Study of the Outcomes of Olokizumab Therapy in Hospitalized Patients With SARS-CoV-2 (COVID-19) Infection (ROCOVI)

• ClinicalTrials.gov Identifier: NCT05196477
• Recruitment Status: Completed
• First Posted: January 19, 2022
• Last Update Posted: January 20, 2023
• Sponsor: R-Pharm
• Collaborators: Almedis LLC; Data Management 365; ScienceFiles LLC
• Information provided by (Responsible Party): R-Pharm

Tracking Information

• First Submitted Date: January 18, 2022
• First Posted Date: January 19, 2022
• Last Update Posted Date: January 20, 2023
• Actual Study Start Date: July 14, 2021
• Actual Primary Completion Date: August 29, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2022)

The percentage of patients who died during hospital admission due to any reason [ Time Frame: up to 21 days ]

The percentage of patients who died during hospital admission due to any reason in each therapy group

Original Primary Outcome Measures (submitted: January 18, 2022)

The proportion of patients who required mechanical ventilation or transfer to intensive care unit, or who died after olokizumab therapy during hospital admission due to COVID-19. [ Time Frame: up to day 21 ]

The proportion of patients who required mechanical ventilation or transfer to intensive care unit, or who died after olokizumab therapy during hospital admission due to COVID-19.

Current Secondary Outcome Measures (submitted: June 27, 2022)

• The percentage of patients who required mechanical ventilation or transfer to intensive care unit (ICU), or who died during hospital admission due to COVID-19 [ Time Frame: up to day 21 ]
  The percentage of patients who required mechanical ventilation or transfer to ICU, or who died after olokizumab therapy during hospital admission due to COVID-19.
• The percentage of patients who required transfer to ICU [ Time Frame: up to day 21 ]
  The percentage of patients who required transfer to ICU in each therapy group
• The percentage of patients who required transfer to a new type of oxygen support and to an invasive mechanical ventilation (MV) [ Time Frame: up to day 21 ]
  The transfer to a new type of oxygen support means the transfer to a more severe type of oxygen support (the appointment of low-current oxygen to patients who were initially without oxygen support; transfer from low-flow oxygen therapy to high-flow, non-invasive or invasive ventilation; from high-flow oxygen therapy to non-invasive or invasive ventilation; from non-invasive to invasive ventilation).
• Overall hospitalisation period [ Time Frame: from admission to discharge from hospital, up to 21 days ]
  Overall hospitalisation period duration in each therapy group (in days)

Original Secondary Outcome Measures (submitted: January 18, 2022)

• Overall hospitalisation period [ Time Frame: from admission to discharge from hospital, up to 21 days ]
  Overall hospitalisation period in days
• Duration of intensive care unit (ICU) stay [ Time Frame: from admission to discharge from ICU, up to 21 days ]
  Duration of ICU stay in days
• Percentage of intensive care unit (ICU) stay duration [ Time Frame: up to 21 days ]
  Percentage of ICU stay duration to overall hospitalisation period
• Proportion of patients on mechanical ventilation (MV) (with intubation or tracheostoma) [ Time Frame: up to 21 days ]
  Proportion of patients on MV (with intubation or tracheostoma)
• Proportion of patients receiving other interleukin (IL) inhibitors after olokizumab administration [ Time Frame: up to 21 days ]
  Proportion of patients receiving other IL inhibitors after olokizumab administration
• Duration of MV [ Time Frame: up to 21 days ]
  Duration of MV in days
• Proportion of patients with 2-fold C-reactive protein (CRP) level reduction [ Time Frame: day 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group) ]
  Proportion of patients with 2-fold CRP level reduction relative to peak value assessed on day 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group.
• Changes from peak values of the CRP levels [ Time Frame: 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group, day of discharge or in-hospital day 21 ]
  Changes from peak values of the CRP levels assessed on day 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group, on day of discharge or in-hospital day 21.
• Changes in percentage from peak values of the CRP levels [ Time Frame: 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group, day of discharge or in-hospital day 21 ]
  Changes in percentage from peak values of the CRP levels assessed on day 7 after olokizumab administration or after appearance of indications for preemptive anti-inflammatory therapy in the control group, on day of discharge or in-hospital day 21.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Outcomes of Olokizumab Therapy in Hospitalized Patients With SARS-CoV-2 (COVID-19) Infection
• Official Title: Multicentre Non-interventional Retrospective Cohort Study of the Outcomes of Olokizumab Therapy in Hospitalized Patients With SARS-CoV-2 (COVID-19) Infection
• Brief Summary: The study purpose was to assess the outcomes of therapy with olokizumab within complex therapy of Coronavirus disease 2019 (COVID-19) in hospitalised patients in real clinical practice setting. The study investigated patients' characteristics, disease progression, and efficacy and safety of olokizumab therapy.

