Checkpoint Blockade in COVID-19 Pandemic

NCT04335305 | Terminated Phase 2

• 2 other identifiers: MedOPP3762020-001160-28
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial

Conditions

COVID-19; Pneumonia, Viral

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes

  Assessed by hospital records

  through day 14 after study treatment initiation

Secondary Outcomes (17)

• Proportion of patients discharged from the emergency department and classified as low risk

  through End of Study, defined as 90 ± 14 days after study entry

• Number of days of patient hospitalization

  through End of Study, defined as 90 ± 14 days after study entry

• Change from baseline in organ failure parameters

  Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.

• Proportion of mortality rate

  through End of Study, defined as 90 ± 14 days after study entry

• Analysis of the remission of respiratory symptoms

  through End of Study, defined as 90 ± 14 days after study entry

Study Arms (2)

Tocilizumab plus Pembrolizumab (MK-3475)

EXPERIMENTAL

Tocilizumab 8 mg/kg (up to a maximum of 800 mg per dose) as an intravenous infusion over 60 minutes; single dose Pembrolizumab (MK3475) 200 mg as an intravenous infusion over 30 minutes; single dose. Patients who are showing no clinical improvement in respiratory function after 12 hours could receive an additional dose of tocilizumab at the same dose level of the first administration. Patients who are showing SpO2 ≤ 94% on room air could receive an additional administration of pembrolizumab (MK-3475) at the same recommended dose after 3 weeks from treatment initiation and/or an additional dose of tocilizumab after 4 weeks from treatment initiation at physician's discretion.

Drug: Tocilizumab; Biological: Pembrolizumab (MK-3475)

Continued Standard of Care

NO INTERVENTION

Standard care per local written policies or guidelines comprises, as necessary and at physician's discretion, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, glucocorticoid, tocilizumab, virally targeted agents, chloroquine or hydroxychloroquine.

Interventions

Tocilizumab DRUG

IV infusion over 60 minutes; 8 mg/kg (up to a maximum of 800 mg per dose); single dose

Also known as: Actemra, RoActemra

Tocilizumab plus Pembrolizumab (MK-3475)

Pembrolizumab (MK-3475) BIOLOGICAL

IV infusion over 30 minutes, 200 mg; single dose

Also known as: MK-3475, Keytruda

Tocilizumab plus Pembrolizumab (MK-3475)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent form (ICF) prior to participation in any study-related activities.
• Note: If no written ICF can be provided by the trial participant, consent could be given either orally in the presence of an impartial witness or from the legal representative in accordance with national and local patient regulations.
• Male or non-pregnant female patients ≥ 18 years and ≤ 80 years at the time of ICF.
• Laboratory confirmed COVID-19 infection defined with a positive reverse transcription-polymerase chain reaction (RT-PCR) from any specimen and/or detection of SARS-CoV-2 immunoglobulin (Ig)M/IgG antibodies.
• Diagnostic confirmation of pneumonia by either chest X-ray or thoracic CT scan (preferable).
• Patient with acute respiratory syndrome related to COVID-19.
• Patients with Sequential Organ Failure Assessment (SOFA) score ≤ 3 at the time of ICF.
• Patients with total lymphocyte count ≤0,8 x106/mL.
• Patients who are showing SpO2 ≤ 92% on room air (measured without any respiratory support for at least 15 minutes). Note: For patients on prior tocilizumab-containing regimen, SpO2 ≤ 94% on room air is sufficient criterion for their eligibility.
• Patients who meet at least one of the following parameters: • Increased levels of ferritin;
• Increased levels of IL-6;
• Increased levels of D-dimer;
• Increased levels of CRP;
• Increased levels of LDH;
• Increased levels of ESR;

You may not qualify if:

• Participation in any other clinical trial of an experimental treatment for COVID-19.
• Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited \< 24 hours prior to study drug dosing, except the commonly used antiviral drugs and/or chloroquine and/or tocilizumab.
• Requiring endotracheal intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) at screening.
• Patients being treated with immunomodulators or anti-rejection drugs.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN).
• Creatinine clearance \< 50 mL/min.
• Chronic Obstructive Pulmonary Disease (COPD) or end-stage lung disease that require home oxygen therapy.
• Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation of study pembrolizumab and tocilizumab.
• Treatment with high doses of systemic corticosteroids within 72 hours prior obtaining consent except for inhaled steroids and prior corticosteroid therapy at dose lower than or equal to 10 mg/day methylprednisolone equivalent.
• Bowel diverticulitis or perforation.
• Diagnosis of immunodeficiency receiving immunosuppressive therapy within seven days prior to study treatment initiation. Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if PCR test is negative for HCV ribonucleic acid (RNA).
• Vaccination with any live virus vaccine within 28 days prior to study treatment initiation.
• Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live-attenuated vaccines and are not allowed.
• History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.

Sponsors & Collaborators

• MedSIR: lead

Study Sites (7)

Hospital Quirónsalud Barcelona

Barcelona, 08023, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 280034, Spain

Location

Hospital Ruber Juan Bravo

Madrid, 28006, Spain

Location

Hospital Ruber Internacional

Madrid, 28036, Spain

Location

Hospital Arnau de Vilanova-Lliria

Valencia, 46015, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral

Interventions

tocilizumab; pembrolizumab

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Javier Cortés

  IOB Institute of Oncology, Vall d´Hebron Institute of Oncology (VHIO)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 6, 2020
• Study Start: April 9, 2020
• Primary Completion: March 8, 2021
• Study Completion: June 21, 2021
• Last Updated: June 21, 2022

Record last verified: 2022-06

Locations

ES (7)