Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

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Journal
Microorganisms
Published
2024-08-26
DOI
https://doi.org/10.3390/microorganisms12091767
Citations
5
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
1.56
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article

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements

Benjamín Valente-Acosta, Krzysztof Simon, Natalia A. Bakhtina, Guido Chichino et al.
5 citations
Microorganisms
COVID-19 Clinical Research Studies
1.56
article

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements

Benjamín Valente-Acosta, Krzysztof Simon, Natalia A. Bakhtina, Guido Chichino, Ofra Barnett‐Griness, Alexey Klinov, Tatiana Martynenko, Jose Oñate-Gutierrez, Giuliano Rizzardini, Ivan Shishimorov, Adam Barczyk, Eduardo Sprinz, Gina Eagle, Vered Katz Ben-Yair, S. V. Zhuravel, Anastasia Ivanova, Aida Bibliowicz, Walter Gabriel Chaves, Rogério Sobroza de Mello, Adam Fronczak, Amer Saffoury, Patricia J. Anderson, Michal Klein, В. А. Мартынов, Yu. G. Shvarts, ‪Yasmin Maor‬‏, Piotr Blewaska, Janaina Pilau, Ami Mayo, Rachael L. Gerlach, Oleg O. Burlaka, Nimer Assy, Maskit Bar‐Meir, Eppie Campbell, Mark L. Levitt, Conrado Roberto Hoffmann Filho, Galina Yurevna Trufanova, N. V. Lomakin, Boris Mikhailovich Goloshchekin, Fernando Carvalho Neuenschwander, Sergio Saul Irizar Santana, Ewelina Nahorecka, Jacek Wróblewski, Ludhmila Abrahão Hajjar, Clara Fehrmann, Adilson Joaquim Westheimer Calvacante, Oleg Khmelnitskiy, Stefania Piconi, Gilead Raday, Ana Carolina Nazare de Mendonca Procopio, Andres Felipe Ocampo Agudelo, Cristian Iván García Rincón, Osama Hussein, Stefano Bonora, Reza Fathi
article en
5 citations

Abstract

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

MicroorganismsVol. 12(9)
Israel Institute for Biological Research (IL), Volgograd State Medical University (RU), Tel Aviv University (IL), Medical University of Silesia (PL), Universidad Pontificia Bolivariana (CO), Western Galilee Hospital (IL), Nazareth Hospital EMMS (IL), Assuta Medical Center (IL), Wolfson Medical Center (IL), Shaare Zedek Medical Center (IL), Rebecca Sieff Hospital (IL), Hospital Universitario de San Vicente Fundación (CO), Luigi Sacco Hospital (IT), Murmansk Regional Clinical Hospital (RU), Hospital Ortopédico de Passo Fundo (BR), Wojewódzki Szpital Specjalistyczny we Wrocławiu (PL), Saratov Research Institute of Traumatology and Orthopedics (RU), Hospital Felício Rocho (BR), Hospital de Clínicas de Porto Alegre (BR), Pediatric Hospital of Sinaloa (MX), Research Institute of Emergency Care (RU), St. Petersburg State Medical Academy "City Hospital No. 26" (RU), Russian Medical Academy of Continuous Professional Education (RU), City Hospital No. 40 (RU), Ospedale Amedeo di Savoia (IT), Alessandro Manzoni Hospital (IT), Caucaseco Scientific Research Center (CO), Hospital Nossa Senhora da Conceição (BR), Ministry of Health of the Russian Federation (RU), Kirov State Medical Academy (RU), Budgetary Healthcare Institution of Omsk Region Regional Clinical Hospital (RU), Centro Médico ABC (MX), Centrum Onkologii (PL), Wojewódzki Szpital Zespolony (PL), Regional Public Health Care Institution "City Hospital No. 5, Barnaul" (RU), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Państwowa Wyższa Szkoła Zawodowa w Raciborzu (PL)
Good health and well-being
Openalex Percentile: Top 17%
COVID-19 Clinical Research Studies
1.56
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