The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.
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.
Drug: Levilimab
Levilimab 324 mg
Drug: Placebo
Placebo
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,
State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"
Kaluga, Russian Federation
State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"
Machačkala, 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
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, Russian Federation