A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19.
Autor: | Seethamraju H; Montefiore Medical Center, Bronx, New York., Yang OO; David Geffen School of Medicine at UCLA, Los Angeles, California., Loftus R; Palmtree Clinical Research, Palm Springs, California., Ogbuagu O; Yale School of Medicine, New Haven, Connecticut., Sammartino D; White Plains Hospital, White Plains, New York., Mansour A; Montefiore Medical Center, Bronx, New York., Sacha JB; Oregon Health & Science University, Portland, Oregon., Ojha S; Oregon Health & Science University, Portland, Oregon., Hansen SG; Oregon Health & Science University, Portland, Oregon., Arman AC; CytoDyn Inc., Vancouver, Washington., Lalezari JP; Quest Clinical Research, San Francisco, California. Electronic address: drjay@questclinical.com. |
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Jazyk: | angličtina |
Zdroj: | Clinical therapeutics [Clin Ther] 2024 Nov; Vol. 46 (11), pp. 891-899. Date of Electronic Publication: 2024 Sep 30. |
DOI: | 10.1016/j.clinthera.2024.08.019 |
Abstrakt: | Purpose: Early in the course of the SARS-CoV-2 pandemic it was hypothesised that host genetics played a role in the pathophysiology of COVID-19 including a suggestion that the CCR5-Δ32 mutation may be protective in SARS-CoV-2 infection. Leronlimab is an investigational CCR5-specific humanized IgG4 monoclonal antibody currently in development for HIV-1 infection. We aimed to explore the impact of leronlimab on the severity of disease symptoms among participants with mild-to-moderate COVID-19. Methods: The TEMPEST trial was a randomized, double-blind, placebo-controlled study in participants with mild-to-moderate COVID-19. Participants were randomly assigned in a 2:1 ratio to receive subcutaneous leronlimab (700 mg) or placebo on days 0 and 7. The primary efficacy endpoint was assessed by change in total symptom score based on fever, myalgia, dyspnea, and cough, at end of treatment (day 14). Findings: Overall, 84 participants were randomized and treated with leronlimab (n = 56) or placebo (n = 28). No difference was observed in change in total symptom score (P = 0.8184) or other pre-specified secondary endpoints between treatments. However, in a post hoc analysis, 50.0% of participants treated with leronlimab demonstrated improvements from baseline in National Early Warning Score 2 (NEWS2) at day 14, compared with 20·8% of participants in the placebo group (post hoc; p = 0.0223). Among participants in this trial with mild-to-moderate COVID-19 adverse events rates were numerically but not statistically significantly lower in leronlimab participants (33.9%) compared with placebo participants (50.0%). Implications: At the time the TEMPEST trial was designed although CCR5 was known to be implicated in COVID-19 disease severity the exact pathophysiology of SARS-CoV-2 infection was poorly understood. Today it is well accepted that SARS-CoV-2 infection in asymptomatic-to-mild cases is primarily characterized by viral replication, with a heightened immune response, accompanied by diminished viral replication in moderate-to-severe disease and a peak in inflammatory responses with excessive production of pro-inflammatory cytokines in critical disease. It is therefore perhaps not surprising that no differences between treatments were observed in the primary endpoint or in pre-specified secondary endpoints among participants with mild-to-moderate COVID-19. However, the results of the exploratory post hoc analysis showing that participants in the leronlimab group had greater improvement in NEWS2 assessment compared to placebo provided a suggestion that leronlimab may be associated with a lower likelihood of people with mild-to-moderate COVID-19 progressing to more severe disease and needs to be confirmed in other appropriately designed clinical trials. Clinicaltrials: gov number, NCT04343651 https://classic. Clinicaltrials: gov/ct2/show/NCT04343651. Competing Interests: Declaration of competing interest O.O.Y. declares being on the scientific board and being a scientific consultant (compensated in stock options and cash) for CytoDyn and reports being co-founder and board member for CDR3 Therapeutics Corp (stock) as well as being on the Board of Directors for Applied Medical Inc (stock and cash). O.O. declares receiving honoraria from Gilead Sciences for advisory board membership. J.B.S. declares having a significant financial interest in and serves on the scientific advisory board of CytoDyn, a company that may have a financial interest in the results of this research and technology. This potential individual conflict of interest has been reviewed and managed by the Oregon Health & Science University. S.G.H. declares recieving compensation for consulting for CytoDyn. This potential conflict of interest has been reviewed and managed by the Oregon Health & Science University. C.A. and J.P.L. declares they are paid employees of CytoDyn and own stock. H.S., D.S., R.L., A.M., and S.O. declare that they have no known financial interests or personal relationships that could have appreared to influence the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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