Clinical trial NCT00111514: Study to Evaluate the Leish-111F + MPL-SE Vaccine in the Treatment of Mucosal Leishmaniasis
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Study to Evaluate Safety, Tolerability, and Immunogenicity of Leish-111f + MPL-SE Vaccine in Combination With Pentavalent Antimony in Treatment of Mucosal Leishmaniasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leishmaniasis, Mucocutaneous
Keywords: Leishmaniasis
Subunit vaccine
therapeutic
T-cell
pentavalent antimony
Lead sponsor: Access to Advanced Health Institute (AAHI)
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2005-05-23
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety of the Leish-111f + MPL-SE vaccine given as three injections every 28 days at each of three dose levels of Leish-111f protein, in combination with standard pentavalent antimony therapy in adult patients with mucosal leishmaniasis.

Detailed description: Mucosal leishmaniasis is a disfiguring and possibly fatal infection. All available medical therapies require weeks of treatment and cause significant toxicity. In Peru, the standard therapy is daily intravenous (IV) pentavalent antimony (20 mg/kg/day) for 28 days. It appears that Leishmania infections can be eliminated by T helper 1 immune responses. These findings argue that a vaccine that augments mucosal leishmaniasis patients' T helper 1 responses will eliminate the infection and disease. This study is a phase 1, randomized, double-blind, placebo controlled, sequential dose-escalating trial to evaluate the safety and immunogenicity of three injections of 5, 10, or 20 μg of Leish-111f protein + 25 μg of MPL-SE adjuvant given at 4 week intervals as an adjunct to standard chemotherapy with pentavalent antimony (20 mg/kg/day for 28 days) in patients with mucosal leishmaniasis.

Eligibility criteria: Inclusion Criteria:

* Patients with mucosal leishmaniasis confirmed by a positive smear, in vitro culture or PCR test

Exclusion Criteria:

* Mucosal leishmaniasis must not involve the vocal cords or cause respiratory distress, and there must be no evidence of other disease.

Primary outcomes:
measure: Occurrence of dose-limiting toxicity
measure: Adverse events
Secondary outcomes:
measure: IgG and T-cell response to Leish-111f vaccine
measure: Leish-111f skin test reactivity
measure: Safety of the vaccine with respect to the clinical course of mucosal leishmaniasis
Other outcomes:
Locations:
city: Cusco
country: Peru
facility: Clínica de Leishmaniasis, Hospital Nacional Sur Este EsSalud
city: Lima
country: Peru
facility: Universidad Peruana Cayetano Heredia
Study officials:
affiliation: Universidad Peruana Cayetano Heredia
name: Alejandro Llanos-Cuentas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Access to Advanced Health Institute (AAHI)
name: Franco M Piazza, MD, MPh
role: STUDY_DIRECTOR
References:
citation: Llanos-Cuentas A, Calderon W, Cruz M, Ashman JA, Alves FP, Coler RN, Bogatzki LY, Bertholet S, Laughlin EM, Kahn SJ, Beckmann AM, Cowgill KD, Reed SG, Piazza FM. A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with sodium stibogluconate for the treatment of mucosal leishmaniasis. Vaccine. 2010 Oct 28;28(46):7427-35. doi: 10.1016/j.vaccine.2010.08.092. Epub 2010 Sep 17.