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).

• ClinicalTrials.gov Identifier: NCT04452474
• Recruitment Status: Not yet recruiting
• First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Sponsor: R-Pharm
• Collaborators: Cromos Pharma, LLC; Covance
• Information provided by (Responsible Party): R-Pharm

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Olokizumab 64 mg; Drug: Placebo	Phase 2; Phase 3

Detailed Description:

1. 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.
2. 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:

1. 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.

2. 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;

3. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 376 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: June 30, 2020
• Estimated Primary Completion Date: November 16, 2020
• Estimated Study Completion Date: January 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Olokizumab 64 mg; Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy	Drug: Olokizumab 64 mg; solution for subcutaneous administration 160 mg/mL
Placebo Comparator: Placebo; Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Placebo on Day 1, in addition to standard therapy	Drug: Placebo; Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: at Day 29 ]
   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 :

1. 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 ]
   Subjects' clinical status distribution based on 5-point clinical status scale during the study
2. 28-day case fatality rates [ Time Frame: from Day 1 to Day 29 ]
   28-day case fatality rates

Other Outcome Measures:

1. Case fatality rates during the intensive care unit (ICU) stay, at Days 7, 15, and 60 [ Time Frame: from Day 1 to Day 60 ]
   Case fatality rates during the intensive care unit (ICU) stay at Days 7, 15, and 60
2. Duration of oxygen support [ Time Frame: From Day 1 to Day 60 ]
   Duration of oxygen support (if applicable)
3. The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached [ Time Frame: from Day 2 to Day 60 ]
   The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached
4. Changes of oxygenation index PaO2/FiO2 from baseline [ Time Frame: from Day 2 to Day 60 ]
   Changes of oxygenation index PaO2/FiO2 from baseline (if applicable)
5. Duration of oxygen support (if applicable) [ Time Frame: from Day 1 to Day 60 ]
   Duration of oxygen support (if applicable), in days
6. Duration of mechanical ventilation and/or ECMO (if applicable) [ Time Frame: from Day 1 to Day 60 ]
   Duration of mechanical ventilation and/or ECMO (if applicable), in days
7. Duration of ICU stay (if applicable) [ Time Frame: from Day 1 to Day 60 ]
   Duration of ICU stay (if applicable)
8. 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 ]
   Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count
9. Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte count [ Time Frame: from Day 2 and until the end of hospitalization, Day 29 as a maximum ]
   Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte counts
10. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count
11. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)
12. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin
13. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer
14. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets
15. 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 ]
    Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides
16. 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 ]
    The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached
17. 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 ]
    The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

  1. Glucocorticoids in high doses (> 1 mg / kg equivalent of methylprednisolone) orally and parenterally;
  2. 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.

Contacts and Locations

Locations

United States, District of Columbia

George Washington University Medical Center

Washington, District of Columbia, United States, 20037

Contact: David Parenti 301-873-2862 dparenti@mfa.gwu.edu

United States, Georgia

Center For Haptitis C/ Atlanta Medical Center

Atlanta, Georgia, United States, 30312

United States, Illinois

PMG Research of DuPage Medical Group

Downers Grove, Illinois, United States, 60515

Contact: Karan Fachet 630-942-7956 karan.fachet@pmg-research.com

Contact: Viveka Boddapalli 630-942-7956

United States, Indiana

Northwest Indiana Center for Clinical Research

Portage, Indiana, United States, 46383-5539

Contact: Robert Buynak 219-241-9393 rbuynak@att.net

United States, Massachusetts

Baystate Infectious Diseases Clinical Research

Springfield, Massachusetts, United States, 01107

Contact: Daniel Skiest 413-794-7394 daniel.skiest@bhs.org

Contact: Judith Pride 4137947671 judith.pride@baystatehealth.org

United States, North Carolina

PMG Research, Inc.

Winston-Salem, North Carolina, United States, 27104

Contact: Jennifer Killion 515-956-4159 jkillon@mcfarlandclinic.com

Sponsors and Collaborators

R-Pharm

Cromos Pharma, LLC

Covance

Investigators

• Study Director: Mikhail Samsonov; Chief Medical Officer, R-Pharm

More Information

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT04452474
• Other Study ID Numbers: CL04041080
• First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Last Verified: June 2020

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

Keywords provided by R-Pharm:

SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; 2019 novel coronavirus; Respiratory disease; lung disease; COVID-19; coronavirus

Additional relevant MeSH terms:

Coronavirus Infections; Severe Acute Respiratory Syndrome; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases