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1.
Vaccine ; 42(17): 3699-3709, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38734495

RESUMO

Clinical trials of new vaccines based on existing variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are often impacted by the emergence of new virus variants. We evaluated the efficacy, immunogenicity, and safety of S-268019-b, a recombinant spike protein subunit vaccine based on the ancestral strain, for preventing symptomatic coronavirus disease 2019 (COVID-19) during the Omicron (BA.2)-dominant period in Vietnam. In this multicentre, phase 3, randomised (2:1), observer-blind, placebo-controlled crossover study, participants received 2 intramuscular doses (28 days apart) of either 10 µg of S-268019-b (Recombinant S-protein vaccine) or placebo. The primary endpoint was incidence of laboratory-confirmed symptomatic COVID-19 before crossover, with onset within 14 days following the second dose, in participants who were seronegative and reverse transcription polymerase chain reaction (RT-PCR)-negative at baseline. The secondary endpoints included immunogenicity and safety. In total, 8,594 participants were randomised (S-268019-b [n = 5,727]; placebo [n = 2,867]). Vaccine efficacy versus placebo was 39·1 % (95 % confidence interval [CI]:26·6-49·5; one-sided P = 0·0723). The incidence rate (95 % CI) of symptomatic COVID-19 was 776·41/1,000 person-years (682·04-880·19) in the S-268019-b group and 1272·87/1,000 person-years (1101·32-1463·57) in the placebo group. The geometric mean titres (95 % CI) of the SARS-CoV-2 neutralising antibody increased on Day 57 versus baseline with S-268019-b (34·66 [27·04-44·41] versus 2·50 (non-estimable) but not with placebo. There were no safety concerns regarding S-268019-b. S-268019-b did not demonstrate the targeted efficacy threshold against symptomatic COVID-19; however, findings were comparable with other prophylactic vaccines based on ancestor strain during the Omicron-dominant period. S-268019-b demonstrated immunogenicity and was well-tolerated. ClinicalTrials.gov identifier: NCT05212948.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas Sintéticas , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Feminino , Adulto , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vietnã , Adulto Jovem , Estudos Cross-Over , Adolescente , Eficácia de Vacinas , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas de Subunidades Antigênicas
2.
Antivir Ther ; 22(4): 313-323, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27805571

RESUMO

BACKGROUND: Intravenous peramivir is a potent neuraminidase (NA) inhibitor with activity against influenza A and B viruses. The early use of NA inhibitors has been shown to reduce mortality in influenza patients. METHODS: To evaluate the pharmacokinetics of peramivir and confirm the safety and tolerability of multiple infusions of peramivir in healthy Japanese subjects, two Phase I, single-centre, randomized, double-blind and placebo-controlled studies consisting of a multiple-dose study and a high-dose study were conducted. RESULTS: Multiple intravenous infusions of peramivir were well tolerated up to 800 mg once a day and 400 mg twice daily for 6 days. Dose proportionalities for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were established up to the 800 mg dose. Approximately 90% of unchanged peramivir was excreted into urine within 12 h after treatment with 800 mg of peramivir. The peramivir plasma and upper respiratory tract fluid levels were significantly higher than the 50% inhibition concentrations for NA enzyme activity (IC50) of epidemic influenza viruses, including those harbouring the H274Y mutation. CONCLUSIONS: The pharmacokinetic properties obtained here for intravenous peramivir are consistent with the previously reported clinical efficacy and safety of this antiviral.


Assuntos
Antivirais/farmacocinética , Ciclopentanos/farmacocinética , Inibidores Enzimáticos/farmacocinética , Guanidinas/farmacocinética , Ácidos Carbocíclicos , Administração Intravenosa , Adulto , Antivirais/sangue , Área Sob a Curva , Ciclopentanos/sangue , Método Duplo-Cego , Esquema de Medicação , Inibidores Enzimáticos/sangue , Feminino , Expressão Gênica , Guanidinas/sangue , Voluntários Saudáveis , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/enzimologia , Influenza Humana/tratamento farmacológico , Masculino , Neuraminidase/antagonistas & inibidores , Neuraminidase/genética , Neuraminidase/metabolismo , Segurança do Paciente , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Proteínas Virais/metabolismo
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