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Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria

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Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria. / Gansane, Adama; Lingani, Moussa; Yeka, Adoke; Nahum, Alain; Bouyou-Akotet, Marielle; Mombo-Ngoma, Ghyslain; Kaguthi, Grace; Barceló, Catalina; Laurijssens, Bart; Cantalloube, Cathy; Macintyre, Fiona; Djeriou, Elhadj; Jessel, Andreas; Bejuit, Raphaël; Demarest, Helen; Marrast, Anne Claire; Debe, Siaka; Tinto, Halidou; Kibuuka, Afizi; Nahum, Diolinda; Mawili-Mboumba, Denise Patricia; Zoleko-Manego, Rella; Mugenya, Irene; Olewe, Frederick; Duparc, Stephan; Ogutu, Bernhards.

In: MALARIA J, Vol. 22, No. 1, 03.01.2023, p. 2.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gansane, A, Lingani, M, Yeka, A, Nahum, A, Bouyou-Akotet, M, Mombo-Ngoma, G, Kaguthi, G, Barceló, C, Laurijssens, B, Cantalloube, C, Macintyre, F, Djeriou, E, Jessel, A, Bejuit, R, Demarest, H, Marrast, AC, Debe, S, Tinto, H, Kibuuka, A, Nahum, D, Mawili-Mboumba, DP, Zoleko-Manego, R, Mugenya, I, Olewe, F, Duparc, S & Ogutu, B 2023, 'Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria', MALARIA J, vol. 22, no. 1, pp. 2. https://doi.org/10.1186/s12936-022-04420-2

APA

Gansane, A., Lingani, M., Yeka, A., Nahum, A., Bouyou-Akotet, M., Mombo-Ngoma, G., Kaguthi, G., Barceló, C., Laurijssens, B., Cantalloube, C., Macintyre, F., Djeriou, E., Jessel, A., Bejuit, R., Demarest, H., Marrast, A. C., Debe, S., Tinto, H., Kibuuka, A., ... Ogutu, B. (2023). Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria. MALARIA J, 22(1), 2. https://doi.org/10.1186/s12936-022-04420-2

Vancouver

Gansane A, Lingani M, Yeka A, Nahum A, Bouyou-Akotet M, Mombo-Ngoma G et al. Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria. MALARIA J. 2023 Jan 3;22(1):2. https://doi.org/10.1186/s12936-022-04420-2

Bibtex

@article{40d9ca5066e247f3b99f5eafc21aa8a8,
title = "Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria",
abstract = "BACKGROUND: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated.METHODS: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14-69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated.RESULTS: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0-∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0-d28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan-Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline.CONCLUSION: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03660839 (7 September, 2018).",
keywords = "Humans, Antimalarials/pharmacology, Plasmodium falciparum, Malaria, Falciparum/drug therapy, Aminoquinolines/therapeutic use, Treatment Outcome, Drug Combinations",
author = "Adama Gansane and Moussa Lingani and Adoke Yeka and Alain Nahum and Marielle Bouyou-Akotet and Ghyslain Mombo-Ngoma and Grace Kaguthi and Catalina Barcel{\'o} and Bart Laurijssens and Cathy Cantalloube and Fiona Macintyre and Elhadj Djeriou and Andreas Jessel and Rapha{\"e}l Bejuit and Helen Demarest and Marrast, {Anne Claire} and Siaka Debe and Halidou Tinto and Afizi Kibuuka and Diolinda Nahum and Mawili-Mboumba, {Denise Patricia} and Rella Zoleko-Manego and Irene Mugenya and Frederick Olewe and Stephan Duparc and Bernhards Ogutu",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = jan,
day = "3",
doi = "10.1186/s12936-022-04420-2",
language = "English",
volume = "22",
pages = "2",
journal = "MALARIA J",
issn = "1475-2875",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria

AU - Gansane, Adama

AU - Lingani, Moussa

AU - Yeka, Adoke

AU - Nahum, Alain

AU - Bouyou-Akotet, Marielle

AU - Mombo-Ngoma, Ghyslain

AU - Kaguthi, Grace

AU - Barceló, Catalina

AU - Laurijssens, Bart

AU - Cantalloube, Cathy

AU - Macintyre, Fiona

AU - Djeriou, Elhadj

AU - Jessel, Andreas

AU - Bejuit, Raphaël

AU - Demarest, Helen

AU - Marrast, Anne Claire

AU - Debe, Siaka

AU - Tinto, Halidou

AU - Kibuuka, Afizi

AU - Nahum, Diolinda

AU - Mawili-Mboumba, Denise Patricia

AU - Zoleko-Manego, Rella

AU - Mugenya, Irene

AU - Olewe, Frederick

AU - Duparc, Stephan

AU - Ogutu, Bernhards

N1 - © 2023. The Author(s).

PY - 2023/1/3

Y1 - 2023/1/3

N2 - BACKGROUND: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated.METHODS: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14-69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated.RESULTS: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0-∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0-d28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan-Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline.CONCLUSION: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03660839 (7 September, 2018).

AB - BACKGROUND: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated.METHODS: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14-69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated.RESULTS: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0-∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0-d28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan-Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline.CONCLUSION: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03660839 (7 September, 2018).

KW - Humans

KW - Antimalarials/pharmacology

KW - Plasmodium falciparum

KW - Malaria, Falciparum/drug therapy

KW - Aminoquinolines/therapeutic use

KW - Treatment Outcome

KW - Drug Combinations

U2 - 10.1186/s12936-022-04420-2

DO - 10.1186/s12936-022-04420-2

M3 - SCORING: Journal article

C2 - 36597076

VL - 22

SP - 2

JO - MALARIA J

JF - MALARIA J

SN - 1475-2875

IS - 1

ER -