Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial

BackgroundPharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFN beta -1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFN beta anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFN beta was indicated as the key component of a successful therapeutic combination.MethodsThis 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 IFN beta -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. IFN beta -1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48h 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 IFN beta -1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFN beta -1a in COVID-19 patients.DiscussionPotential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFN beta -1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFN beta -1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.Trial registrationEudraCT 2020-002458-25. Registered on May 11, 2020ClinicalTrials.gov Identifier: NCT04449380