Clinical trial NCT04397562: A Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2020-05-21
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Proportion of patients with sustained clinical recovery
timeFrame: Day 14
Secondary outcomes:
measure: Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status
timeFrame: Day 30
measure: Proportion of patients transferred to the ICU
timeFrame: Day 60
measure: Duration of fever
timeFrame: Day 60
measure: Duration of hospitalization
timeFrame: Day 60
measure: Change in ESR
timeFrame: Day 30
measure: Change in serum CRP level
timeFrame: Day 30
measure: Change in serum IL-6 level
timeFrame: Day 30
Other outcomes:
Locations:
city: Kaluga
country: Russian Federation
facility: State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"
city: Machačkala
country: Russian Federation
facility: State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"
city: Moscow
country: Russian Federation
facility: A.N. Bakulev National Medical Research Center of Cardiovascular Surgery
city: Moscow
country: Russian Federation
facility: City Clinical Hospital No. 40 of the Department of Health of the city of Moscow
city: Moscow
country: Russian Federation
facility: City Clinical Hospital No.52
city: Moscow
country: Russian Federation
facility: City Clinical Hospital № 15 named. O.M. Filatov
city: Moscow
country: Russian Federation
facility: City Clinical Hospital №1 named after N.I. Pirogov, Moscow City Health Department
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University (Sechenov University)
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Moscow
country: Russian Federation
facility: Railway clinical hospital named after N.A. Semashko
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Saint Petersburg
country: Russian Federation
facility: Clinical Infectious Disease Hospital named after S.P. Botkin
city: Saint Petersburg
country: Russian Federation
facility: North-western State Medical University named after I.I.Mechnikov
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
city: Vladikavkaz
country: Russian Federation
facility: 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)
Study officials:
References:
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.