Back to resultsStudy of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19).
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Olokizumab 64 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, 2019-nCoV, 2019 novel coronavirus, Respiratory disease, lung disease, COVID-19, coronavirus
Eligibility Criteria
Inclusion Criteria:
- COVID-19 diagnosis (confirmation of the presence of SARS-CoV-2 virus by rt-PCR) OR sample collection for SARS-CoV-2 virus rt-PCR if the results of SARS-CoV-2 virus rt-PCR are not available yet.
- Dated informed consent for participation in this study signed by the patient, or by the legally acceptable representative or when prior consent of the patient is not possible, and the subject's legally acceptable representative is not available, documented approval / favorable opinion by the IRB/IEC.
- SpO2 ≤93% (room air) or respiratory rate greater than 30/min (room air) or oxygenation index PaO2/FiO2 ≤300 mmHg (or SpO2/FiO2 ≤315 in the case PaO2/FiO2 assessment is not available (supplementary oxygen)
- Computed tomography findings: features consistent with bilateral COVID-19 viral pneumonia and no alternative explanation for these findings.
Exclusion Criteria:
- Presence of any of the following laboratory abnormalities:
absolute neutrophil counts <0,5 х 10^9/L white blood cell count < 2 х 10^9/L, platelet count < 50 х 10^9/L, Alanine aminotransferase (АLT) and/or Aspartate aminotransferase (AST) ≥3,0 х Upper Limit of Normal (ULN)
- Kidney injury with creatinine clearance <30 mL/min.
- Hypersensitivity to OKZ, and/or its components.
- Septic shock (need for vasopressors to maintain mean arterial pressure ≥ 65 mm Hg and lactate ≥2 mmol / L in the absence of hypovolemia).
- Estimated survival of less than 24 hours regardless of treatment.
- History of perforation of the gastrointestinal tract, history of diverticulitis.
- Recent (less than 5 half-lives), current or planned during the current study period use of immunosuppressive drugs:
- biologics (except OKZ) with immunosuppressive effect, including, but not limited to: Interleukin-1 (IL-1) inhibitors (anakinra, rilonacept, canakinumab), IL-6 inhibitors (tocilizumab, sarilumab, siltuximab, etc.), IL-17A inhibitors (seсukinumab, etc.), Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors (infliximab, adalimumab, etanercept, etc.), anti-B-cells therapy, etc.;.
other immunosuppressive drugs (excluding methotrexate in dose up to 25 mg/week), including but not limited to:
- Glucocorticoids in high doses (> 1 mg / kg equivalent of methylprednisolone) orally and parenterally;
- JAK inhibitors; etc.
- Concurrent participation in another clinical trial during 30 days before screening.
- Pregnancy or lactation.
- A history of active tuberculosis, or active tuberculosis suspected by the Investigator.
- Administration of plasma from COVID-19 reconvalescent donors for 4 weeks prior to the patient's inclusion in the study and/or planned administration during the study
- Patients who deteriorated into Category 4 of the 5-point clinical status scale within more than the last 24 hours.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Olokizumab 64 mg
Placebo
Arm Description
Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy
Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Placebo on Day 1, in addition to standard therapy
Outcomes
Primary Outcome Measures
Percentage of subjects achieving a change in their clinical status defined as improvement for at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category
Difference between OKZ and placebo groups in the percentage of subjects with an improvement of at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category. The points of the scale are: 1. Not hospitalized; 2.Hospitalized, not requiring supplemental oxygen; 3.Hospitalized, supplemental oxygen, spontaneous breathing;4. Hospitalized, mechanical ventilation (invasive/non-invasive) or extracorporeal membrane oxygenation (ECMO); 5. Death
Secondary Outcome Measures
Subjects' clinical status distribution based on 5-point clinical status scale during the study
Subjects' clinical status distribution based on 5-point clinical status scale during the study
28-day case fatality rates
28-day case fatality rates
Full Information
NCT ID
NCT04452474
First Posted
June 25, 2020
Last Updated
October 29, 2021
Sponsor
R-Pharm
Collaborators
Cromos Pharma LLC, Covance
1. Study Identification
Unique Protocol Identification Number
NCT04452474
Brief Title
Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19).
