NCT04380519
Trial name or title	Study of the efficacy and safety of a single administration of olokizumab and RPH‐104 with standard therapy in patients with severe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection (COVID‐19)
Methods	RCT, placebo‐controlled, double‐blind study Date of study: May 2020 Location: Russian Federation Phase 2/3
Participants	Randomised: 372 participants Inclusion criteria Signed and dated patient's Informed consent for participation in this study, or record of a medical board decision justifying patient's participation in case of patient is unable to state his/her will. Having either of the following COVID‐associated respiratory syndromes: pneumonia with oxygenation parameters SpO2 ≤ 93% (on room air) or respiratory rate greater than 30/min; ARDS (PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315 if PaO2 is not available). COVID‐19 diagnosis based on: laboratory‐confirmed SARS‐CoV‐2 infection as determined by PCR method; or bilateral changes in the lungs typical for COVID‐19, based on chest computed tomography results. Exclusion criteria Hypersensitivity to the study drugs (RPH‐104 and/or OKZ), and/or its components Presence of any of the following laboratory abnormalities: absolute neutrophil counts < 0.5 x 10^9 L white blood cell count < 2 x 10^9 L platelet count < 50 x 10^9 L ALT and/or AST ≥ 3.0 x ULN Severe renal failure: creatinine clearance < 30 mL/min Septic shock (to maintain mean arterial pressure ≥ 65 mm Hg and lactate ≥ 2 mmol/L in the absence of hypovolaemia, vasopressors are necessary) Progression of disease up to the death in the following 24 hours regardless of treatment, as per Investigator's opinion History of perforation of gastrointestinal tract, history of diverticulitis Plasma infusion from convalescent COVID‐19 donors within 4 weeks prior to patient inclusion and/or planned infusion during the study Recent (less then 5 half‐lives) administration of tocilizumab or sarilumab; Recent (less then 5 half‐lives) or planned during the current study period use of the following drugs: immunosuppressive biologics over than OKZ or RPH‐104, including but not limited, Interleukin‐1 (IL‐1) inhibitors (rilonacept, anakinra, canakinumab), IL‐6 inhibitors (except tocilizumab and sarilumab), IL‐17A inhibitors (secukinumab), tumour necrosis factor α (TNFα) inhibitors (adalimumab, infliximab, etanercept), anti‐B‐cell therapy and others other immunosuppressors except methotrexate dosed up to 25 mg per week, including but not limited: high‐dose glucocorticoids (> 1 mg/kg of prednisolone equivalent), oral and parental; JAK inhibitors, cyclophosphamide, and others Concurrent participation in another clinical trial Pregnancy or lactation History of active tuberculosis, active tuberculosis suspected by Investigator
Interventions	Intervention RPH‐104 (SC, 80 mg, single injection) Olokizumab (SC, 64 mg, single injection) Control interventions Placebo
Outcomes	Primary outcome Secondary outcomes Changes of patients' clinical status on a 6 points ordinal scale (day 2 until day 15, day 29) Mortality (day 1 until day 29) Time to clinical improvement of clinical status (day 1 until day 29)
Starting date	Study start date: 23 April 2020 Study completion date: 24 July 2020
Contact information	R‐Pharm, Mikhail Samsonov
Notes	Completed