COVID-19 Clinical Trial
— RESETOfficial title:
A Multicenter, Open-label, Randomized Study of the Efficacy and Safety of Artlegia (INN: Olokizumab) New Dosing Regimen in Patients With Coronavirus Infection (COVID-19) With Signs of Hyperinflammation
Verified date | February 2023 |
Source | R-Pharm |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 198 |
Est. completion date | April 2023 |
Est. primary completion date | October 31, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 (with the exception of those listed in inclusion criteria No. 3: diabetes mellitus, severe cardiovascular disease, chronic renal failure, cancer, obesity, or age = 65 years). 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 a inhibitors (TNFa) (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). |
Country | Name | City | State |
---|---|---|---|
Russian Federation | Federal State Budgetary Institution "Central Clinical Hospital with a Polyclinic" of Presidential Administration of the Russian Federation | Moscow | |
Russian Federation | State Budgetary Healthcare Institution "City Clinical Hospital ? 52 of Moscow Healthcare Department" | Moscow | |
Russian Federation | State Budgetary Healthcare Institution "City Clinical Hospital named after F.I. Inozemtsev of Moscow Healthcare Department" | Moscow | |
Russian Federation | State Budgetary Healthcare Institution "Infectious Diseases Hospital No. 1 of Moscow Healthcare Department" | Moscow | |
Russian Federation | State Budgetary healthcare Institution of the Voronezh region "Voronezh Regional Clinical Hospital No. 1" | Voronezh |
Lead Sponsor | Collaborator |
---|---|
R-Pharm | Federal Budget Institution of Science "Central Research Institute of Epidemiology" of the Rospotrebnadzor, Group of companies Medsi, JS? |
Russian Federation,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Rate of clinical deterioration by at least 1 point from the baseline ordinal score at day 7, depending on study group | Rate of clinical deterioration by at least 1 point from the baseline ordinal score at day 7, depending on study group | Up to day 7 | |
Other | Clinical recovery rate at day 14 | Clinical recovery defined as score of 3 or less on a 10-point ordinal scale of clinical improvement, 14 days are counted from the day of the first administration / intake of study / comparison therapy by treatment group | Up to day 14 | |
Other | Cumulative incidence of transfer to intensive care unit (ICU), transfer to mechanical ventilation, development of ARDS and / or death, at day 28 | Cumulative incidence of transfer to ICU, transfer to mechanical ventilation, development of ARDS and / or death, at day 28 | Uo to day 28 | |
Other | Incidence of progression on chest CT at day 28 | Incidence of progression on chest CT at day 28, depending on study group | Up to day 28 | |
Other | Rate of transfer to ICU at day 28 | Rate of transfer to ICU at day 28, depending on study group | Up to day 28 | |
Other | Rate of transfer to mechanical ventilation at day 28 | Rate of transfer to mechanical ventilation at day 28, depending on study group | Up to day 28 | |
Other | Incidence of ARDS at day 28 | Incidence of ARDS at day 28, depending on study group | Up to day 28 | |
Other | Incidence of death from any cause at day 28 | Incidence of death from any cause at day 28, depending on study group | Up to day 28 | |
Other | Incidence of symptoms of a secondary bacterial infection | leukocytosis > 12x10^9 / l (in the absence of previous use of glucocorticosteroids), and / or shift to stab > 10 %, and / or purulent sputum or other clinical manifestations of purulent inflammation, and / or an increase in procalcitonin> 0.5 ng / ml depending on study group |
Up to day 28 | |
Other | Time to improvement in clinical status by at least 1 point | Time to improvement in clinical status by at least 1 point (from the moment of drug administration) (median, in days), depending on study group | from the moment of drug administration to improvement, up to 28 days | |
Other | Incidence of improvement in clinical status by at least 1 point on days 3, 5, 7, 10, 14, 21, 28, depending on study group | Incidence of improvement in clinical status by at least 1 point on days 3, 5, 7, 10, 14, 21, 28, depending on study group | Up to day 28 | |