Official Title
A Multicenter, Randomized, Double-blind, Adaptive, Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe SARS-CoV-2 Infection (COVID-19)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor's decision
Study Start Date
June 30, 2020 (Anticipated)
Primary Completion Date
November 16, 2020 (Anticipated)
Study Completion Date
January 29, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
R-Pharm
Collaborators
Cromos Pharma LLC, Covance
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to evaluate the efficacy of a single dose of OKZ (64 mg) vs placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 29.
Detailed Description
Pilot phase: the first 100 patients will be randomized in two groups to receive OKZ or placebo (50 patients per group). Early futility analysis will be performed based on the results obtained in the pilot period after 100th patient completed Visit 29. Enrollment will be paused after randomization of 100th patient, then interim analysis will be performed when all 100 patients complete Visit Day 29 or discontinue the study.Based on results of the pilot phase analysis the study could be stopped.
Pivotal phase: inclusion of patients until targeted sample size is reached and performing final safety and efficacy analysis.
Maximum expected study duration for each patient is 62 days, including 2 days of screening, 1 day of study drug administration, and 59 days of follow-up.
The study will include following periods:
Screening period lasting up to 48 hours prior to Day 1. After signing the informed consent by the patient or the legally acceptable representative or when prior consent of the patient is not possible, and the subject's legally acceptable representative is not available, after obtaining documented approval/favorable opinion for individual cases by the Institutional Review Board / Independent Ethic Committee (IRB/IEC), investigator will assess the subject's eligibility for the study.
Treatment period lasting from the beginning of Day 1 visit to 23:59 of the Day 1.
Eligible patients will be randomized to one of two treatment groups to receive a single subcutaneous injection - OKZ 64 mg or placebo in addition to standard COVID-19 therapy according to institutional guidelines;
Follow-up period lasting from 00:00 of the Day 2 to 23:59 of the Day 60. If the patient is discharged earlier than Day 15, at Days 15 and 29 5-point clinical status scale will be assessed at the study site visit or by phone interview. If the patient is discharged after Day 15, but earlier than Day 29, at Day 29 5-point clinical status scale will be assessed at the study site visit or by phone interview. The end of study is Day 60, when 5-point clinical status scale will be assessed by phone interview.
Up to 376 randomized patients (full sample size) will be included in the study according to preliminary estimation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, 2019-nCoV, 2019 novel coronavirus, Respiratory disease, lung disease, COVID-19, coronavirus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olokizumab 64 mg
Arm Type
Experimental
Arm Description
Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Placebo on Day 1, in addition to standard therapy
Intervention Type
Drug
Intervention Name(s)
Olokizumab 64 mg
Intervention Description
solution for subcutaneous administration 160 mg/mL
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package
Primary Outcome Measure Information:
Title
Percentage of subjects achieving a change in their clinical status defined as improvement for at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category
Description
Difference between OKZ and placebo groups in the percentage of subjects with an improvement of at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category. The points of the scale are: 1. Not hospitalized; 2.Hospitalized, not requiring supplemental oxygen; 3.Hospitalized, supplemental oxygen, spontaneous breathing;4. Hospitalized, mechanical ventilation (invasive/non-invasive) or extracorporeal membrane oxygenation (ECMO); 5. Death
Time Frame
at Day 29
Secondary Outcome Measure Information:
Title
Subjects' clinical status distribution based on 5-point clinical status scale during the study
Description
Subjects' clinical status distribution based on 5-point clinical status scale during the study
Time Frame
from Day 2 tо Day 15, Day 29, Day 60
Title
28-day case fatality rates
Description
28-day case fatality rates
Time Frame
from Day 1 to Day 29
Other Pre-specified Outcome Measures:
Title
Case fatality rates during the intensive care unit (ICU) stay, at Days 7, 15, and 60
Description
Case fatality rates during the intensive care unit (ICU) stay at Days 7, 15, and 60
Time Frame
