Study of Efficacy of Different Treatment Regimens of Olokizumab

NCT05187793 | Unknown Phase 3 DMC

• 1 other identifier: CL04041094
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

COVID-19

Keywords

SARS-CoV-2; 2019-nCoV; Severe acute respiratory syndrome coronavirus 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

• CRP normalization rate

  Up to Day 28

• Ferritin normalization rate

  Up to Day 28

• D-dimer normalization rate

  Up to Day 28

• Mean CRP levels

  Up to Day 28

Other Outcomes (16)

• 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

• Clinical recovery rate at day 14

  Up to day 14

• Cumulative incidence of transfer to intensive care unit (ICU), transfer to mechanical ventilation, development of ARDS and / or death, at day 28

  Uo to day 28

Study Arms (2)

Olokizumab

EXPERIMENTAL

Subject randomized to receive intravenous infusion of 0,8 ml solution of Olokizumab, one (128 mg), or two (256 mg) doses, in addition to standard therapy in line with the current temporary guidelines "Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)" of the Ministry of Health of Russian Federation. Standard therapy includes: * Baricitinib, p.o., 4 mg once daily for 7 days * Favipiravir, p.o., * for patients weighing \<75 kg: 1600 mg twice daily on Day 1, then 600 mg twice daily from the 2nd to the 10th day; * for patients weighing ≥ 75 kg: 1800 mg twice daily on Day 1, then 800 mg twice daily from the 2nd to the 10th day; (Patients who have started etiotropic therapy with favipiravir or remdesivir prior to randomization will continue the initiated treatment.) * dexamethasone at doses of 4 - 20 mg / day or methylprednisolone at a dose of 1 mg / kg / intravenous injection every 12 hours.

Drug: Olokizumab; Drug: Standard therapy

Standard therapy

ACTIVE COMPARATOR

Standard therapy in line with the current temporary guidelines "Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)" of the Ministry of Health of Russian Federation including: * Baricitinib, p.o., 4 mg once daily for 7 days * Favipiravir, p.o., * for patients weighing \<75 kg: 1600 mg twice daily on Day 1, then 600 mg twice daily from the 2nd to the 10th day; * for patients weighing ≥ 75 kg: 1800 mg twice daily on Day 1, then 800 mg twice daily from the 2nd to the 10th day; (Patients who have started etiotropic therapy with favipiravir or remdesivir prior to randomization will continue the initiated treatment.) * dexamethasone at doses of 4 - 20 mg / day or methylprednisolone at a dose of 1 mg / kg / intravenous injection every 12 hours.

Drug: Standard therapy

Interventions

Olokizumab DRUG

Olokizumab, 128 mg, solution for subcutaneous administration 160 mg/mL

Olokizumab

Standard therapy DRUG

Standard treatment including: * Baricitinib, 4 mg, film coated tablets * Favipiravir, 200 mg, film coated tablets * Dexamethasone IV or IM OR Methylprednisolone IV

Olokizumab; Standard therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent for participation in this study.
• 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).
• 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.
• 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
• 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.
• Ability to follow protocol requirements and perform all clinical trial procedures.
• 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.

You may not qualify if:

• Hypersensitivity to olokizumab and / or other components of the study drug.
• Contraindications to favipiravir or glucocorticosteroids or Janus kinase inhibitors (baricitinib).
• 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.
• 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.

Sponsors & Collaborators

• R-Pharm: lead
• Federal Budget Institution of Science "Central Research Institute of Epidemiology" of the Rospotrebnadzor: collaborator
• Group of companies Medsi, JSС: collaborator

Study Sites (5)

State Budgetary Healthcare Institution "City Clinical Hospital named after F.I. Inozemtsev of Moscow Healthcare Department"

Moscow, 105187, Russia

Location

Federal State Budgetary Institution "Central Clinical Hospital with a Polyclinic" of Presidential Administration of the Russian Federation

Moscow, 121359, Russia

Location

State Budgetary Healthcare Institution "City Clinical Hospital № 52 of Moscow Healthcare Department"

Moscow, 123182, Russia

Location

State Budgetary Healthcare Institution "Infectious Diseases Hospital No. 1 of Moscow Healthcare Department"

Moscow, 125367, Russia

Location

State Budgetary healthcare Institution of the Voronezh region "Voronezh Regional Clinical Hospital No. 1"

Voronezh, 394066, Russia

Location

MeSH Terms

Conditions

COVID-19

Interventions

olokizumab; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2021
• First Posted: January 12, 2022
• Study Start: July 8, 2021
• Primary Completion: October 31, 2022
• Study Completion: April 1, 2023
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (5)