Other | Time to reach SpO2 = 95%, without oxygen support for 2 consecutive days | Time to reach SpO2 = 95%, without oxygen support for 2 consecutive days (from the moment of drug administration) (median, in days), depending on study group | from the moment of drug administration to the moment when SpO2 = 95%, up to 28 days | |
Other | Duration of hospitalization at day 28 | Duration of hospitalization at day 28 (from the moment of drug administration) (median, in days), depending on study group | from the moment of drug administration to discharge, up to 28 days | |
Other | Duration of ICU stay at day 28 | Duration of ICU stay at day 28 (from the moment of drug administration) (median, in days), depending on study group | from the moment of drug administration to discharge from ICU, up to 28 days | |
Other | Time to normalization of temperature | Time to normalization of temperature (body temperature less than 37 °C for 48 hours or more, without taking antipyretics) (from the moment of drug administration) (median, in days), depending on study group | from the moment of drug administration to temperature normalization, up to 28 days | |
Other | Change from baseline of the assessment of the immune status by the Investigator | Change from baseline of the assessment of the immune status by the Investigator, based on clinical course and laboratory markers (- IL-6, - complement components - C3 and C4, T-lymphocytes (CD3 + CD19-); T - helpers (CD3 + CD4 + ); T - cytotoxic lymphocytes (CD3 + CD8); Immunoregulatory index (T-helpers / T-cytotoxic), (CD3 + CD4 + / CD3 + CD8 +); B - lymphocytes (CD3-CD19 +); Activated T-lymphocytes with phenotype (CD3 + HLA-DR +); Lymphocytes with HLA-DR + phenotype, NK cells total (CD3- CD16 + CD56 +); Activated T-cells with markers of NK cells (CD3 + CD56 +). | Baseline, day 28 | |
Primary | Clinical recovery rate at day 7 | Clinical recovery defined as score of 3 or less on a 10-point ordinal scale of clinical improvement. (From 0 "Healthy - no clinical manifestations, no viral RNA detected" to 10 "Death".) 7 days are counted from the day of the first administration / intake of study therapy / comparison therapy, depending on study group. Criteria for transition from category "4" to category "3" (criteria for potential discharge): body temperature < 37 °C; respiratory rate = 20 per minute; SpO2 = 95% without oxygen support, CRP < 10 mg/l. If any emergency procedures should be prescribed and/or signs of progression on CT are detected, the patient cannot be discharged/transferred to category "3". (In the case of the "rescue" therapy use or the development of clinical deterioration (an increase in the score by 1 point or more) during the follow-up period in a previously recovered patient, the patient is not considered as a "responder", i.e., who has reached the primary endpoint.) |
Up to day 7 | |
Secondary | Rate of clinical deterioration by at least 1 point from the baseline ordinal score at day 28, depending on study group | Rate of clinical deterioration by at least 1 point from the baseline ordinal score at day 28, depending on study group | Up to day 28 | |
Secondary | CRP normalization rate | Normalization is defined as CRP blood level within normal range (< 10 mg/l), assessed on days 5, 10, 14, 28, depending on study group. | Up to Day 28 | |
Secondary | Ferritin normalization rate | Normalization is defined as ferritin blood level within normal range, assessed on days 5, 10, 14, 28, depending on study group. | Up to Day 28 | |
Secondary | D-dimer normalization rate | Normalization is defined as D-dimer blood level within normal range, assessed on days 5, 10, 14, 28, depending on study group. | Up to Day 28 | |
Secondary | Mean CRP levels | Mean CRP levels assessed on days 5, 10, 14, 28, depending on study group | Up to Day 28 | |
Secondary | Mean ferritin levels | Mean ferritin levels assessed on days 5, 10, 14, 28, depending on study group | Up to Day 28 | |
Secondary | Mean D-dimer levels | Mean D-dimer levels assessed on days 5, 10, 14, 28, depending on study group | Up to Day 28 | |
Secondary | Rate of prescribing other anti-inflammatory therapy regimens (rescue therapy), depending on study group | Rate of prescribing other anti-inflammatory therapy regimens (rescue therapy), depending on study group | Up to day 28 |
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