The purpose of this study is to determine the efficacy, safety, and immunogenicity of an investigational vaccine being developed for the treatment of leishmaniasis, including cutaneous leishmaniasis (CL). The vaccine, identified as LEISH-F2 + MPL-SE, consists of a Leishmania protein (LEISH-F2) together with an adjuvant MPL-SE.

A phase 2, randomized, open-label, controlled study to evaluate the efficacy, safety, and immunogenicity of the vaccine administered three times (10 μg LEISH-F2 + 25 μg MPL-SE on Days 0, 28 and 56) in the treatment of adults and adolescents with CL compared to treatment with standard chemotherapy (20 mg/kg/day sodium stibogluconate for 20 days). The proportion cured in each group will be determined using clinical criteria.

Inclusion Criteria:

• Males and females ≥ 12 years and < 70 years of age. In the first stage of the study, only patients aged ≥ 18 years and < 70 years will be enrolled. In the second stage, enrollment will also include adolescent patients aged ≥ 12 - < 18 years.
• Must have a clinical diagnosis of cutaneous leishmaniasis confirmed by positive identification of Leishmania parasite and identification of L. peruviana by PCR.
• Lesions must be clear of any superinfection prior to enrollment.
• Female patients of childbearing age must have a negative serum pregnancy test at screening, a negative urine pregnancy test within 24 hours before the first vaccination or initiation of chemotherapy, must not be breast-feeding, and are required to use adequate contraception through Day 84 of the study. These precautions are necessary due to unknown effects that LEISH-F2 + MPL SE, sodium stibogluconate might have in a fetus or newborn infant.
• The following laboratory blood tests must have values within the normal ranges at screening: sodium, potassium, urea, total bilirubin, ALT, AST, glucose, creatinine, alkaline phosphatase, total WBC count and platelet count. Hemoglobin may exceed the ULN since patients reside in the Andes at very high altitude (up to 20 g/dL)
• The following serology tests must be negative at screening: HIV-1/2, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody. All patients (or their parents) will receive HIV-related counseling prior to testing. Patients with positive HIV test results will be referred for counseling and treatment as appropriate.
• Potential study patients (or their guardians) must give written informed consent, be willing to be housed in Lima for a minimum of 20 days and up to 63 days, able to attend all required follow-up visits, have a permanent address, and be reachable by study site personnel.

Exclusion Criteria:

• Infection with species other than L.peruviana as confirmed by PCR.
• Presence of eleven or more active cutaneous leishmaniasis lesions.
• The diameter of the ulcerated area of any single lesion is >60 mm.
• Presence of lesions with superinfection at time of enrollment.
• History of mucocutaneous leishmaniasis or diagnosis of mucocutaneous leishmaniasis at screening.
• History of previous exposure to Leishmania vaccines.
• Known use of injected or oral corticosteroids within 6 weeks prior to the first vaccination or initiation of chemotherapy.
• Participation in another experimental protocol or receipt of any investigational products within 30 days prior to the first vaccination or initiation of chemotherapy.
• History of autoimmune disease or other causes of immunosuppressive states.
• History or evidence of any acute or chronic illness that, in the opinion of the study clinician, may interfere with the evaluation of the safety or the immunogenicity of the vaccine. (Patients presenting with concomitant illness will be referred for standard clinical care).
• History of use of any medication that, in the opinion of the study clinician, may interfere with the evaluation of the safety or the immunogenicity of the vaccine.
• History of significant psychiatric illness.
• Drug addiction including alcohol abuse.
• Patients with a history of previous anaphylaxis, severe allergic reaction to vaccines or unknown allergens, or allergic reaction to eggs.
• Patients who are unlikely to cooperate with the requirements of the study protocol.
• ECG with evidence of ventricular arrythmias ≥ 4 extra systoles per minute.
• Known allergy or contraindication to chemotherapy (e.g., known reaction to pentavalent antimonials, cardiopathy, myocarditis).

Day 0 through Day 336.

All SAEs are listed regardless of relatedness. Other adverse events listed are considered possibly, probably, or definitely related to study vaccination or chemotherapy.

A total of 150 patients was planned, including age de-escalation to adolescents after the first 60 adults enrolled. Owing to slow recruitment and insufficient evidence of efficacy in the immunotherapy group, enrollment was closed early.