Unit of Internal Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Trials. 2020 Nov 23;21(1):939. doi: 10.1186/s13063-020-04864-4.
Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.
This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.
Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.
EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.
目前仍缺乏经证实对 2019 年冠状病毒病（COVID-19）有效的药物治疗方法。我们发现 IFNβ-1a 是一种很有前途的药物，可用于治疗 COVID-19。其原理是基于 IFNβ 在体外对 SARS-CoV-2 的抗病毒活性以及与 SARS-CoV-2 感染相似的动物模型的证据，以及最近一项临床试验的结果，该试验表明 IFNβ 是成功治疗组合的关键成分。
这是一项随机、对照、开放标签、单中心、II 期试验（INTERCOP 试验）。126 例 SARS-CoV-2 拭子检测阳性、肺部影像学有肺炎征象、病情为轻至中度的患者将被随机分为 2:1 组，分别接受 IFNβ-1a 联合标准治疗和标准治疗。在对照组和干预组中都不会使用其他抗病毒药物。IFNβ-1a 将以 44 mcg（相当于 1200 万国际单位）的剂量皮下给药，每周 3 次，至少间隔 48 小时，总共给药 2 周。主要结局是 SARS-CoV-2 鼻咽拭子转阴的时间。次要结局包括使用 7 分制的临床严重程度评分（包括转入重症监护病房和死亡）、吸氧和无呼吸机天数、死亡率、肺部计算机断层扫描严重程度评分的变化、住院时间、鼻咽拭子病毒载量的降低、严重不良事件的数量以及器官功能障碍的生化标志物的变化。探索性结局包括血细胞计数、细胞因子和炎症特征、干扰素刺激基因的外周 mRNA 表达谱以及 SARS-CoV-2 和 IFNβ-1a 的抗体。INTERCOP 是第一项专门研究 IFNβ-1a 在 COVID-19 患者中的临床益处的研究。
该试验的潜在影响是多方面的：如果主要结局得到满足且治疗安全，人们可能会认为 IFNβ-1a 可用于降低轻度至中度疾病患者的传染性。如果 IFNβ-1a 缩短了住院时间和/或改善了临床状况，它可能成为 COVID-19 治疗的基石。
EudraCT 2020-002458-25。于 2020 年 5 月 11 日注册。ClinicalTrials.gov 标识符：NCT04449380。
