Trial reportThe Journal of infectious diseases2018
A Randomized Trial Evaluating the Prophylactic Activity of DSM265 Against Preerythrocytic Plasmodium falciparum Infection During Controlled Human Malarial Infection by Mosquito Bites and Direct Venous Inoculation.
Trial report in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Pooled it
- Reproducibility of malaria sporozoite challenge model in humans for evaluating efficacy of vaccines and drugs: a systematic review.BMC infectious diseases · 2021Pooled it
- Trial
- Safety, Pharmacokinetics, and Causal Prophylactic Efficacy of KAF156 in a Plasmodium falciparum Human Infection Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study.The Lancet. Infectious diseases · 2018Trial
- Topliss-Guided Optimization of Acetanilide-Based Soluble Epoxide Hydrolase Inhibitors: Exploring the Pentafluorosulfanyl Group as a Potency-Enhancing Motif.ChemMedChem · 2026Article
- Malaria Prevention: Progress to Date.Drugs · 2026Review
- ReLink-PyB: an adapted REINVENT-based framework for non-DSM PfDHODH inhibitor discovery.Scientific reports · 2026Article
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
- Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.Journal of medicinal chemistry · 2025Article
- Statistical design and analysis of controlled human malaria infection trials.Malaria journal · 2024Article
- Recent advances, challenges and updates on the development of therapeutics for malaria.EXCLI journal · 2024Review
- Article
- Article
- A pharmacokinetic-pharmacodynamic model for chemoprotective agents against malaria.CPT: pharmacometrics & systems pharmacology · 2023Article
- Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs.The American journal of tropical medicine and hygiene · 2022Article
- Development of a biomarker to monitor target engagement after treatment with dihydroorotate dehydrogenase inhibitors.Biochemical pharmacology · 2022Article
- Siccanin Is a Dual-Target Inhibitor ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series.Journal of medicinal chemistry · 2021Article
Corrections and comments
- Erratum issuedErratum.2018
Authors and funding
25 authors at 6 institutions in 2 countries.
Funding
Abstract
Background: DSM265 is a selective inhibitor of Plasmodium dihydroorotate dehydrogenase that fully protected against controlled human malarial infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites when administered 1 day before challenge and provided partial protection when administered 7 days before challenge. Methods: A double-blinded, randomized, placebo-controlled trial was performed to assess safety, tolerability, pharmacokinetics, and efficacy of 1 oral dose of 400 mg of DSM265 before CHMI. Three cohorts were studied, with DSM265 administered 3 or 7 days before direct venous inoculation of sporozoites or 7 days before 5 bites from infected mosquitoes. Results: DSM265-related adverse events consisted of mild-to-moderate headache and gastrointestinal symptoms. DSM265 concentrations were consistent with pharmacokinetic models (mean area under the curve extrapolated to infinity, 1707 µg*h/mL). Placebo-treated participants became positive by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and were treated 7-10 days after CHMI. Among DSM265-treated subjects, 2 of 6 in each cohort were sterilely protected. DSM265-treated recipients had longer times to development of parasitemia than placebo-treated participants (P < .004). Conclusions: This was the first CHMI study of a novel antimalarial compound to compare direct venous inoculation of sporozoites and mosquito bites. Times to qRT-PCR positivity and treatment were comparable for both routes. DSM265 given 3 or 7 days before CHMI was safe and well tolerated but sterilely protected only one third of participants.
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What OpenQuestion holds
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.