A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia

NCT04409262 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: WA425112020-002275-34
• Study Type: interventional
• Target: 649
• Locations: 4 countries
• Sites: 54

Brief Summary

This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (1)

• Time to Hospital Discharge or "Ready for Discharge" up to Day 28

  Defined as days from randomization to hospital discharge or "Ready for Discharge" not followed by ordinal scale category \>1, hospital readmission or death. Hospital discharge or "Ready for Discharge" is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

  Up to Day 28

Secondary Outcomes (16)

• Time to Mechanical Ventilation or Death up to Day 28

  Up to Day 28

• Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14

  Day 14

• Time to Death up to Day 28

  Up to Day 28

• Time to Death up to Day 60

  Up to Day 60

• Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28

  Up to Day 28

Other Outcomes (2)

• Percentage of Participants With Adverse Events (AEs) Tabulated by Severity

  Up to Day 60

• Proportion of Participants With Any Post-Treatment Infection

  Up to Day 60

Study Arms (2)

Remdesivir + Tocilizumab (RDV+TCZ)

EXPERIMENTAL

Participants assigned to the RDV+TCZ arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ on Day 1.

Drug: Remdesivir; Drug: Tocilizumab

Remdesivir + Placebo (RDV+Placebo)

ACTIVE COMPARATOR

Participants assigned to the RDV+ placebo arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ-placebo on Day 1.

Drug: Remdesivir; Drug: Placebo

Interventions

Remdesivir DRUG

Participants will receive intravenous (IV) RDV

Remdesivir + Placebo (RDV+Placebo); Remdesivir + Tocilizumab (RDV+TCZ)

Tocilizumab DRUG

Participants will receive IV TCZ

Remdesivir + Tocilizumab (RDV+TCZ)

Placebo DRUG

Participants will receive IV placebo matched to TCZ

Remdesivir + Placebo (RDV+Placebo)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized with COVID-19 pneumonia confirmed per a positive polymerase chain reaction (PCR) of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
• Requiring more than 6 L/min supplemental oxygen to maintain SpO2 \> 93%
• Agrees to not participate in another clinical trial for the treatment of COVID-19 while participating in this study

You may not qualify if:

• Known severe allergic reactions to tocilizumab or other monoclonal antibodies
• Known hypersensitivity to remdesivir, the metabolites, or formulation excipients
• Active tuberculosis (TB) infection
• Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Treatment with immunosuppressive or immunomodulatory therapy (including tocilizumab) within the past 3 months
• Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 within 24 hours prior to study drug dosing. In addition, participants with prior or current treatment with \> 2 doses of remdesivir for COVID-19 are excluded
• Participating in other drug clinical trials
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min (including patients receiving hemodialysis or hemofiltration)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN) detected within 24 hours of screening (according to local laboratory reference ranges)
• Absolute neutrophil count (ANC) \< 1000/uL at screening
• Platelet count \< 50,000/uL at screening
• Body weight \< 40 kg
• Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Gilead Sciences: collaborator

Study Sites (54)

Valleywise Health Medical Center

Phoenix, Arizona, 85008, United States

Location

eStudySite - Chula Vista - PPDS

Chula Vista, California, 91911, United States

Location

Hoag Hospital Irvine

Irvine, California, 92612, United States

Location

Providence St Johns Health Center

Santa Monica, California, 90404, United States

Location

Yale University School of Medicine; HIV Clinical Trials Program

New Haven, Connecticut, 06501, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Holy Cross Hospital Inc

Fort Lauderdale, Florida, 33308, United States

Location

Larkin Community Hospital Palm Springs Campus (Hialeah)

Hialeah, Florida, 33012, United States

Location

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, 33136, United States

Location

Larkin Community Hospital

South Miami, Florida, 33143, United States

Location

St Luke's Health System; Rheumatology Research

Boise, Idaho, 83702, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118-2393, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Henry Ford Medical Center

Novi, Michigan, 48322, United States

Location

St. Michael'S Medical Center

Newark, New Jersey, 07102, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Wyckoff Heights Medical Center

Staten Island, New York, 11237, United States

Location

Novant Health Clinical Research

Charlotte, North Carolina, 28204, United States

Location

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

Location

Providence Saint Vincent's Medical Center

Portland, Oregon, 97225, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

The Liver Institute at Methodist Dallas

Arlington, Texas, 76012, United States

Location

Baylor Scott and White Medical Center - College Station

College Station, Texas, 77845, United States

Location

Baylor University Medical Center

Dallas, Texas, 75231, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital - HCHD

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Baylor Scott & White Medical Center - Irving

Irving, Texas, 75061, United States

Location

Baylor Scott & White Hospital - Plano

Plano, Texas, 75093, United States

Location

Baylor Scott & White Health

Temple, Texas, 76502, United States

Location

Intermountain LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

The Providence Regional Medical Center Everett

Everett, Washington, 98201, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia

Curitiba, Paraná, 80810-040, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ

Rio de Janeiro, Rio de Janeiro, 21045-900, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Instituto de Infectologia Emilio Ribas

São Paulo, São Paulo, 01246-000, Brazil

Location

Instituto do Coração - HCFMUSP

São Paulo, São Paulo, 05403-900, Brazil

Location

Medsi Clinic

Moscow, Adygeya Republic, 143442, Russia

Location

O.M. Filatov City Clinical Hospital #15; Department of Surgery

Moskva, Moscow Oblast, 111539, Russia

Location

City Pokrovskaya Hospital

Saint Petersburg, Sankt-Peterburg, 199106, Russia

Location

City Clinical Hospital # 52

Moscow, 123182, Russia

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas

Alcalá de Henares, Madrid, 28005, Spain

Location

Hospital Universitario HM Torrelodones

Torrelodones, Madrid, 28250, Spain

Location

Hospital General Universitario de Guadalajara

Guadalajara, 19002, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, 28040, Spain

Location

MeSH Terms

Interventions

remdesivir; tocilizumab

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann - La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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 28, 2020
• First Posted: June 1, 2020
• Study Start: June 16, 2020
• Primary Completion: February 1, 2021
• Study Completion: March 8, 2021
• Last Updated: February 14, 2022
• Results First Posted: February 14, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share

Locations

ES (5); US (38); BR (7); RU (4)