
Change in ESR
Change in serum CRP level
Change in serum IL-6 level
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04397562
Brief Title
A Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19
Acronym
CORONA
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
April 29, 2020 (Actual)
Primary Completion Date
July 3, 2020 (Actual)
Study Completion Date
August 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
206 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LVL group
Arm Type
Experimental
Arm Description
Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Single subcutaneous administration of placebo in combination with standard therapy
Intervention Type
Drug
Intervention Name(s)
Levilimab
Intervention Description
Levilimab 324 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Proportion of patients with sustained clinical recovery
Description
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.
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status
Description
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
Time Frame
Day 30
Title
Proportion of patients transferred to the ICU
Time Frame
Day 60
Title
Duration of fever
Time Frame
Day 60
Title
Duration of hospitalization
Time Frame
Day 60
Title
Change in ESR
Time Frame
Day 30
Title
Change in serum CRP level
Time Frame
Day 30
Title
Change in serum IL-6 level
Time Frame
Day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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,
Facility Information:
Facility Name
State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"
City
Kaluga
Country
Russian Federation
Facility Name
State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"
City
Machačkala
Country
Russian Federation
Facility Name
A.N. Bakulev National Medical Research Center of Cardiovascular Surgery
City
Moscow
Country
Russian Federation
Facility Name
City Clinical Hospital No. 40 of the Department of Health of the city of Moscow
City
Moscow
Country
Russian Federation
Facility Name
City Clinical Hospital No.52
City
Moscow
Country
Russian Federation
Facility Name
City Clinical Hospital № 15 named. O.M. Filatov
City
Moscow
Country
Russian Federation
Facility Name
City Clinical Hospital №1 named after N.I. Pirogov, Moscow City Health Department
City
Moscow
Country
Russian Federation
Facility Name
Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation
City
Moscow
Country
Russian Federation
Facility Name
I.M. Sechenov First Moscow State Medical University (Sechenov University)
City
Moscow
Country
Russian Federation
Facility Name
Pirogov Russian National Research Medical University
City
Moscow
Country
Russian Federation
Facility Name
Railway clinical hospital named after N.A. Semashko
City
Moscow
Country
Russian Federation
Facility Name
Almazov National Medical Research Centre
City
Saint Petersburg
Country
Russian Federation
Facility Name
Clinical Infectious Disease Hospital named after S.P. Botkin
City
Saint Petersburg
Country
Russian Federation
Facility Name
North-western State Medical University named after I.I.Mechnikov
City
Saint Petersburg
Country
Russian Federation
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
City
Ufa
Country
Russian Federation
Facility Name
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)
City
Vladikavkaz
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34586459
Citation
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.
Results Reference
background
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/34586459/
Description
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A Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19
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