Randomized Study of Efficacy of Different Treatment Regimens of Olokizumab

• Status: Recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to evaluate the efficacy and safety of Artlegia (INN:

olokizumab) new dosing regimen in patients with moderate coronavirus infection (COVID-19) with signs of hyperinflammation.

This study is a multicentre, open-label, randomized, comparative, parallel group, active-controlled clinical trial.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm
• Collaborators: Federal Budget Institution of Science "Central Research Institute of Epidemiology" of the Rospotrebnadzor; Group of companies Medsi, JSС

Criteria

Inclusion Criteria:

1. Signed Informed Consent for participation in this study.

2. Hospitalization (no more than 72 hours prior to randomization) with a diagnosis of coronavirus infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (COVID-19).

3. Moderate COVID-19. Moderate course of the disease is characterized by pneumonia on chest computed tomography (CT) (CT-1,2 stages) and body temperature > 38 °C, in combination with 1 or more of the following:

• SpO2 <95%,

• respiratory rate > 22,

• dyspnea on exertion,

• C-reactive protein (CRP) level> 10 mg / l,

• one of the following risk factors: diabetes mellitus, severe cardiovascular disease, chronic renal failure, cancer, obesity, or age ≥ 65 years.

4. The presence of signs of hyperinflammation. Signs of hyperinflammation are body temperature ≥ 38 °C for 2 days or more, combined with 1 or more of the following:

• CRP level > 3 Upper Normal Limit (UNL),

• White blood cell count - 2.0-3.5 × 10^9 / l,

• Absolute lymphocyte count - 1.0-1.5 × 10^9 / l

5. Infection caused by the SARS-CoV-2 confirmed by of Polymerase chain reaction (PCR) test or an express test for antigen / antibodies to SARS-CoV-2 framework of the protocol).

6. Ability to follow protocol requirements and perform all clinical trial procedures.

7. The willingness of the participants and their sexual partners to use reliable methods of contraception, during the entire study and at least 3 months after the treatment completion. This requirement does not apply to participants who have undergone surgical sterilization as well as to women with permanent cessation of menstruation, which should be determined retrospectively after 12 months of natural amenorrhea, i.e. amenorrhea with an appropriate clinical status (eg, appropriate age). Reliable methods of contraception involve the use of one barrier method in combination with one of the following: spermicides, intrauterine spiral/oral contraceptives in a sexual partner.

8. Willingness not to drink alcohol during the entire study.

Additional inclusion criteria for the pharmacokinetics (PK) subgroup:

1. Signed informed consent to participate in the additional study of pharmacokinetics.

2. Body mass index 18.5 - 35.0 kg/m2.

3. The ability of the patient, by the opinion of the investigator, to participate in the additional study of pharmacokinetics and to provide the required number of blood samples.

Exclusion Criteria:

1. Hypersensitivity to olokizumab and / or other components of the study drug.

2. Contraindications to favipiravir or glucocorticosteroids or Janus kinase inhibitors (baricitinib).

3. Signs of a severe or extremely severe course of COVID-19, such as:

• altered level of consciousness, agitation,

• the need for / use of Non-invasive ventilation (NIV) / Adaptive lung ventilation (ALV) / Extracorporeal membrane oxygenation (ECMO) at screening,

• hemodynamic instability eg systolic blood pressure < 90 mm Hg or diastolic blood pressure < 60 mm Hg and urine output less than 20 ml / hour,

• CT-3,4 stage on chest CT, signs of Acute respiratory distress syndrome (ARDS),

• arterial blood lactate > 2 mmol / l,

• quick Sequential Organ Failure Assessment (qSOFA) > 2 points.

4. Any of the following laboratory abnormalities:

• Hemoglobin <80 g / l,

• Absolute neutrophil count <0.5 x 10^9 / l,

• White blood cell count <2.0 x 10^9 / l,

• Platelet count <50 x 10^9 / l,

• Alanine transaminase (ALT) and / or Aspartate aminotransferase (AST) ≥ 3.0 x UNL.

5. Severe renal failure: creatinine clearance < 30 ml / min.

6. Confirmed sepsis with non-COVID-19 pathogens and procalcitonin levels > 0.5 ng / ml.

7. Prior hepatitis B and / or C virus infection.

8. High probability of disease progression to death within the next 24 hours, regardless of therapy, by the opinion of the investigator.

9. Concomitant diseases associated with a poor prognosis.

10. Immunosuppressive therapy for organ transplantation.

11. Recent (less than 5 half-lives) or prescribed at screening:

• Olokizumab (use or prescription prior to study randomization);

• Biological drugs with immunosuppressive effects, including, but not limited to:Interleukin 1 (IL-1) inhibitors (anakinra, canakinumab), IL-6 receptor inhibitors (tocilizumab, sarilumab, levilimab), IL-17 (secukinumab, netakimab), tumor necrosis factor α inhibitors (TNFα) (infliximab, adalimumab, etanercept, etc.), anti-B-cell drugs, and others;

• Immunosuppressive drugs (including, but not limited to):

• glucocorticoids in high doses (> 1 mg / kg prednisolone equivalent) orally or parenterally;

• Janus kinase (JAK) kinase inhibitors;

• cyclophosphamide, etc.

12. History of active tuberculosis or suspected active tuberculosis.

13. Simultaneous participation in another clinical trial.

14. Pregnancy or breastfeeding at screening; planning pregnancy during the entire study and within 3 months after the completion of treatment.

15. Any information from anamnesis that may lead to a complicated interpretation of the study results or create additional risk for the patient as a result of participation in the study.

16. Known (from history) or suspected abuse of alcohol, psychotropic drugs; drug addiction.

17. Subjects with a history or presence of any psychiatric disorder(s).