6 research outputs found
Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group
No full textBackground. Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4–5 years, 6–11 years, or 12–16 years). Methods. Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers [GMTs]); and safety were evaluated per age group through ∼4 years postvaccination. Results. VE against VCD across serotypes was 43.5% (95% confidence interval [CI]: 25.3%, 57.3%) for 4–5 year-olds; 63.5% (95% CI: 56.9%, 69.1%) for 6–11 year-olds, and 67.7% (95% CI: 57.8%, 75.2%) for 12–16 year-olds. VE against hospitalized VCD was 63.8% (95% CI: 21.1%, 83.4%), 85.1% (95% CI: 77.1%, 90.3%), and 89.7% (95% CI: 77.9%, 95.2%), for the 3 age groups, respectively. GMTs remained elevated against all 4 serotypes for ∼4 years postvaccination, with no evident differences across age groups. No clear differences in safety by age were identified. Conclusions. This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4–16 years of age living in dengue endemic areas. Relatively lower VE in 4–5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group
Three-year Efficacy and Safety of Takeda’s Dengue Vaccine Candidate (TAK-003)
No full textBACKGROUND: Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. METHODS: Healthy 4–16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. RESULTS: Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6–66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8–88.4) against hospitalized VCD. Efficacy was 54.3% (41.9–64.1) against VCD and 77.1% (58.6–87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9–70.1) against VCD and 86.0% (78.4–91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5–54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6–83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned
Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination
No full textBackground: We explored the impact of prior yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda\u27s dengue vaccine candidate, TAK-003. Methods: Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific reverse-transcription polymerase chain reaction. YF and JE vaccination history was recorded. Results: Of the 20 071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy (95% confidence interval) was 55.7% (39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups. Conclusions: The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings. Clinical Trials Registration. NCT02747927
Efficacy of a Dengue Vaccine Candidate (TAK-003) in Healthy Children and Adolescents 2 Years after Vaccination
No full textBACKGROUND: Takeda\u27s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. METHODS: Children (20 099, 4-16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. RESULTS: Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%-77.3%), including 67.0% (95% CI, 53.6%-76.5%) in dengue-naive and 89.2% (95% CI, 82.4%-93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%-66.8%) with the largest decline in 4-5 year olds (24.5%; 95% CI, -34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%-72.4%) in 6-11 year and 71.2% (95% CI, 41.0%-85.9%) in 12-16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. CONCLUSIONS: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further.Clinical Trials Registration. NCT02747927.Takeda\u27s tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4-16 year olds in dengue-endemic countries
Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial
No full textBackground: About half of the world\u27s population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents. Methods: In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4–16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927. Findings: Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0–65·8) against virologically confirmed dengue and 84·1% (77·8–88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6–62·9) and 79·3% (63·5–88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22–57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related. Interpretation: TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals. Funding: Takeda Vaccines. Translations: For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section
Desarrollo de los procesos de fabricación por filamentos fundidos, despolimerización y sinterización para la obtención de un metal duro WC-10 Co
No full textilustraciones a color, diagramas, fotografíasEsta investigación explora la aplicación de la tecnología de fabricación de filamentos fundidos (FFF) para la impresión 3D de metales duros WC-10Co, centrándose en el desarrollo de formulaciones de sistemas poliméricos que incorporan polipropileno injertado con anhídrido maleico, elastómeros termoplásticos y aditivos como cera de parafina y ácido esteárico. El estudio ajusta las variables del proceso a través de las fases de impresión, despolimerización térmica y sinterización. Se realizaron experimentos preliminares para estandarizar variables, incluyendo el mantenimiento de un 48% de volumen de polvo en la materia prima desarrollada y utilizando polvos listos para prensar de grado industrial.
Tras experimentar con las variables de impresión, se lograron densidades relativas en verde de hasta el 99.99%. Se obtuvieron conocimientos sobre los efectos de atmósferas de despolimerización, como el vacío y una mezcla de 75% H2 + 25% N2, permitiendo controlar eficazmente el carbono residual de la degradación de las cadenas poliméricas durante la despolimerización térmica mientras controlaban la microestructura de los metales duros sinterizados. Los experimentos demuestran que mediante FFF se puede producir metales duros con niveles de dureza que varían de 1300 HV30 a 1500 HV30 y una tenacidad a la fractura entre 12 y 24 MPa√m, comparable a los métodos convencionales.
Los cambios dimensionales durante la sinterización se analizaron en respuesta al tiempo de sinterización y a la atmósfera de despolimerización, ayudando a predecir las desviaciones angulares, diametrales y longitudinales necesarias para escalar las muestras impresas a sus dimensiones finales, lo cual también mostró una correlación directa con los parámetros del proceso de despolimerización térmica. Los experimentos de corte con herramientas impresas en 3D y prensadas revelaron que no hay diferencias estadísticas en el comportamiento de desgaste, validando la competencia funcional de los metales duros impresos en 3D (Texto tomado de la fuente).This research explores the application of fused filament fabrication (FFF) technology for 3D printing WC-10Co hardmetals, focusing on developing binder formulations that incorporate polypropylene grafted with maleic anhydride, thermoplastic elastomers, and additives like wax and stearic acid. The study adjusts process variables across printing, thermal debinding, and sintering phases. Preliminary experiments were conducted to standardize variables, including maintaining a 48% powder volume in the feedstock and utilizing industrial-grade Ready-to-Press powders.
After experimenting with printing variables, relative green densities up to 99.99 % were achieved. Insights were gained on optimal sintering times and the effects of debinding atmospheres, such as vacuum and a 75% H2 + 25% N2 mixture, which effectively removed residual carbon from polymer chain degradation during thermal debinding while controlling the microstructure of the sintered hardmetals. The experiments demonstrate that FFF can produce hardmetals with hardness levels ranging from 1300 HV30 to 1500 HV30 and fracture toughness between 12 to 24 MPa√m, comparable to conventional methods.
Dimensional changes during sintering were analyzed in response to sintering time and debinding atmosphere, aiding in predicting angular, diametral, and longitudinal deviations necessary to scale printed samples to their final dimensions, which also showed a direct correlation with the thermal debinding processing parameters. Cutting experiments with both 3D printed and conventionally pressed tools revealed no statistical differences in wear behavior, validating the functional competence of 3D printed hardmetals.Technological development for the manufacture of metal tools using additive manufacturing techniques based on extrusion for high temperature and wear applications used by the Colombian auto parts industry” with the code 82305—110189082305 and contingent recovery financing contract number 2021–1012 of 2021 celebrated between the Colombian institute of educational credit and technical studies abroad, “Mariano Ospina Pérez”—ICETEX, the Ministry of Science, Technology and Innovation, and the National University of Colombia• Implementation of additive manufacturing technologies for ceramic materials as a complement to R&D+i processes at Universidad Nacional de Colombia," supported by Hermes code: 57440"Advanced Manufacturing and Society 5.0" research seedbed, with Hermes ID: 3965DoctoradoDoctor en IngenieriaProcesos de Manufactura y Metalurgi
