Chemoprotective Activity of MMV390048 in PfSPZ Challenge Model

Summary

This study follows a First-In-Human dose-escalation study of MMV390048 (5 to 120 mg MMV390048 powder-in-bottle formulation), a formulation bioavailability study to establish suitable tablet formulation, and a two-part dose-escalation (40 to 120 mg of MMV390048) / induced blood stage malaria (ISBM) challenge study with the new tablet formulation. After identification of the predicted efficacious MMV390048 plasma concentrations in the IBSM model, the current study will evaluate the chemoprotective efficacy of MMV390048 in a standardised and validated controlled human malaria infection (CHMI) model using direct venous inoculation (DVI) of aseptic, purified, cryopreserved, vialed P. falciparum sporozoites (PfSPZ Challenge). Three sequential cohorts of healthy men and women of non-childbearing potential (WONCBP) will be administered the investigational medicinal product (IMP, i.e. MMV390048) under different conditions. This may identify preventative regimens, to be further investigated in a Phase II program. In the first two cohorts, protective administration of the IMP will occur 1 and 7 days before DVI of PfSPZ challenge. The timing of IMP administration and dosage in the last cohort will be determined on the basis of emerging data from the preceding cohorts, but will not exceed 28 days prior to the challenge nor 120 mg MMV390048.

Timeline

Start

2018-01

Primary completion

2018-09

Completion

2018-12

Outcome

Outcome not reported

Stopped: “Repositioning of target indication.”

Publications

• Background Sulyok M, Ruckle T, Roth A, Murbeth RE, Chalon S, Kerr N, Samec SS, Gobeau N, Calle CL, Ibanez J, Sulyok Z, Held J, Gebru T, Granados P, Bruckner S, Nguetse C, Mengue J, Lalremruata A, Sim BKL, Hoffman SL, Mohrle JJ, Kremsner PG, Mordmuller B. DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection. Lancet Infect Dis. 2017 Jun;17(6):636-644. doi: 10.1016/S1473-3099(17)30139-1. Epub 2017 Mar 28.
• Background Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, Lohr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Munoz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.
• Background World Health Organization. World Malaria Report 2015. World Health. 2015;243

Drugs

Indications