TY - JOUR
T1 - Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP)
T2 - study protocol for a randomized controlled trial
AU - Bosi, Emanuele
AU - Bosi, Carlo
AU - Rovere Querini, Patrizia
AU - Mancini, Nicasio
AU - Calori, Giliola
AU - Ruggeri, Annalisa
AU - Canzonieri, Cecilia
AU - Callegaro, Luciano
AU - Clementi, Massimo
AU - De Cobelli, Francesco
AU - Filippi, Massimo
AU - Bregni, Marco
N1 - Funding Information:
The authors read and approved the final manuscript. EB is the principal investigator; he and CB conceived the study and wrote the manuscript. MF is the co-principal investigator. EB, CB, LC, PRQ, NM, MF, and MB contributed to the protocol design. NM and MC worked on the virologic outcomes. FDC contributed the radiological outcome. GC and AR provided the statistical plan. CC provided support on the regulatory aspects of the trial. The authors declare that they have no competing interests. The sponsor of the trial will be the IRCCS Ospedale San Raffaele. A contract between IRCCS Ospedale San Raffaele (via Olgettina, 60 ? Milano) and Merck Serono S.p.A. assigned a grant to cover the costs of drug (Rebif?) supply and delivery. All relevant data will be included in the article. Additional information is available from the corresponding author on reasonable request. This protocol and the template informed consent forms have been reviewed and approved by the Central Ethics Committee INMI ?Lazzaro Spallanzani? ? Rome, acting as Central IRB for clinical trials pertaining COVID-19 in Italy: approval number: no. 161/2020. As this is a study with medicinal products, also the Italian Drug Agency?Agenzia Italiana del Farmaco (AIFA)?authorized the clinical trial on June 19, 2020. Written informed consent to participate will be obtained from all study participants.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Background: 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. Methods: 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. Discussion: 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. Trial registration: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380
AB - Background: 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. Methods: 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. Discussion: 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. Trial registration: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380
KW - COVID-19
KW - IFNβ-1a
KW - SARS-CoV-2
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U2 - 10.1186/s13063-020-04864-4
DO - 10.1186/s13063-020-04864-4
M3 - Article
C2 - 33225960
AN - SCOPUS:85096430310
VL - 21
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 939
ER -