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.
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.
Drug: Olokizumab 64 mg
solution for subcutaneous administration 160 mg/mL
Drug: Placebo
Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package
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.
George Washington University Medical Center
Washington, District of Columbia, 20037
Investigator: David Parenti
Contact: 301-873-2862
Center For Haptitis C/ Atlanta Medical Center
Atlanta, Georgia, 30312
PMG Research of DuPage Medical Group
Downers Grove, Illinois, 60515
Investigator: Karan Fachet
Contact: 630-942-7956
Investigator: Viveka Boddapalli
Contact: 630-942-7956
Northwest Indiana Center for Clinical Research
Portage, Indiana, 46383-5539
Investigator: Robert Buynak
Contact: 219-241-9393
Baystate Infectious Diseases Clinical Research
Springfield, Massachusetts, 01107
Investigator: Daniel Skiest
Contact: 413-794-7394
Investigator: Judith Pride
Contact: 4137947671
PMG Research, Inc.
Winston-Salem, North Carolina, 27104
Investigator: Jennifer Killion
Contact: 515-956-4159
Mikhail Samsonov, Study Director
Chief Medical Officer, R-Pharm