Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Checkpoint Blockade in COVID-19 Pandemic (COPERNICO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335305
Recruitment Status : Recruiting
First Posted : April 6, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
MedSIR

Tracking Information
First Submitted Date  ICMJE March 31, 2020
First Posted Date  ICMJE April 6, 2020
Last Update Posted Date November 27, 2020
Actual Study Start Date  ICMJE April 9, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2020)
Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes [ Time Frame: through day 14 after study treatment initiation ]
Assessed by hospital records
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
Percentage of patients with normalization of SpO2 ≥96% [ Time Frame: through day 14 after study treatment initiation ]
Assessed by hospital records
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2020)
  • Proportion of patients discharged from the emergency department and classified as low risk [ Time Frame: through End of Study, defined as 90 ± 14 days after study entry ]
    Assessed by hospital records
  • Number of days of patient hospitalization [ Time Frame: through End of Study, defined as 90 ± 14 days after study entry ]
    Assessed by hospital records
  • Change from baseline in organ failure parameters [ Time Frame: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first. ]
    The clinical status will be assessed by the SOFA scores
  • Proportion of mortality rate [ Time Frame: through End of Study, defined as 90 ± 14 days after study entry ]
    Determined as percentage of dead patients
  • Analysis of the remission of respiratory symptoms [ Time Frame: through End of Study, defined as 90 ± 14 days after study entry ]
    Determined as:
    • Time to invasive mechanical ventilation (if not previously initiated);
    • Time to independence from non-invasive mechanical ventilation;
    • Time to independence from oxygen therapy.
  • Evaluation of the radiological response [ Time Frame: at days 1 and 28 (+/- 2 days) ]
    by using the same imaging technique (chest X-ray or thoracic CT scan)
  • Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test [ Time Frame: within 28 days from study inclusion ]
    determined using oropharyngeal or anal swabs
  • Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of hemoglobin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of platelets [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of activated partial thromboplastin time (aPTT) [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of creatinine [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of glucose [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of total bilirubin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of albumin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability) [ Time Frame: Up to End of Study, defined as 90 ± 14 days after study entry ]
    Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
  • Proportion of patients with temperature < 37,5 °C armpit. [ Time Frame: through day 14 after study treatment initiation ]
    Assessed by hospital records
  • Proportion of patients discharged from the emergency department and classified as low risk [ Time Frame: In less than 28 days ]
    Assessed by hospital records
  • Change from baseline in organ failure parameters [ Time Frame: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first. ]
    The clinical status will be assessed by the SOFA scores
  • Proportion of mortality rate [ Time Frame: Day 28 ]
    Determined as percentage of dead patients
  • Analysis of the remission of respiratory symptoms [ Time Frame: Up to 3 months after last dose of treatment ]
    Determined as:
    • Time to invasive mechanical ventilation (if not previously initiated);
    • Time to independence from non-invasive mechanical ventilation;
    • Time to independence from oxygen therapy.
  • Evaluation of the radiological response [ Time Frame: at days 1 and 28 (+/- 2 days) ]
    by using the same imaging technique (chest X-ray or thoracic CT scan)
  • Time to first negative in SARS-CoV-2 RT-PCR test [ Time Frame: within 28 days from study inclusion ]
    determined using oropharyngeal or anal swabs
  • Change from baseline of ALC (absolute lymphocyte count),white blood cell count and white blood cell differential count [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of hemoglobin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of platelets [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of activated partial thromboplastin time (aPTT) [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of creatinine [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of glucose [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of total bilirubin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Change from baseline of albumin [ Time Frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug ]
    Baseline defined as the value collected at day 1, 2 hours before treatment administration
  • Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability) [ Time Frame: Up to 28 days after last dose of treatment ]
    Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Checkpoint Blockade in COVID-19 Pandemic
Official Title  ICMJE A Randomized, Controlled, Open-Label, Phase II Trial to Evaluate the Efficacy and Safety of Tocilizumab Combined With Pembrolizumab (MK-3475) in Patients With Coronavirus Disease 2019 (COVID-19)-Pneumonia
Brief Summary This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial
Detailed Description The aim of this study is to assess the efficacy -as determined by the proportion of patients with normalization of SpO2 ≥96% on room air- of continued standard care together with tocilizumab plus pembrolizumab (MK- 3475) in patients with COVID-19 pneumonia
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • COVID-19
  • Pneumonia, Viral
Intervention  ICMJE
  • Drug: Tocilizumab
    IV infusion over 60 minutes; 8 mg/kg (up to a maximum of 800 mg per dose); single dose
    Other Names:
    • Actemra
    • RoActemra
  • Biological: Pembrolizumab (MK-3475)
    IV infusion over 30 minutes, 200 mg; single dose
    Other Names:
    • MK-3475
    • Keytruda
Study Arms  ICMJE
  • Experimental: Tocilizumab plus Pembrolizumab (MK-3475)

    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.

    Interventions:
    • Drug: Tocilizumab
    • Biological: Pembrolizumab (MK-3475)
  • No Intervention: Continued Standard of Care
    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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 2, 2020)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.

  2. Male or non-pregnant female patients ≥ 18 years and ≤ 80 years at the time of ICF.
  3. 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.
  4. Diagnostic confirmation of pneumonia by either chest X-ray or thoracic CT scan (preferable).
  5. Patient with acute respiratory syndrome related to COVID-19.
  6. Patients with Sequential Organ Failure Assessment (SOFA) score ≤ 3 at the time of ICF.
  7. Patients with total lymphocyte count ≤0,8 x106/mL.
  8. 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.
  9. 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;
    • For patients on prior tocilizumab-containing regimen for COVID-19, no objective clinical improvement at physician's discretion within 48 hours after treatment initiation.
  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.

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 and/or tocilizumab.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alicia García +34 611 261 467 alicia.garcia@medsir.org
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04335305
Other Study ID Numbers  ICMJE MedOPP376
2020-001160-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedSIR
Study Sponsor  ICMJE MedSIR
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Javier Cortés IOB Institute of Oncology, Vall d´Hebron Institute of Oncology (VHIO)
PRS Account MedSIR
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP