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)

NCT04380519 | Completed Phase 2 Results DMC

• 1 other identifier: CL04041078
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 16

Brief Summary

The primary objective of the study was to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study.

Conditions

COVID-19

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Proportion of Responders in Each Treatment Group

  Proportion of patients, responded to the study therapy, in each of the treatment groups. A responder is a patient who has not received tocilizumab or sarilumab and who has a clinical status improvement of ≥1 point on the 6-point COVID-19 scale (where 1 is the most favorable outcome and 6 is the most undesirable outcome) 15 days after the administration of the study drug: 1. Not hospitalized, no activity limitations. 2. Not hospitalized, limited activity. 3. Hospitalized, not requiring supplemental oxygen. 4. Hospitalized, supplemental oxygen with independent breathing. 5. Hospitalized; mechanical ventilation (invasive/non-invasive) or Extracorporeal membrane oxygenation (ECMO). 6. Death.

  Day 15

Secondary Outcomes (4)

• Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale

  from Day 2 until Day 15, Day 29

• The Proportion of Patients With an Improvement in Clinical Status by 2 or More Points on the 6-point Ordinal Scale During the Study With no Use of Tocilizumab or Sarilumab

  Day 29

• The Proportion of Patients Who Received Tocilizumab or Sarilumab for COVID-19 During the Study

  from Day 2 until the Day 29

• Mortality Rate During the Study

  from Day 1 until Day 29

Study Arms (3)

RPH -104 80 mg

EXPERIMENTAL

Subject randomized to receive subcutaneous single injection of 2 ml solution of RPH-104 on Day 1, in addition to standard therapy

Drug: RPH-104 80 mg

Olokizumab 64 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Subject randomized to receive subcutaneous single injection of 2 ml solution of Placebo on Day 1, in addition to standard therapy

Drug: Placebo

Interventions

RPH-104 80 mg DRUG

solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial

RPH -104 80 mg

Olokizumab 64 mg DRUG

solution for subcutaneous administration 160 mg/mL, in the 2-mL glass vial (target volume 0,4 ml)

Olokizumab 64 mg

Placebo DRUG

Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The presence of a voluntarily signed and dated Patient Informed Consent Form for participation in this study, or a record of an Medical Consilium 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 saturation SpO2 ≤93% (on room air) or respiratory rate greater than 30/min;
• Acute respiratory distress syndrome (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 Polymerase Chain Reaction method (PCR).
• Bilateral changes in the lungs typical for COVID-19, based on chest computed tomography results.

You may not qualify if:

• A history of hypersensitivity to the study drugs (RPH-104 and/or OKZ), and/or their components.
• The 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
• Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) ≥ 3.0 x Upper Limit of Normal (ULN)
• Severe renal failure: creatinine clearance \< 30 mL/min
• Septic shock (vasopressors are required to maintain mean arterial pressure ≥ 65 mm Hg and lactate ≥ 2 mmol/L in the absence of hypovolemia)
• The disease progresses to death over the next 24 hours, regardless of treatment, according to Investigator.
• Perforation of the gastrointestinal tract, a history of diverticulitis.
• Administration of plasma from COVID-19 convalescent donors within 4 weeks before study enrollment and/or planned administration 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:
• biologics (except RPH-104 or OKZ) with immunosuppressive effect, including, but not limited to: Interleukin-1 (IL-1) inhibitors (anakinra, rilonacept, canakinumab), IL- 6 inhibitors (except tocilizumab and sarilumab), IL-17A inhibitors (secukinumab), tumor necrosis factor α (TNFα) inhibitors (infliximab, adalimumab, etanercept, etc.), antiB-cell drugs, etc.
• other immunosuppressive drugs (with the exception of methotrexate in a dose of up to 25 mg/week), including, but not limited to:

Sponsors & Collaborators

• R-Pharm International, LLC: lead
• Data Management 365: collaborator
• K-Research, LLC: collaborator

Study Sites (16)

Private healthcare institution "Clinical Hospital" Russian Railways-Medicine named after N. A. Semashko"

Moscow, 109386, Russia

Location

State Budget Healthcare Institution "City Clinical Hospital № 15 named after O.M. Filatov" of Moscow City Healthcare Department

Moscow, 111539, Russia

Location

Federal State Budgetary Institution "Federal Center for Cerebrovascular Pathology and Stroke" of the Ministry of Health of the Russian Federation

Moscow, 117997, Russia

Location

Federal State Autonomous Education Insitution of High Education the First Moscow State Medical University named after I.M. Sechenov of Ministry of Healthcare of Russian Federation (Sechenov University)

Moscow, 119991, Russia

Location

Federal State Autonomous Education Institution of High Education the First Moscow State Medical University named after I.M. Sechenov of Ministry of Healthcare of the Russian Federation (Sechenov University)

Moscow, 119991, Russia

Location

Federal State Budgetary Institution "Central Clinical Hospital with Polyclinic" of Administrative Directorate of the President of the Russian Federation

Moscow, 121359, Russia

Location

Federal State Budget Institution "National Medicine Research Center on Cardiology" By Ministry of Healthcare of Russian Federation

Moscow, 121552, Russia

Location

State Budget Institution of Healthcare "City Clinical Hospital #52", Moscow City Healthcare Department

Moscow, 123182, Russia

Location

State budgetary healthcare institution City Clinical Hospital named after S.I. Spasokukotsky Department of Health of the city of Moscow City Clinical Hospital No. 50

Moscow, 127206, Russia

Location

Moscow State Budget Institution of Healthcare "Scientific Research Institute of Emergency Medicine named after N.V. Sklifosovsky of Moscow Department of Healthcare"

Moscow, 129090, Russia

Location

АО "State Company "Medsi" based on Clinical Hospital №1"

Moscow, 143442, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "Volga Research Medical University" of the Ministry of Health of the Russian Federation

Nizhny Novgorod, 603950, Russia

Location

Federal Budgetary State Healthcare Institution "National Medical Research Center named after B.A. Almazov"

Saint Petersburg, 197341, Russia

Location

Saint-Petersburg State Budget Institution of Healthcare "City Hospital №40"

Saint Petersburg, 197706, Russia

Location

Budgetary Health Institution Voronezh Regional Clinical Hospital №1

Voronezh, 394066, Russia

Location

State Budget Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Hospital of War Veterans"

Yaroslavl, 150047, Russia

Location

MeSH Terms

Conditions

COVID-19; Respiration Disorders; Lung Diseases; Coronavirus Infections

Interventions

olokizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Sergey Grishin, Head of Scientific Affairs Department
• Organization: R-Pharm

sa.grishin@rpharm.ru

0074959567937

Study Officials

• Mikhail Samsonov

  Chief Medical Officer, R-Pharm

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 8, 2020
• Study Start: April 23, 2020
• Primary Completion: July 10, 2020
• Study Completion: July 24, 2020
• Last Updated: January 24, 2022
• Results First Posted: January 24, 2022

Record last verified: 2022-01

Locations

RU (16)