Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN
Journal
Clinical drug investigation
ISSN: 1179-1918
Titre abrégé: Clin Drug Investig
Pays: New Zealand
ID NLM: 9504817
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
accepted:
28
05
2023
medline:
29
6
2023
pubmed:
22
6
2023
entrez:
22
6
2023
Statut:
ppublish
Résumé
Interferons 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-α2b (IFN)-α2b in healthy adults. A 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-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b 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 IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. Exposure to inhaled IFN-α2b 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-α 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). Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Interferons 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-α2b (IFN)-α2b in healthy adults.
METHODS
METHODS
A 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-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b 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 IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.
RESULTS
RESULTS
Exposure to inhaled IFN-α2b 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-α 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).
CONCLUSIONS
CONCLUSIONS
Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.
CLINICAL TRIAL REGISTRATION
BACKGROUND
The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.
Identifiants
pubmed: 37347370
doi: 10.1007/s40261-023-01278-3
pii: 10.1007/s40261-023-01278-3
doi:
Substances chimiques
Interferon-alpha2b
0
Interferon-alpha
0
Interferon alpha-2
0
Banques de données
ClinicalTrials.gov
['NCT04988217']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
447-461Investigateurs
Juan Pablo Olivo
(J)
Katherine Suisbert
(K)
Andrea Cruz
(A)
Katterine Perez
(K)
Romina Valdivieso
(R)
Diego Navarro
(D)
Francisco Pereira
(F)
Vanessa Monge
(V)
Marisol Dibarrart
(M)
Krisbeth Salazar
(K)
Morgan Bracho
(M)
Lidia Pontanilla
(L)
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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