tetano
Editor, Senior Moderator
PLoS One
. 2024 Feb 23;19(2):e0299197.
doi: 10.1371/journal.pone.0299197. eCollection 2024. Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial
Bruno Martins Tomazini[SUP] 1 2 3 [/SUP], Lucas Tramujas[SUP] 1 [/SUP], Fernando Azevedo Medrado Junior[SUP] 1 [/SUP], Samara Pinheiro do Carmo Gomes[SUP] 1 [/SUP], Karina Leal Negrelli[SUP] 1 [/SUP], Gabriela Souza Murinize[SUP] 1 [/SUP], Renato Hideo Nakagawa Santos[SUP] 1 [/SUP], Bruna Martins Pereira Vianna[SUP] 1 [/SUP], Bruna Fornazieri Piotto[SUP] 1 [/SUP], Thabata Silva Veiga[SUP] 1 [/SUP], Bianca Rodrigues do Santos[SUP] 1 [/SUP], Ana Clara Peneluppi Horak[SUP] 1 [/SUP], Olivia Mora Cavalcante Lemos[SUP] 4 [/SUP], Marcela de Almeida Lopes[SUP] 1 [/SUP], Beatriz Baptista Olicheski[SUP] 4 [/SUP], Diego Lurentt Campones[SUP] 4 [/SUP], Luiz Angelo Alencar Peixoto[SUP] 4 [/SUP], Aline Dos Anjos Chaves Basilio[SUP] 4 [/SUP], Otavio Celso Eluf Gebara[SUP] 5 [/SUP], Ana Tarina Alvarez Lopes[SUP] 5 [/SUP], Humberto Saconato[SUP] 5 [/SUP], Nanci Valeis[SUP] 1 [/SUP], Tamiris Abait Miranda[SUP] 1 [/SUP], Ligia Nasi Laranjeira[SUP] 1 [/SUP], Eliana Vieira Santucci[SUP] 1 [/SUP], Aaron Foster Carlin[SUP] 6 [/SUP], Jeffrey David Esko[SUP] 7 [/SUP], Phillip Leo Stephan Marie Gordts[SUP] 8 [/SUP], Sotirios Tsimikas[SUP] 9 [/SUP], Alexandre Biasi Cavalcanti[SUP] 1 2 [/SUP]
Affiliations
Background: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.
Methods: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.
Results: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.
Conclusions: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.
. 2024 Feb 23;19(2):e0299197.
doi: 10.1371/journal.pone.0299197. eCollection 2024. Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial
Bruno Martins Tomazini[SUP] 1 2 3 [/SUP], Lucas Tramujas[SUP] 1 [/SUP], Fernando Azevedo Medrado Junior[SUP] 1 [/SUP], Samara Pinheiro do Carmo Gomes[SUP] 1 [/SUP], Karina Leal Negrelli[SUP] 1 [/SUP], Gabriela Souza Murinize[SUP] 1 [/SUP], Renato Hideo Nakagawa Santos[SUP] 1 [/SUP], Bruna Martins Pereira Vianna[SUP] 1 [/SUP], Bruna Fornazieri Piotto[SUP] 1 [/SUP], Thabata Silva Veiga[SUP] 1 [/SUP], Bianca Rodrigues do Santos[SUP] 1 [/SUP], Ana Clara Peneluppi Horak[SUP] 1 [/SUP], Olivia Mora Cavalcante Lemos[SUP] 4 [/SUP], Marcela de Almeida Lopes[SUP] 1 [/SUP], Beatriz Baptista Olicheski[SUP] 4 [/SUP], Diego Lurentt Campones[SUP] 4 [/SUP], Luiz Angelo Alencar Peixoto[SUP] 4 [/SUP], Aline Dos Anjos Chaves Basilio[SUP] 4 [/SUP], Otavio Celso Eluf Gebara[SUP] 5 [/SUP], Ana Tarina Alvarez Lopes[SUP] 5 [/SUP], Humberto Saconato[SUP] 5 [/SUP], Nanci Valeis[SUP] 1 [/SUP], Tamiris Abait Miranda[SUP] 1 [/SUP], Ligia Nasi Laranjeira[SUP] 1 [/SUP], Eliana Vieira Santucci[SUP] 1 [/SUP], Aaron Foster Carlin[SUP] 6 [/SUP], Jeffrey David Esko[SUP] 7 [/SUP], Phillip Leo Stephan Marie Gordts[SUP] 8 [/SUP], Sotirios Tsimikas[SUP] 9 [/SUP], Alexandre Biasi Cavalcanti[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38394069
- PMCID: PMC10889621
- DOI: 10.1371/journal.pone.0299197
Background: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.
Methods: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.
Results: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.
Conclusions: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.