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Malar J. 2017 May 4;16(1):188. doi: 10.1186/s12936-017-1832-x.

Safety and efficacy of the choline analogue SAR97276 for malaria treatment: results of two phase 2, open-label, multicenter trials in African patients.

Author information

1
Institut für Tropenmedizin, Universitätsklinikum Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany. janaheld@hotmail.de.
2
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. janaheld@hotmail.de.
3
German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany. janaheld@hotmail.de.
4
Institut für Tropenmedizin, Universitätsklinikum Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany.
5
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
6
Centre Muraz-IRSS, Bobo-Dioulasso, Burkina Faso.
7
Centre de Recherche Entomologique de Cotonou, Cotonou, Benin.
8
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.
9
Ifakara Health Research Center, Bagamoyo, United Republic of Tanzania.
10
Sanofi Research and Development, Chilly-Mazarin, France.
11
Département de Parasitologie, Mycologie, Médecine Tropicale, Université des Sciences de la Santé, Libreville, Gabon.
12
KEMRI Walter Reed Project, Kisumu, Kenya.
13
German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany.
14
Groupe de Recherche Action en Santé, Ouagadougou, Burkina Faso.
15
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
16
Institut für Tropenmedizin, Universitätsklinikum Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany. peter.kremsner@uni-tuebingen.de.
17
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. peter.kremsner@uni-tuebingen.de.
18
German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany. peter.kremsner@uni-tuebingen.de.

Abstract

BACKGROUND:

Malaria remains one of the most important infectious diseases. Treatment options for severe malaria are limited and the choline analogue SAR97276A is a novel chemical entity that was developed primarily as treatment for severe malaria. Before starting clinical investigations in severely ill malaria patients, safety and efficacy of SAR97276A was studied in patients with uncomplicated malaria. Here, we summarize two open-label, multi-center phase 2 trials assessing safety and efficacy of parenterally administered SAR97276A in African adults and children with falciparum malaria.

RESULTS:

Study 1 was conducted in Burkina Faso, Gabon, Benin and Tanzania between August 2008 and July 2009 in malaria patients in an age de-escalating design (adults, children). A total of 113 malaria patients received SAR97276A. Adults were randomized to receive a single dose SAR97296A given either intramuscularly (IM) (0.18 mg/kg) or intravenously (IV) (0.14 mg/kg). If a single dose was not efficacious a second adult group was planned to test a three dose regimen administered IM once daily for 3 days. Single dose SAR97276A showed insufficient efficacy in adults (IM: 20 of 34 cured, 59%; and IV: 23/30 cured, 77%). The 3-day IM regimen showed acceptable efficacy in adults (27/30, 90%) but not in children (13/19, 68%). SAR97276A was well tolerated but no further groups were recruited due lack of efficacy. Study 2 was conducted between October 2011 and January 2012 in Burkina Faso, Gabon and Kenya. SAR97276A administered at a higher dose given IM was compared to artemether-lumefantrine. The study population was restricted to underage malaria patients to be subsequently enrolled in two age cohorts (teenagers, children). Rescue therapy was required in all teenaged malaria patients (8/8) receiving SAR97276A once daily (0.5 mg/kg) for 3 days and in 5 out of 8 teenaged patients treated twice daily (0.25 mg/kg) for 3 days. All patients (4/4) in the control group were cured. The study was stopped, before enrollment of children, due to lack of efficacy but the overall safety profile was good.

CONCLUSIONS:

Monotherapy with SAR97276A up to twice daily for 3 days is not an efficacious treatment for falciparum malaria. SAR97276A will not be further developed for the treatment of malaria. Trial registration at clinicaltrials.gov: NCT00739206, retrospectively registered August 20, 2008 for Study 1 and NCT01445938 registered September 26, 2011 for Study 2.

KEYWORDS:

Africa; Choline analogue; Malaria; P. falciparum; Phase 2; SAR97276A

PMID:
28472957
PMCID:
PMC5418711
DOI:
10.1186/s12936-017-1832-x
[Indexed for MEDLINE]
Free PMC Article

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