Browsing by Author "Fish, Eleanor"

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    Interferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial
    (Elsevier Ltd, 2023) Castro Rodríguez, José Antonio; Fish, Eleanor; Montgomery, Samuel T.; Kollmann, Tobias R.; Iturriaga Ortiz, Carolina Alejandra; Shannon, Casey; Karpievitch, Yuliya; Ho, Joseph; Chen, Virginia; Balshaw, Robert; Ben-Othman, Rym; Aniba, Radhouane; Gidi Yunge, Francisca Andrea; Hartnell, Lucy; Hancock, David G.; Perez Mateluna, Guillermo Andrés; Urzua, Marcela; Tebbutt, Scott J.; Garcia-Huidobro, Munita Diego Nicolas; Perret, Perez Cecilia; Borzutzky Schachter, Arturo José; Stick, Stephen M.
    © 2023 The Author(s)Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = −0.2%, 95% CI = −8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = −3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as ‘Plegridy (peginterferon beta-1a).’ The study was substantially funded by BHP Holdings Pty Ltd.
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    Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-& alpha;2b in Healthy Adults: The (INCOVID)-C-2 Phase I Randomized Trial
    (2023) García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Fajuri, Paula; Severino Cuevas, Nicolás Felipe; Urzua, Marcela; Fraga, Juan Pablo; Cruz, Javiera de la; Poli, Cecilia; Castro Rodríguez, José Antonio; Fish, Eleanor; Borzutzky, Arturo
    Background and ObjectivesInterferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-& alpha;2b (IFN)-& alpha;2b in healthy adults.MethodsA double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-& alpha;2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-& alpha;2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFN & alpha; concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.ResultsExposure to inhaled IFN-& alpha;2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-& alpha; concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).ConclusionsInhaled IFN-& alpha;2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.