Publications

" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research."
Prof Halidou TINTO, PharmD, Msc, PhD Head of the CRUN

2023
Journal Articles
	Bernhards Ogutu, Adoke Yeka, Sylvia Kusemererwa, Ricardo Thompson, Halidou Tinto, Andre Offianan Toure, Chirapong Uthaisin, Amar Verma, Afizi Kibuuka, Moussa Lingani, Carlos Lourenço, Ghyslain Mombo-Ngoma, Videlis Nduba, Tiacoh Landry N'Guessan, Guétawendé Job Wilfried Nassa, Mary Nyantaro, Lucas Otieno Tina, Piyoosh K. Singh, Myriam El Gaaloul, Anne Claire Marrast, Havana Chikoto, Katalin Csermak, Ivan Demin, Dheeraj Mehta, Rashidkhan Pathan, Celine Risterucci, Guoqin Su, Cornelis Winnips, Grace Kaguthi, Bakary Fofana, Martin Peter Grobusch Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial Journal Article In: The Lancet. Infectious diseases, vol. 23, iss. 9, pp. 1051-1061, 2023, ISSN: 1474-4457. Abstract \| BibTeX \| Tags: Adoke Yeka, Adolescent, Adult, Antimalarials, Artemether / pharmacology, Artemether / therapeutic use, Artemisinins, Bernhards Ogutu, Child, Clinical Trial, doi:10.1016/S1473-3099(23)00209-8, Drug Combinations, Ethanolamines / pharmacology, Ethanolamines / therapeutic use, Falciparum* / drug therapy, Falciparum* / parasitology, Fluorenes / pharmacology, Fluorenes / therapeutic use, Humans, Lumefantrine / pharmacology, Lumefantrine / therapeutic use, Malaria, Malaria* / drug therapy, Martin Peter Grobusch, MEDLINE, Multicenter Study, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase II, Plasmodium falciparum, pmid:37327809, PubMed Abstract, Randomized controlled trial, Research Support, Treatment Outcome \| Links: Close Close @article{Ogutu2023, title = {Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial}, author = {Bernhards Ogutu and Adoke Yeka and Sylvia Kusemererwa and Ricardo Thompson and Halidou Tinto and Andre Offianan Toure and Chirapong Uthaisin and Amar Verma and Afizi Kibuuka and Moussa Lingani and Carlos Louren\c{c}o and Ghyslain Mombo-Ngoma and Videlis Nduba and Tiacoh Landry N'Guessan and Gu\'{e}tawend\'{e} Job Wilfried Nassa and Mary Nyantaro and Lucas Otieno Tina and Piyoosh K. Singh and Myriam El Gaaloul and Anne Claire Marrast and Havana Chikoto and Katalin Csermak and Ivan Demin and Dheeraj Mehta and Rashidkhan Pathan and Celine Risterucci and Guoqin Su and Cornelis Winnips and Grace Kaguthi and Bakary Fofana and Martin Peter Grobusch}, url = {https://pubmed.ncbi.nlm.nih.gov/37327809/}, doi = {10.1016/S1473-3099(23)00209-8}, issn = {1474-4457}, year = {2023}, date = {2023-01-01}, journal = {The Lancet. Infectious diseases}, volume = {23}, issue = {9}, pages = {1051-1061}, publisher = {Lancet Infect Dis}, abstract = {Background: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria. Methods: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (\>1000 and \<150 000 parasites per μL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and \<12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to \<6 years and 6 to \<12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020\textendash003284\textendash25) and ClinicalTrials.gov (NCT03167242). Findings: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81\textendash98] with 1 day, 47 of 48 [98%, 89\textendash100] with 2 days, and 42 of 43 [98%, 88\textendash100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83\textendash99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93\textendash100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92\textendash100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86\textendash100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83\textendash99] vs 21 of 22 [96%, 77\textendash100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study. Interpretation: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633). Funding: Novartis and Medicines for Malaria Venture.