Tocilizumab plus Pembrolizumab in COVID-19

Phase 1

• Conditions: Coronavirus Disease 2019 (COVID-19)-Pneumonia; MedDRA version: 20.0Level: LLTClassification code 10051905Term: Coronavirus infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2020-001160-28-ES
• Lead Sponsor: Medica Scientia Innovation Research S.L. (MEDSIR)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-13
• Last Update Posted: 20 April 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Informed consent form (ICF) prior to participation in any study-related activities.
2.Male or nonpregnant female patients = 18 years and = 80 years at the time of ICF.
3.Laboratory confirmed COVID-19 infection defined with a positive RT-PCR from any specimen and/or detection of SARS-CoV-2 immunoglobulin (Ig)M/IgG antibodies.
4.Diagnostic confirmation of pneumonia by either chest X-ray or thoracic computed tomography (CT) scan (preferable).
5.Patient with acute respiratory syndrome related to COVID-19 under treatment as per hospital protocol during at least 48 hours.
6.Patients with SOFA score = 3 at the time of ICF.
7.Patients hospitalized with fever defined as temperature = 37,5 °C armpit.
8.Patients with total lymphocyte count =0,8 x106/mL.
9.Patients who are showing SpO2 = 92% on room air and/or patient who are showing SpO2 = 94% on room air and meet at least one of the following parameters:
•No objective clinical improvement at physician’s discretion after 48 hours of front-line standard care for COVID-19;
•Decrease in lymphocyte count (any decrease within 48 hours);
•Increase in ferritin levels (any increase within 48 hours);
•Increase in IL-6 levels (any increase within 48 hours);
•Increase in D-dimer levels (any increase within 48 hours);
•Increase in CRP levels (any increase within 48 hours);
•Increase in LDH levels (any increase within 48 hours);
•Increase in ESR levels (any increase within 48 hours).
10.Life expectancy greater than 10 days.
11.Willing to take study medication and to comply with all study procedures.
12.In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

1.Participation in any other clinical trial of an experimental treatment for COVID-19.
2.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.
3.Requiring endotracheal intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) at screening.
4.Patients being treated with immunomodulators or anti-rejection drugs.
5.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN).
6.Creatinine clearance < 50 mL/min.
7.Chronic Obstructive Pulmonary Disease (COPD) or end-stage lung disease that require home oxygen therapy.
8.Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation of study pembrolizumab and tocilizumab.
9.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.
10.Bowel diverticulitis or perforation.
11.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).
12.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).
13.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.
14.History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
15.Patients have any other concurrent severe medical condition that would, in the Investigator’s judgment contraindicate patient participation in the clinical study.
16.Pregnant women, lactating women and planned pregnant women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified