Coronavirus Disease 2019 (COVID-19)-Pneumonia MedDRA version: 20.0 Level: LLT Classification code 10051905 Term: Coronavirus infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: KEYTRUDA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
Current Sponsor code: MK3475
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrat
Sponsors
Medica Scientia Innovation Research S.L. (MEDSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy –as determined by the proportion of patients with normalization of SpO2 =96%– of continued standard care together with tocilizumab plus pembrolizumab (MK-3475) in patients with COVID-19 pneumonia who are nonresponsive to frontline therapy within 48 hours from treatment initiation.;Secondary Objective: To assess the efficacy –as determined by: the proportion of patients with normalization of fever– of study drugs in this population. • the proportion of discharged patients– of study drugs in this population. • the duration of hospitalization– of study drugs in this population. • the Sequential Organ Failure Assessment (SOFA)– of study drugs in this population. • the mortality rate– of study drugs in this population. • the remission of respiratory symptoms– of study drugs in this population in terms of: -Time to invasive mechanical ventilation; -Time to independence from oxygen therapy. • the radiological response– of study drugs in this population. • the severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 negativization– of study drugs in this population. •the change in laboratory parameters– of study drugs in this population. •To evaluate the safety and tolerability of study drugs in this population.;Primary end point(s): Percentage of patients with normalization of SpO2 =96% through day 14 after study treatment initiation;Timepoint(s) of evaluation of this end point: through day 14 after study treatment initiation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Percentage of patients with temperature <37,5 °C armpit through hospital discharge. 2.Percentage of patients discharged from the hospital through end of study (EoS) (90 ± 14 days after study entry). 3.Number of days of hospitalization from baseline until EoS (90 ± 14 days after study entry ). 4.Change from baseline in SOFA score evaluated at day 1, 3, 5, 7, 14, 21, 28, and thereafter once weekly until hospital discharge only in case of an additional dosing. 5.Percentage of dead patients through EoS (90 ± 14 days after study entry ). 6.Remission of respiratory symptoms through EoS (90 ± 14 days after study entry ) in terms of: - Number of days of intubation; - Date of independence from oxygen therapy. 7.Change in radiological response from baseline to hospital discharge by using the same imaging technique. 8.Percentage of patients with SARS-CoV-2 negative result by reverse transcriptase - polymerase chain reaction (RT-PCR) at day 14 and on day of hospital discharge. 9.Change from baseline in both basic laboratory and inflammation parameters (see Appendix 1) at day 1, 3, 5, 7, 14, 21, 28, and thereafter once weekly until hospital discharge only in case of an additional dosing 10.Incidence of adverse events (AEs), incidence of prespecified AEs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 until EoS (90 ± 14 days after study entry).;Timepoint(s) of evaluation of this end point: 1.through hospital discharge. 2.through end of study (EoS) (90 ± 14 days after study entry). 3.from baseline until EoS (90 ± 14 days after study entry ). 4.Change from baseline in SOFA score evaluated at day 1, 3, 5, 7, 14, 21, 28, and thereafter once weekly until hospital discharge only in case of an additional dosing. 5. through EoS(90 ± 14 days after study entry). 6. through EoS(90 ± 14 days after study entry) 7.from baseline to hospital discharge by using the same imaging technique. 8. day 14 and on day of hospital di | — |
Countries
Spain
Contacts
Public ContactClinical Trial Unit
Medica Scientia Innovation Research S.L. (MEDSIR)
Outcome results
None listed