WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study.

Afif Ben Salah (1) , Pierre A Buffet (2) , Gloria Morizot (2) , Nathalie Ben Massoud (1) , Amor Zâatour (1) , Nissaf Ben Alaya (1) , Nabil Bel Haj Hamida (1) , Zaher El Ahmadi (3) , Matthew T Downs (4) , Philip L Smith (5) , Koussay Dellagi (1) , Max Grögl (6)

1 Institut Pasteur de Tunis
2 IP - Institut Pasteur [Paris]
3 Direction Régionale de la Santé de Sidi Bouzid
4 Statistics Collaborative
5 U.S. Army Medical Materiel Development Activity
6 Walter Reed Army Institute of Research

BACKGROUND: Cutaneous leishmaniasis (cl) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France. METHODS: A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180. RESULTS: Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity. CONCLUSION: Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703924.

Domains: Life Sciences [q-bio]

Afif Ben Salah, Pierre A Buffet, Gloria Morizot, Nathalie Ben Massoud, Amor Zâatour, et al.. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study.. PLoS Neglected Tropical Diseases, 2009, 3 (5), pp.e432. ⟨10.1371/journal.pntd.0000432⟩. ⟨pasteur-00859427⟩