from Day 1 to Day 60
Title
Duration of oxygen support
Description
Duration of oxygen support (if applicable)
Time Frame
From Day 1 to Day 60
Title
The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached
Description
The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached
Time Frame
from Day 2 to Day 60
Title
Changes of oxygenation index PaO2/FiO2 from baseline
Description
Changes of oxygenation index PaO2/FiO2 from baseline (if applicable)
Time Frame
from Day 2 to Day 60
Title
Duration of oxygen support (if applicable)
Description
Duration of oxygen support (if applicable), in days
Time Frame
from Day 1 to Day 60
Title
Duration of mechanical ventilation and/or ECMO (if applicable)
Description
Duration of mechanical ventilation and/or ECMO (if applicable), in days
Time Frame
from Day 1 to Day 60
Title
Duration of ICU stay (if applicable)
Description
Duration of ICU stay (if applicable)
Time Frame
from Day 1 to Day 60
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte count
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte counts
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides
Description
Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides
Time Frame
from Day 2 and until the end of hospitalization, Day 29 as a maximum
Title
The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached
Description
The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached
Time Frame
from Day 1 and until the end of hospitalization, Day 29 as a maximum
Title
The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached
Description
The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached
Time Frame
from Day 1 and until the end of hospitalization, Day 29 as a maximum
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
COVID-19 diagnosis (confirmation of the presence of SARS-CoV-2 virus by rt-PCR) OR sample collection for SARS-CoV-2 virus rt-PCR if the results of SARS-CoV-2 virus rt-PCR are not available yet.
Dated informed consent for participation in this study signed by the patient, or by the legally acceptable representative or when prior consent of the patient is not possible, and the subject's legally acceptable representative is not available, documented approval / favorable opinion by the IRB/IEC.
SpO2 ≤93% (room air) or respiratory rate greater than 30/min (room air) or oxygenation index PaO2/FiO2 ≤300 mmHg (or SpO2/FiO2 ≤315 in the case PaO2/FiO2 assessment is not available (supplementary oxygen)
Computed tomography findings: features consistent with bilateral COVID-19 viral pneumonia and no alternative explanation for these findings.
Exclusion Criteria:
Presence of any of the following laboratory abnormalities:
absolute neutrophil counts <0,5 х 10^9/L white blood cell count < 2 х 10^9/L, platelet count < 50 х 10^9/L, Alanine aminotransferase (АLT) and/or Aspartate aminotransferase (AST) ≥3,0 х Upper Limit of Normal (ULN)
Kidney injury with creatinine clearance <30 mL/min.
Hypersensitivity to OKZ, and/or its components.
Septic shock (need for vasopressors to maintain mean arterial pressure ≥ 65 mm Hg and lactate ≥2 mmol / L in the absence of hypovolemia).
Estimated survival of less than 24 hours regardless of treatment.
History of perforation of the gastrointestinal tract, history of diverticulitis.
Recent (less than 5 half-lives), current or planned during the current study period use of immunosuppressive drugs:
biologics (except OKZ) with immunosuppressive effect, including, but not limited to: Interleukin-1 (IL-1) inhibitors (anakinra, rilonacept, canakinumab), IL-6 inhibitors (tocilizumab, sarilumab, siltuximab, etc.), IL-17A inhibitors (seсukinumab, etc.), Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors (infliximab, adalimumab, etanercept, etc.), anti-B-cells therapy, etc.;.
other immunosuppressive drugs (excluding methotrexate in dose up to 25 mg/week), including but not limited to:
Glucocorticoids in high doses (> 1 mg / kg equivalent of methylprednisolone) orally and parenterally;
JAK inhibitors; etc.
Concurrent participation in another clinical trial during 30 days before screening.
Pregnancy or lactation.
A history of active tuberculosis, or active tuberculosis suspected by the Investigator.
Administration of plasma from COVID-19 reconvalescent donors for 4 weeks prior to the patient's inclusion in the study and/or planned administration during the study
Patients who deteriorated into Category 4 of the 5-point clinical status scale within more than the last 24 hours.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikhail Samsonov
Organizational Affiliation
Chief Medical Officer, R-Pharm
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19).
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