}, keywords = {Adoke Yeka, Adolescent, Adult, Antimalarials, Artemether / pharmacology, Artemether / therapeutic use, Artemisinins, Bernhards Ogutu, Child, Clinical Trial, doi:10.1016/S1473-3099(23)00209-8, Drug Combinations, Ethanolamines / pharmacology, Ethanolamines / therapeutic use, Falciparum* / drug therapy, Falciparum* / parasitology, Fluorenes / pharmacology, Fluorenes / therapeutic use, Humans, Lumefantrine / pharmacology, Lumefantrine / therapeutic use, Malaria, Malaria* / drug therapy, Martin Peter Grobusch, MEDLINE, Multicenter Study, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase II, Plasmodium falciparum, pmid:37327809, PubMed Abstract, Randomized controlled trial, Research Support, Treatment Outcome}, pubstate = {published}, tppubtype = {article} } Close Background: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria. Methods: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (>1000 and <150 000 parasites per μL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and <12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to <6 years and 6 to <12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020–003284–25) and ClinicalTrials.gov (NCT03167242). Findings: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81–98] with 1 day, 47 of 48 [98%, 89–100] with 2 days, and 42 of 43 [98%, 88–100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83–99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93–100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92–100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86–100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83–99] vs 21 of 22 [96%, 77–100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study. Interpretation: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633). Funding: Novartis and Medicines for Malaria Venture. Close
	Moussa Djimde, Japhet Kabalu Tshiongo, Hypolite Mavoko Muhindo, Halidou Tinto, Esperanca Sevene, Maminata Traore, Anifa Vala, Salesio MacUacua, Berenger Kabore, Edgard Diniba Dabira, Annette Erhart, Hamadoun Diakite, Mohamed Keita, Mireia Piqueras, Raquel González, Clara Menendez, Thomas P. C. Dorlo, Issaka Sagara, Petra Mens, Henk Schallig, Umberto D'Alessandro, Kassoum Kayentao Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial Journal Article In: BMJ open, vol. 13, iss. 10, 2023, ISSN: 2044-6055. Abstract \| BibTeX \| Tags: Antimalarials* / adverse effects, Artemether, Artemether / therapeutic use, Artemisinins* / adverse effects, Clinical Trial Protocol, Clinical Trials, doi:10.1136/bmjopen-2022-065295, Drug Combinations, Falciparum* / drug therapy, Female, Humans, Infant, Japhet Kabalu Tshiongo, Kassoum Kayentao, Lumefantrine Drug Combination / therapeutic use, Malaria, Malaria* / drug therapy, MEDLINE, Moussa Djimde, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III as Topic, PMC10565244, pmid:37813539, Pregnancy, Pregnant Women, PubMed Abstract, Randomized Controlled Trials as Topic, Research Support, Sub-Saharan African People, Treatment Outcome \| Links: Close Close @article{Djimde2023, title = {Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial}, author = {Moussa Djimde and Japhet Kabalu Tshiongo and Hypolite Mavoko Muhindo and Halidou Tinto and Esperanca Sevene and Maminata Traore and Anifa Vala and Salesio MacUacua and Berenger Kabore and Edgard Diniba Dabira and Annette Erhart and Hamadoun Diakite and Mohamed Keita and Mireia Piqueras and Raquel Gonz\'{a}lez and Clara Menendez and Thomas P. C. Dorlo and Issaka Sagara and Petra Mens and Henk Schallig and Umberto D'Alessandro and Kassoum Kayentao}, url = {https://pubmed.ncbi.nlm.nih.gov/37813539/}, doi = {10.1136/BMJOPEN-2022-065295}, issn = {2044-6055}, year = {2023}, date = {2023-01-01}, journal = {BMJ open}, volume = {13}, issue = {10}, publisher = {BMJ Open}, abstract = {Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. Trial registration number PACTR202011812241529.}, keywords = {Antimalarials* / adverse effects, Artemether, Artemether / therapeutic use, Artemisinins* / adverse effects, Clinical Trial Protocol, Clinical Trials, doi:10.1136/bmjopen-2022-065295, Drug Combinations, Falciparum* / drug therapy, Female, Humans, Infant, Japhet Kabalu Tshiongo, Kassoum Kayentao, Lumefantrine Drug Combination / therapeutic use, Malaria, Malaria* / drug therapy, MEDLINE, Moussa Djimde, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III as Topic, PMC10565244, pmid:37813539, Pregnancy, Pregnant Women, PubMed Abstract, Randomized Controlled Trials as Topic, Research Support, Sub-Saharan African People, Treatment Outcome}, pubstate = {published}, tppubtype = {article} } Close Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. Trial registration number PACTR202011812241529. Close