NCT04335305终止2 期
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
MedSIR7 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2020年4月9日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 7
- 主要终点
- Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes
研究概览
简要总结
This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •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.
- •Exclusion criteria
- •Participation in any other clinical trial of an experimental treatment for COVID-
- •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.
- •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.
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Tocilizumab (Drug)
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.
干预措施: Pembrolizumab (MK-3475) (Biological)
结局指标
主要结局
Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes
时间窗: through day 14 after study treatment initiation
Assessed by hospital records
次要结局
- 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)
研究者
研究点 (7)
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