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Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial

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العنوان: Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial
المؤلفون: Seham Noureldin, David Smookler, Adam J. Gehring, Sergio Borgia, Andrea K. Boggild, Bryan Coburn, Ryan Hiebert, Janine McCready, Tiffany Chan, Muhammad Atif Zahoor, Atul Humar, Wesam Aleyadeh, Jeffrey S. Glenn, Christopher Kandel, Adrienne K. Chan, Julia Casey, Robert A. Kozak, Camille Lemieux, Bethany Barber, Henna Mistry, Ingrid Choong, Darrell H. S. Tan, D. Lorne Tyrrell, Colin Hislop, Rachel Hong, Jordan J. Feld, Deepali Kumar, Braden O’Neil, Anjali Patel, Harry L.A. Janssen, Bettina E. Hansen, Mia J. Biondi, Deanna M. Santer, Jeff Powis, Joshua Booth
المصدر: The Lancet. Respiratory Medicine
The Lancet Respiratory Medicine
سنة النشر: 2020
مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Placebo, Asymptomatic, Antiviral Agents, Severity of Illness Index, law.invention, Polyethylene Glycols, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Severity of illness, Clinical endpoint, Ambulatory Care, Medicine, Humans, 030212 general & internal medicine, Intention-to-treat analysis, business.industry, SARS-CoV-2, Interleukins, COVID-19, Articles, Middle Aged, Viral Load, Intention to Treat Analysis, Virus Shedding, COVID-19 Drug Treatment, Clinical trial, Treatment Outcome, 030228 respiratory system, RNA, Viral, Female, medicine.symptom, Drug Monitoring, business, Viral load
الوصف: Summary Background To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19. Methods In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ2 test following an intention-to-treat principle. Prespecified analysis of the primary endpoint, adjusted for baseline viral load, using bivariate logistic regression was done. The trial is now complete. This trial is registered with ClinicalTrials.gov, NCT04354259. Findings Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15–16·73; p=0·029). Of those with baseline viral load above 106 copies per mL, 15 (79%) of 19 patients in the peginterferon lambda group had undetectable virus on day 7, compared with six (38%) of 16 in the placebo group (OR 6·25 [95% CI 1·49–31·06]; p=0·012). Peginterferon lambda was well tolerated, and adverse events were similar between groups with mild and transient aminotransferase, concentration increases more frequently observed in the peginterferon lambda group. Two individuals met the threshold of grade 3 increase, one in each group, and no other grade 3 or 4 laboratory adverse events were reported. Interpretation Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding. Funding The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.
تدمد: 2213-2619
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0dc5c1b513da2a986e3a3832fbe0b50
https://pubmed.ncbi.nlm.nih.gov/33556319
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....b0dc5c1b513da2a986e3a3832fbe0b50
قاعدة البيانات: OpenAIRE
الوصف
تدمد:22132619