New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia
Introduction Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and vari...
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2021-12-01
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| author | Isabela Ribeiro Joaquim Gascon Sergi Sanz Faustino Torrico Dolors Soy Cristina Alonso-Vega Julio A Urbina María-Jesús Pinazo Jimy José Pinto Virginia R Gonzalez Gimena Rojas Lourdes Ortiz Wilson Garcia Daniel Lozano Rosa A Maldonado Rana Nagarkatti Alain Debrabant Alejandro Schijman M Carmen Thomas Manuel Carlos López Katja Michael Igor C Almeida |
| author_facet | Isabela Ribeiro Joaquim Gascon Sergi Sanz Faustino Torrico Dolors Soy Cristina Alonso-Vega Julio A Urbina María-Jesús Pinazo Jimy José Pinto Virginia R Gonzalez Gimena Rojas Lourdes Ortiz Wilson Garcia Daniel Lozano Rosa A Maldonado Rana Nagarkatti Alain Debrabant Alejandro Schijman M Carmen Thomas Manuel Carlos López Katja Michael Igor C Almeida |
| author_sort | Isabela Ribeiro |
| collection | DOAJ |
| description | Introduction Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs.Methods and analysis New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping.Ethics and dissemination The TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions.Trial registration number NCT03981523. |
| format | Article |
| id | doaj-art-88aac49b17434c19a479ab94608f5d2b |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-12-01 |
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| series | BMJ Open |
| spelling | doaj-art-88aac49b17434c19a479ab94608f5d2b2025-08-20T02:48:53ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-052897New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of BoliviaIsabela Ribeiro0Joaquim Gascon1Sergi Sanz2Faustino Torrico3Dolors Soy4Cristina Alonso-Vega5Julio A Urbina6María-Jesús Pinazo7Jimy José Pinto8Virginia R Gonzalez9Gimena Rojas10Lourdes Ortiz11Wilson Garcia12Daniel Lozano13Rosa A Maldonado14Rana Nagarkatti15Alain Debrabant16Alejandro Schijman17M Carmen Thomas18Manuel Carlos López19Katja Michael20Igor C Almeida2120 Dynamic Portfolio Unit, Drugs for Neglected Diseases initiative, Geneva, Switzerland1 Barcelona Institute for Global Health (ISGLOBAL), Barcelona, SpainMaternal, Child and Reproductive Health Initiative, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic- Universitat de Barcelona, Barcelona, Spain7 Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of13 Pharmacy Service, Division of Medicines, Hospital Clinic de Barcelona, Barcelona, Spain1 Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain2 Center for Biochemistry and Biophysics, Venezuelan Institute for Scientific Research (IVIC), Caracas, Distrito Capital, Venezuela, Bolivarian Republic of1 Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain7 Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of8 Department of Biological Sciences, The University of Texas at El Paso, El Paso, Texas, USA7 Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of9 Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Tarija, Bolivia, Plurinational State of11 Centro Plataforma Chagas Sucre, Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Sucre, Bolivia, Plurinational State of7 Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of8 Department of Biological Sciences, The University of Texas at El Paso, El Paso, Texas, USA15 Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA15 Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA16 Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Buenos Aires, Argentina18 Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina López-Neyra, Granada, Spain18 Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina López-Neyra, Granada, Spain19 Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, Texas, USA8 Department of Biological Sciences, The University of Texas at El Paso, El Paso, Texas, USAIntroduction Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs.Methods and analysis New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping.Ethics and dissemination The TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions.Trial registration number NCT03981523.https://bmjopen.bmj.com/content/11/12/e052897.full |
| spellingShingle | Isabela Ribeiro Joaquim Gascon Sergi Sanz Faustino Torrico Dolors Soy Cristina Alonso-Vega Julio A Urbina María-Jesús Pinazo Jimy José Pinto Virginia R Gonzalez Gimena Rojas Lourdes Ortiz Wilson Garcia Daniel Lozano Rosa A Maldonado Rana Nagarkatti Alain Debrabant Alejandro Schijman M Carmen Thomas Manuel Carlos López Katja Michael Igor C Almeida New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia BMJ Open |
| title | New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia |
| title_full | New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia |
| title_fullStr | New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia |
| title_full_unstemmed | New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia |
| title_short | New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia |
| title_sort | new chemotherapy regimens and biomarkers for chagas disease the rationale and design of the teseo study an open label randomised prospective phase 2 clinical trial in the plurinational state of bolivia |
| url | https://bmjopen.bmj.com/content/11/12/e052897.full |
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