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Efficacy and Safety of Danirixin (GSK1325756) Co-administered With Standard-of-Care Antiviral (Oseltamivir): A Phase 2b, Global, Randomized Study of Adults Hospitalized With Influenza
- Source :
- Open Forum Infectious Diseases
- Publication Year :
- 2019
- Publisher :
- Oxford University Press, 2019.
-
Abstract
- Background Excessive neutrophil migration has been correlated with influenza symptom severity. Danirixin (GSK1325756), a selective and reversible antagonist of C-X-C chemokine receptor 2, decreases neutrophil activation and transmigration to areas of inflammation. This study evaluated the efficacy and safety of intravenous (IV) danirixin co-administered with oseltamivir for the treatment of adults hospitalized with influenza. Methods In this phase 2b, double-blind, 3-arm study (NCT02927431), influenza-positive participants were randomized 2:2:1 to receive danirixin 15mg intravenously (IV) twice daily (bid) + oral oseltamivir 75mg bid (OSV), danirixin 50mg IV bid + OSV, or placebo IV bid + OSV, for up to 5 days. The primary endpoint was time to clinical response (TTCR). Results In total, 10 participants received study treatment (danirixin 15mg + OSV, n = 4; danirixin 50mg + OSV, n = 4; placebo + OSV, n = 2) before the study was terminated early due to low enrollment. All participants achieved a clinical response. Median (95% confidence interval) TTCR was 4.53 days (2.95, 5.71) for danirixin 15mg + OSV, 4.76 days (2.71, 5.25) for danirixin 50mg + OSV, and 1.33 days (0.71, 1.95) for placebo + OSV. Adverse events (AEs) were generally of mild or moderate intensity; no serious AEs were considered treatment-related. Interleukin-8 levels increased in nasal samples (using synthetic absorptive matrix strips) and decreased serum neutrophil-elastase–mediated degradation of elastin decreased in danirixin-treated participants, suggesting effective target engagement. Conclusions Interpretation of efficacy results is restricted by the low participant numbers. The safety and tolerability profile of danirixin was consistent with previous studies. Clinical trial information The registration data for the trial are in the ClinicalTrials.gov database, number NCT02927431, and in the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/) as GSK study 201023, EudraCT 2016-002512-40. Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.<br />In this phase 2b, randomized, placebo-controlled study of intravenous danirixin in hospitalized influenza patients, all participants achieved a clinical response; danirixin had an acceptable safety profile. Early termination due to low recruitment and small sample size limits interpretation.
- Subjects :
- 0301 basic medicine
Oseltamivir
medicine.medical_specialty
030106 microbiology
Placebo
law.invention
Major Articles
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
neutrophils
law
Internal medicine
medicine
Clinical endpoint
030212 general & internal medicine
Adverse effect
business.industry
Confidence interval
Clinical trial
Infectious Diseases
Oncology
chemistry
Tolerability
CXCR2 antagonist
danirixin
business
influenza
hospitalization
Subjects
Details
- Language :
- English
- ISSN :
- 23288957
- Volume :
- 6
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Open Forum Infectious Diseases
- Accession number :
- edsair.doi.dedup.....7cd2ee6bdf4a1dd77252a6e6a1f1dda1