COVID-19Phase 2COPERNICONCT04335305
Checkpoint Blockade in COVID-19 Pandemic
A Phase 2 study testing Tocilizumab and Pembrolizumab (MK-3475) in people with COVID-19 and Pneumonia, Viral, run by MedSIR at 7 sites in Spain.
Trial summary
This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- COVID-19, Pneumonia, Viral
- What is being tested?
- Tocilizumab and Pembrolizumab (MK-3475)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 7 sitesSpain
- Study dates
- 9 Apr 2020to 21 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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;
- For patients on prior tocilizumab-containing regimen for COVID-19, no objective clinical improvement at physician's discretion within 48 hours after treatment initiation.
- Life expectancy greater than 10 days.
- Willing to take study medication and to comply with all study procedures.
- In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
Who cannot join
- 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.
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- 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.
- Patients have any other concurrent severe medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.
- Pregnant women, lactating women and planned pregnant women.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Spain7 sites
Hospital Quirónsalud Barcelona
Barcelona, 08023
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, 25198
Hospital Universitario Ramón y Cajal
Madrid, 280034
Hospital Ruber Juan Bravo
Madrid, 28006
Hospital Ruber Internacional
Madrid, 28036
Hospital Arnau de Vilanova-Lliria
Valencia, 46015
Hospital Universitario Doctor Peset
Valencia, 46017
About this study
Official title: 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
This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial
Read the 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
- Conditions
- COVID-19, Pneumonia, Viral
- Being tested
- Tocilizumab, Pembrolizumab (MK-3475)
- Medical subject headings
- COVID-19, Pneumonia, Viral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra, RoActemra
IV infusion over 60 minutes; 8 mg/kg (up to a maximum of 800 mg per dose); single dose
Pembrolizumab (MK-3475)Biological
Also called MK-3475, Keytruda
IV infusion over 30 minutes, 200 mg; single dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: through day 14 after study treatment initiation
Secondary outcomes (17)
Proportion of patients discharged from the emergency department and classified as low risk
Assessed by hospital records
Measured: through End of Study, defined as 90 ± 14 days after study entry
Number of days of patient hospitalization
Assessed by hospital records
Measured: through End of Study, defined as 90 ± 14 days after study entry
Change from baseline in organ failure parameters
The clinical status will be assessed by the SOFA scores
Measured: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.
Proportion of mortality rate
Determined as percentage of dead patients
Measured: through End of Study, defined as 90 ± 14 days after study entry
Analysis of the remission of respiratory symptoms
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.
Measured: through End of Study, defined as 90 ± 14 days after study entry
Evaluation of the radiological response
by using the same imaging technique (chest X-ray or thoracic CT scan)
Measured: at days 1 and 28 (+/- 2 days)
Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test
determined using oropharyngeal or anal swabs
Measured: within 28 days from study inclusion
Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of hemoglobin
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of platelets
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of activated partial thromboplastin time (aPTT)
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of creatinine
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of glucose
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of total bilirubin
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of albumin
Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measured: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability)
Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.
Measured: Up to End of Study, defined as 90 ± 14 days after study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start9 Apr 2020
- Primary completion8 Mar 2021
- Study completion21 Jun 2021
Why it stopped: Recruitment issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Cortés, Study chair, IOB Institute of Oncology, Vall d´Hebron Institute of Oncology (VHIO)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04335305
- Sponsor's protocol ID
- MedOPP376
- Other IDs
- 2020-001160-28
- Acronym
- COPERNICO
- Status last verified
- Jun 2022
- First submitted
- 31 Mar 2020
- Last updated
- 21 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04335305
- Acronym / sponsor ID
- COPERNICO / MedOPP376
- Conditions
- COVID-19, Pneumonia, Viral
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment issues
- Enrolment
- 12 participants (actual)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Study start
- 9 Apr 2020 (actual)
- Primary completion
- 8 Mar 2021 (actual)
- Study completion
- 21 Jun 2021 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab plus Pembrolizumab (MK-3475) | Experimental | Drug: Tocilizumab, Biological: 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. |
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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).
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: Actemra, RoActemraIV infusion over 60 minutes; 8 mg/kg (up to a maximum of 800 mg per dose); single dose | Drug | Tocilizumab plus Pembrolizumab (MK-3475) |
| Pembrolizumab (MK-3475)Also: MK-3475, KeytrudaIV infusion over 30 minutes, 200 mg; single dose | Biological | Tocilizumab plus Pembrolizumab (MK-3475) |
Primary outcome
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
17 secondary outcomes
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
Number of days of patient hospitalization
Time frame: through End of Study, defined as 90 ± 14 days after study entry
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.
Proportion of mortality rate
Time frame: through End of Study, defined as 90 ± 14 days after study entry
Analysis of the remission of respiratory symptoms
Time frame: through End of Study, defined as 90 ± 14 days after study entry
Evaluation of the radiological response
Time frame: at days 1 and 28 (+/- 2 days)
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
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
Change from baseline of hemoglobin
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of platelets
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of activated partial thromboplastin time (aPTT)
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
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
Change from baseline of creatinine
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of glucose
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of total bilirubin
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
Change from baseline of albumin
Time frame: days 3, 5, 7, 10, 14 and 28 after administration of study drug
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
Results and safety
The study was stopped early (reason given: Recruitment issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Cortés study chair
IOB Institute of Oncology, Vall d´Hebron Institute of Oncology (VHIO)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab and Pembrolizumab (MK-3475) in people with COVID-19 and Pneumonia, Viral, run by MedSIR at 7 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment issues). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2022.