A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

Giovanni Landoni; Lorenzo Piemonti; Antonella d'Arminio Monforte; Paolo Grossi; Alberto Zangrillo; Enrico Bucci; Marcello Allegretti; Giovanni Goisis; Elizabeth M Gavioli; Neal Patel; Maria De Pizzol; Georgea Pasedis; Flavio Mantelli

doi:10.1007/s40121-022-00644-6

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

Infect Dis Ther. 2022 Aug;11(4):1559-1574. doi: 10.1007/s40121-022-00644-6. Epub 2022 May 26.

Authors

Giovanni Landoni^#^{1

2}, Lorenzo Piemonti^#^{1

2}, Antonella d'Arminio Monforte³, Paolo Grossi⁴, Alberto Zangrillo^{1

2}, Enrico Bucci^{5

6}, Marcello Allegretti⁷, Giovanni Goisis⁷, Elizabeth M Gavioli⁷, Neal Patel⁷, Maria De Pizzol⁷, Georgea Pasedis⁷, Flavio Mantelli⁸

Affiliations

¹ IRCCS San Raffaele Scientific Institute, Milan, Italy.
² Vita-Salute San Raffaele University, Milan, Italy.
³ Ospedale San Paolo, Milan, Italy.
⁴ Ospedale di Varese, Varese, Italy.
⁵ Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA.
⁶ Resis Srl, Samone, Italy.
⁷ Dompé Farmaceutici SpA, Via Santa Lucia 6, 20122, Milan, Italy.
⁸ Dompé Farmaceutici SpA, Via Santa Lucia 6, 20122, Milan, Italy. Flavio.Mantelli@dompe.com.

^# Contributed equally.

Abstract

Introduction: Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer.

Methods: This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication.

Results: Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated.

Conclusion: In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results.

Trial registration: EudraCT identifier, 2020-001645-40; registered May 6, 2020 (retrospectively registered), and clinicaltrials.gov (NCT04794803) on March 8, 2021.

Keywords: COVID-19; CXCR1/2; IL-8; Reparixin; SARS-COV-2.

Associated data

ClinicalTrials.gov/NCT04794803