Detailed Description

This was a multicentre retrospective cohort study of patients admitted to hospitals in various Russian Federation cities with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid (RNA) laboratory test for the treatment of severe acute respiratory syndrome. The study used information from primary medical documentation of COVID-19 patients who had underwent diagnostic and therapeutic procedures in accordance with the hospital clinical practice. Clinical and laboratory data was collected and analysed to assess olokizumab safety, investigate other treatments, course and outcomes of the disease.

No additional tests or medical procedures were made as part of this study. If any data collected under the protocol was not available or not collected, they deemed lacking.

Based on the results of preliminary assessment of the number of records from the patients meeting inclusion / exclusion criteria in the clinical sites planning to participate in the project it was planned to include no more than 3000 patients in the study, of which about 1500 would be in the main group (received olokizumab therapy), and 1500 would be in the comparison group. It was planned to conduct an analysis in the general population (including taking into account its balancing using statistical methods, in case of significant differences in the initial characteristics of patients in groups), as well as in a subpopulation selected from pairs formed taking into account the comparability of patients by individual characteristics. In total, it was planned to form at least 200 pairs (or more, if the included population is highly comparable). Participation of several clinics in Russian Federation cities (not more than 10 cites) was expected to assure sufficient population for the study.

Data collection period for each hospitalised patient was equivalent to in-hospital period for the treatment of SARS-CoV-2 infection. Data collection by patients was made during hospital stay, including the day of discharge (treatment outcome or lethal outcome). The primary study variables were defined during 21-day observation period.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: The study enrolls males and females aged ≥ 18 years with infection caused by SARS-CoV-2 who received in-hospital therapy. The study population includes all the patients admitted to hospital since June 2020, meeting inclusion / exclusion criteria with their data collected and analysed.
• Condition: COVID-19

Intervention

• Drug: Olokizumab
  The details of taking olokizumab, including its route of administration, dose and frequency of taking the drug as part of routine clinical practice, will be registered in the electronic case report forms (eCRFs).
• Drug: Standard therapy
  Standard treatment (excluding administration of olokizumab, other interleukin (IL) (interleukin-1 and interleukin-17) inhibitors and Janus-kinase inhibitors.

Study Groups/Cohorts

• Olokizumab treatment group
  Subjects with the infection caused by SARS-CoV-2 who received olokizumab injection in addition to the standard therapy.
  Interventions:

  • Drug: Olokizumab
  • Drug: Standard therapy
• Standard treatment group
  Subjects with the infection caused by SARS-CoV-2 who received the standard therapy without monoclonal antibodies (mAbs).
  Intervention: Drug: Standard therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 18, 2023): 3087
• Original Actual Enrollment (submitted: January 18, 2022): 1911
• Actual Study Completion Date: August 29, 2022
• Actual Primary Completion Date: August 29, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of SARS-CoV-2 (using virus ribonucleic acid polymerase chain reaction (RNA PCR) test).
• Hospital admission for COVID-19 therapy.
• Infiltrative lung changes based on imaging findings (chest X-ray, chest computed tomography (CT)).

• Indications for Preemptive anti-inflammatory therapy (PAT), including two or more signs below:

  • reduced oxygen saturation of the blood SpO2 ≤ 97 %
  • C-reactive protein (CRP) > 15 mg/L
  • body temperature > 37.5 °C for at least 3 days
  • white blood cell count < 4.0 x 10^9/L
  • absolute lymphocyte count < 2.0 x 10^9/L.
• Olokizumab therapy - for the test group.
• Source medical documents contain the information required for the study (lacking or incomplete data on some serum chemistry values are allowed: D-dimer, ferritin, IL-6, procalcitonin).

Exclusion Criteria:

• Inadequate information on patient's characteristics and therapy.
• Lack of documented confirmation of SARS-CoV-2 infection.
• Initiation of mechanical ventilation (MV) from the first day of admission in the control group or before olokizumab administration in the test group.
• Administration of systemic corticosteroids, IL-6, other immunosuppressants or immunoglobulins before hospital admission.
• Lack of indications to PAT
• Administration of olokizumab, other interleukin (IL) (interleukin-1 and interleukin-17) inhibitors and Janus-kinase inhibitors - for comparator group.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT05196477
• Other Study ID Numbers: CL04041090
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: R-Pharm
• Original Responsible Party: Same as current
• Current Study Sponsor: R-Pharm
• Original Study Sponsor: Same as current

Collaborators

• Almedis LLC
• Data Management 365
• ScienceFiles LLC

Investigators

• Study Director: Mikhail Samsonov; R-Pharm

• PRS Account: R-Pharm
• Verification Date: January 2023