Clinical Trial to Evaluate the Effectiveness and Safety of Tocilizumab for Treating Patients With COVID-19 Pneumonia

NCT ID: NCT04445272

Last Updated: 2021-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 495 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-22
• Study Completion Date: 2020-12-23

Brief Summary

At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia.

The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.

Detailed Description

Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an exaggerated immune response. CSS can be triggered by infections or therapeutic interventions, being more severe depending on the degree and duration of immune activation. CSS is as a significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which have been subject to assessment for the treatment of haematological malignancies. Tocilizumab (intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T cell-induced severe or life-threatening CSS.

Based on the experience with tocilizumab in the CSS, and that some patients infected with SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is being investigated in China and Italy, and clinical trials are being conducted/planned in these and several other countries. Real-word experience with tocilizumab IV have shown that in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to normal and respiratory function based on oxygen intake and lung opacities improved remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased in patients infected decreased significantly with tocilizumab, and lymphocytes levels also returned to normal.

All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to initiate the controlled distribution of tocilizumab IV, in light of the increased interest on the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore, tocilizumab might be among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients.

The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU. This large real-world cohort provides a unique opportunity to study a potential medicine during the current emergency situation, and support the findings from the Roche-sponsored Phase III study that is planned to start in early April.

Conditions

COVID-19

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab

Patients will receive IV tocilizumab as per clinical practice and at the discretion of treating investigator, following the posology indicated in the SmPC, or the recommendations proposed by the Spanish Ministry of Health:

The recommended posology by the SmPC is 8 mg per kg in patients weighing greater than or equal to 30 kg or 12 mg per kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours.

The recommendations of the Spanish Ministry of Health:

Patients more than 80 kg: first dose 600 mg; second dose 600 mg. Patients less than 80 kg: first dose 600 mg; second dose 400 mg.

A third dose might be considered 16 to 24 hours after if: fever persists or a worsening of the laboratory parameters

Given the exceptionality of the situation modification of doses according to the physician experience will be allowed.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Treatment with Tocilizumab

Interventions

Tocilizumab

Treatment with Tocilizumab

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provide oral informed consent to participate in this study.
• At least 18 years of age.
• Diagnosed with COVID-19 pneumonia by RT-PCR.
• Have received the first dose of tocilizumab a maximum of two days before the inclusion or is candidate for tocilizumab treatment
• Hospitalized or admitted to ICU

Exclusion Criteria

• The patient has any other medical condition or is receiving concomitant medication that could, in the opinion of the investigator, compromise the patient's safety or collected data
• Known severe allergic reactions to tocilizumab or other monoclonal antibodies
• Active acute and severe infections, including tuberculosis infection
• Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Dynamic Science S.L.

INDUSTRY

Sponsor Role: collaborator

Fundacion SEIMC-GESIDA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose Antonio Pérez Molina

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Ramón y Cajal

Locations

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Sant Joan de Déu de Manresa

Manresa, Barcelona, Spain

Hospital de Mataró

Mataró, Barcelona, Spain

Hospital Universitario de Galdakao

Galdakao, Bizkaia, Spain

Hospital Universitario Marqués Valdecilla

Santander, Cantabria, Spain

Hospital Público General del Tomelloso

Tomelloso, Ciudad Real, Spain

Hospital Jerez de la Frontera

Jerez de la Frontera, Cádiz, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, Spain

Hospital Universitario de Getafe

Getafe, Madrid, Spain

Hospital Rey Juan Carlos

Móstoles, Madrid, Spain

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, Spain

Hospital Universitario Infanta Sofía

San Sebastián de los Reyes, Madrid, Spain

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Hospital Universitario de Cabueñes

Gijón, Principality of Asturias, Spain

Hospital Nuestra Señora del Prado

Talavera de la Reina, Toledo, Spain

Complejo Hospitalario Universitario de Albacete

Albacete, , Spain

Hospital Infanta Cristina

Badajoz, , Spain

Hospital Clínic i Provincial Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario de Burgos

Burgos, , Spain

Hospital Universitario Dr. Josep Trueta

Girona, , Spain

Hospital Universitario Clínico San Cecilio

Granada, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Universitario Infanta Leonor

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, , Spain

Complexo Hospitalario Universitario de Ourense

Ourense, , Spain

Hospital Universitario Salamanca

Salamanca, , Spain

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitari i Poliectenic La Fe

Valencia, , Spain

Hospital Universitario Dr. Peset

Valencia, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014 Mar-Apr;20(2):119-22. doi: 10.1097/PPO.0000000000000035.

Reference Type: BACKGROUND

PMID: 24667956 (View on PubMed)

Other Identifiers

BREATH-19 (FSG011-20)

Identifier Type: -

Identifier Source: org_study_id