DSM265 Phase IIa Investigation Treating Plasmodium Falciparum or Vivax

Summary

This will be a Proof-of-concept / Phase IIa, open label study to examine the efficacy of DSM265 in uncomplicated Plasmodium vivax and Plasmodium falciparum blood-stage malaria in adult patients. A minimum of two cohorts (20 patients) and a maximum of 6 cohorts (60 patients, 3 dose levels) will be tested. The starting dose of DSM265 for the first P. vivax and P. falciparum cohorts will be 400 mg. This dose is expected to show complete clearance of parasites by microscopy by Day 7 and a decrease in recrudescence rate assessed at Day 14 (success criteria for dose de-escalation and continuation of the study).

Timeline

Start

2016-01

Primary completion

2016-01

Completion

2016-01

Outcome

Mixed primary results

paper all 11 (100%) in the 400 mg group and eight (80%) of ten in the 250 mg group achieved ACPR on day 14. PMID 29909069 ↗

paper defined as ACPR (P falciparum) or crude cure (P vivax) in at least 80% of patients in the cohort. PMID 29909069 ↗

paper For the patients with P vivax malaria, the primary endpoint was not met. PMID 29909069 ↗

Publications

• Llanos-Cuentas A, Casapia M, Chuquiyauri R, Hinojosa JC, Kerr N, Rosario M, Toovey S, Arch RH, Phillips MA, Rozenberg FD, Bath J, Ng CL, Cowell AN, Winzeler EA, Fidock DA, Baker M, Mohrle JJ, Hooft van Huijsduijnen R, Gobeau N, Araeipour N, Andenmatten N, Ruckle T, Duparc S. 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. Lancet Infect Dis. 2018 Aug;18(8):874-883. doi: 10.1016/S1473-3099(18)30309-8. Epub 2018 Jun 13.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	DSM265	Small molecule	250 mg	Oral
Subject	DSM265	Small molecule	400 mg	Oral
Subject	DSM265	Small molecule	600 mg	Oral
Subject	DSM265	Small molecule	800 mg	Oral

Indications