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
Overview
- Phase
- Phase 2
- Intervention
- Tocilizumab
- Conditions
- COVID-19
- Sponsor
- MedSIR
- Enrollment
- 12
- Locations
- 7
- Primary Endpoint
- Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-
- •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;
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Tocilizumab
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.
Intervention: Pembrolizumab (MK-3475)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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.)
- Evaluation of the radiological response(at days 1 and 28 (+/- 2 days))
- Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test(within 28 days from study inclusion)
- Number of days of patient hospitalization(through End of Study, defined as 90 ± 14 days after study entry)
- 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)
- Change from baseline of platelets(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- 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)
- Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of hemoglobin(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of creatinine(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of activated partial thromboplastin time (aPTT)(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of glucose(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of total bilirubin(days 3, 5, 7, 10, 14 and 28 after administration of study drug)
- Change from baseline of albumin(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)(Up to End of Study, defined as 90 ± 14 days after study entry)