DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection Dr Mihály Sulyok,

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DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection Dr Mihály Sulyok, MD, Thomas Rückle, PhD, Alexandra Roth, PhD, Raymund E Mürbeth, MD, Stephan Chalon, PhD, Nicola Kerr, BA(Mod), Sonia Schnieper Samec, PhD, Nathalie Gobeau, PhD, Carlos Lamsfus Calle, MSc, Javier Ibáñez, MSc, Zita Sulyok, MD, Jana Held, PhD, Tamirat Gebru, MSc, Patricia Granados, MSc, Sina Brückner, PhD, Christian Nguetse, PhD, Juliana Mengue, MSc, Albert Lalremruata, MSc, B Kim Lee Sim, PhD, Stephen L Hoffman, MD, Jörg J Möhrle, PhD, Prof Peter G Kremsner, MD, Benjamin Mordmüller, MD The Lancet Infectious Diseases Volume 17, Issue 6, Pages 636-644 (June 2017) DOI: 10.1016/S1473-3099(17)30139-1 Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license Terms and Conditions

Figure 1 Study design and main interventions Red curves show the expected DSM265 concentrations. MPC=minimal parasiticidal concentration. The Lancet Infectious Diseases 2017 17, 636-644DOI: (10.1016/S1473-3099(17)30139-1) Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license Terms and Conditions

Figure 2 Trial profile ECG=electrocardiogram. ITT=intention to treat. PP=per protocol. The Lancet Infectious Diseases 2017 17, 636-644DOI: (10.1016/S1473-3099(17)30139-1) Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license Terms and Conditions

Figure 3 Parasitaemia assessed by quantitative PCR Placebo volunteers (blue) and DSM265 volunteers (red). In cohort 1A, all DSM265 volunteers remained negative, in cohort 2 all became positive. M=malaria defined as positive thick blood smear. The Lancet Infectious Diseases 2017 17, 636-644DOI: (10.1016/S1473-3099(17)30139-1) Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license Terms and Conditions

Figure 4 Concentration of DSM265 and DSM450 over time Individual (spaghetti) concentration–time profiles in plasma of DSM265 (A and C) and DSM450 (B and D) following administration of a single dose of 400 mg DSM265 in cohort 1 (A and B) and cohort 2 (C and D). Participants in cohort 2 (C) who developed malaria on days 11 and 13 are shown in red, the participant with malaria on day 24 is shown in blue, and participants with submicroscopic parasitaemia without malaria are shown in purple. The green shading shows the approximate time of the first cycle of asexual parasitaemia. The Lancet Infectious Diseases 2017 17, 636-644DOI: (10.1016/S1473-3099(17)30139-1) Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license Terms and Conditions