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

Phase 3

Completed

• Conditions: COVID-19
• Interventions: Drug: Placebo; Drug: Levilimab

• Registration Number: NCT04397562
• Lead Sponsor: Biocad

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.

Study Timeline

• Study Start: 2020-04-29
• Study First Submitted: 2020-05-19
• Study First Submitted QC: 2020-05-20
• Study First Posted: 2020-05-21
• Primary Completion: 2020-07-03
• Study Completion: 2020-08-03
• Status Verified: 2020-11
• Last Update Submitted: 2021-11-15
• Last Update Posted: 2021-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 206

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	Single subcutaneous administration of placebo in combination with standard therapy
LVL group	Levilimab	Single subcutaneous administration of levilimab at a dose of 324 mg in combination with standard therapy

Primary Outcome Measures

Name	Time	Method
Proportion of patients with sustained clinical recovery	Day 14	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

Name	Time	Method
Proportion of patients transferred to the ICU	Day 60
Duration of hospitalization	Day 60
Change in ESR	Day 30
Change in serum IL-6 level	Day 30
Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status	Day 30	7-Category Ordinal Scale of Clinical Status: 1. Not hospitalized / Discharged; 2. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 3. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7. Death
Duration of fever	Day 60
Change in serum CRP level	Day 30

Trial Locations

Locations (16)

Clinical Infectious Disease Hospital named after S.P. Botkin; 🇷🇺 Saint Petersburg, 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

State Budget Institution of the Republic of Dagestan "Republican Clinical Hospital"; 🇷🇺 Machačkala, Russian Federation

North-western State Medical University named after I.I.Mechnikov; 🇷🇺 Saint Petersburg, Russian Federation

Pirogov Russian National Research Medical University; 🇷🇺 Moscow, Russian Federation

Railway clinical hospital named after N.A. Semashko; 🇷🇺 Moscow, Russian Federation

City Clinical Hospital № 15 named. O.M. Filatov; 🇷🇺 Moscow, Russian Federation

Federal State Budgetary Institution "Central Clinical Hospital with Clinic", Office of the President of the Russian Federation; 🇷🇺 Moscow, Russian Federation

City Clinical Hospital No. 40 of the Department of Health of the city of Moscow; 🇷🇺 Moscow, 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

City Clinical Hospital No.52; 🇷🇺 Moscow, Russian Federation

State Budgetary Healthcare Institution Kaluga region "Kaluga Regional Clinical Hospital"; 🇷🇺 Kaluga, Russian Federation

A.N. Bakulev National Medical Research Center of Cardiovascular Surgery; 🇷🇺 Moscow, Russian Federation

Almazov National Medical Research Centre; 🇷🇺 Saint Petersburg, Russian Federation

City Clinical Hospital №1 named after N.I. Pirogov, Moscow City Health Department; 🇷🇺 Moscow, Russian Federation

I.M. Sechenov First Moscow State Medical University (Sechenov University); 🇷🇺 Moscow, Russian Federation