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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04397562
• Other study ID #: BCD-089-4
• Status: Completed
• Phase: Phase 3
• Start date: April 29, 2020
• Est. completion date: August 3, 2020

Study information

• Verified date: November 2020
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: August 3, 2020
• Est. primary completion date: July 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 < 50?109/l at screening
• Absolute Neutrophil Count < 1?109/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,

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Levilimab
Levilimab 324 mg
• Placebo
Placebo

Locations

Country	Name	City	State
Russian Federation	State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"	Kaluga
Russian Federation	State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"	Machackala
Russian Federation	A.N. Bakulev National Medical Research Center of Cardiovascular Surgery	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	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	Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation	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	Railway clinical hospital named after N.A. Semashko	Moscow
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	Saint Petersburg
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation	Ufa
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)	Vladikavkaz

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Proportion of patients transferred to the ICU		Day 60
Secondary	Duration of fever		Day 60
Secondary	Duration of hospitalization		Day 60
Secondary	Change in ESR		Day 30
Secondary	Change in serum CRP level		Day 30
Secondary	Change in serum IL-6 level		Day 30

External Links

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