Trial reportMalaria journal2021
A randomized, double-blind, phase 2b study to investigate the efficacy, safety, tolerability and pharmacokinetics of a single-dose regimen of ferroquine with artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria.
Trial report in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02497612 (A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Trial
- Metal-Drug Complexes as Long-Release Application for Antimalarial PfFNT-Inhibitors.ChemMedChem · 2026Article
- Non-Classical Binding Mechanisms of Ferrocene-Modified Imatinib and Nilotinib Analogues in BCR-ABL1 Kinase Revealed by Computational Analysis.Molecules (Basel, Switzerland) · 2026Article
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- Article
- Making the most of existing antimalarial medicines: a single dose cure with sulfadoxine-pyrimethamine plus artesunate-pyronaridine.Malaria journal · 2025Review
- Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.Science advances · 2025Article
- Synthesis and SAR Studies of Acyl-Thiourea Platinum(II) Complexes Yield Analogs with Dual-Stage Antiplasmodium Activity.ACS medicinal chemistry letters · 2025Article
- Recent advances, challenges and updates on the development of therapeutics for malaria.EXCLI journal · 2024Review
- Review
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Exploring the Potential of Metal-Based Candidate Drugs as Modulators of the Cytoskeleton.Chembiochem : a European journal of chemical biology · 2023Review
- Real-life effectiveness of anti-malarial treatment regimens: what are we aiming for?Malaria journal · 2023Review
- Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model.Antimicrobial agents and chemotherapy · 2023Article
- Investigations on the Novel Antimalarial Ferroquine in Biomimetic Solutions Using Deep UV Resonance Raman Spectroscopy and Density Functional Theory.Analytical chemistry · 2023Article
- Article
- Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery-An Update.Advances in medicine · 2023Review
- Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues.International journal for parasitology. Drugs and drug resistance · 2022Article
- NewAntimicrobial agents and chemotherapy · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 12 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFor uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children ≤ 5 years) and Asia.
methodsThe study was a randomized, double-blind, single-dose, multi-arm clinical trial in patients aged > 6 months to < 70 years, from six African countries and Vietnam. Patients were followed up for 63 days to assess treatment efficacy, safety and pharmacokinetics. The primary efficacy endpoint was the polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) at Day 28 in the Per-Protocol [PP] Set comprising only African patients ≤ 5 years. The exposure-response relationship for PCR-adjusted ACPR at Day 28 and prevalence of kelch-13 mutations were explored.
resultsA total of 373 patients were treated: 289 African patients ≤ 5 years (77.5%), 64 African patients > 5 years and 20 Asian patients. None of the treatment arms met the target efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine dose. Efficacy rates were low in Vietnamese patients, ranging from 20 to 40%. A clear relationship was found between drug exposure (artefenomel and ferroquine concentrations at Day 7) and efficacy (primary endpoint), with higher concentrations of both drugs resulting in higher efficacy. Six distinct kelch-13 mutations were detected in parasite isolates from 10/272 African patients (with 2 mutations known to be associated with artemisinin resistance) and 18/20 Asian patients (all C580Y mutation). Vomiting within 6 h of initial artefenomel administration was common (24.6%) and associated with lower drug exposures.
conclusionThe efficacy of artefenomel/ferroquine combination was suboptimal in African children aged ≤ 5 years, the population of interest, and vomiting most likely had a negative impact on efficacy. Trial registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612&draw=2&rank=1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.