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A Study of the Efficacy and Safety of the LEISH-F2 + MPL-SE Vaccine for Treatment of Cutaneous Leishmaniasis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Infectious Disease Research Institute
ClinicalTrials.gov Identifier:
NCT01011309
First received: November 9, 2009
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Cutaneous Leishmaniasis
Biological: LEISH-F2 + MPL-SE
Drug: Sodium stibogluconate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of the LEISH-F2 + MPL-SE Vaccine in the Treatment of Patients With Cutaneous Leishmaniasis

Resource links provided by NLM:


Further study details as provided by Infectious Disease Research Institute:

Primary Outcome Measures:
  • Date of Clinical Cure [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    Efficacy of immunotherapy with the LEISH-F2 + MPL-SE vaccine was compared to the efficacy of chemotherapy with sodium stibogluconate in the treatment of CL. Efficacy is measured by the date of clinical cure.

  • Adverse Events of Grade 1 Severity or Higher Occurring in ≥ 3 Patients During Active Treatment Phase of the Study. [ Time Frame: Day 0 through Day 84 ] [ Designated as safety issue: Yes ]
    Safety of immunotherapy with the vaccine was compared to the safety of chemotherapy with sodium stibogluconate. All adverse events are listed regardless of relatedness.


Secondary Outcome Measures:
  • IgG Antibodies and T-cell Cytokine Responses (IFN-g and IL-10) [ Time Frame: Days 0, 56 or 84, and 168 ] [ Designated as safety issue: No ]
    Immunogenicity of the vaccine was evaluated by measuring IgG antibody and T-cell responses to the LEISH-F2 protein and soluble Leishmania antigen (SLA). IgG antibodies were measured by ELISA and T-cell cytokine responses (IFN-g and IL-10) were measured by Luminex. Data is presented as median Post:Pre ratios comparing Days 56/84 or 168 to baseline at Day 0.


Enrollment: 45
Study Start Date: October 2009
Study Completion Date: December 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEISH-F2 + MPL-SE vaccine
Recombinant three antigen Leishmania polyprotein + MPL-SE adjuvant
Biological: LEISH-F2 + MPL-SE
10 μg LEISH-F2 + 25 μg MPL-SE on Days 0, 28 and 56
Other Name: There are no other names for the vaccine.
Active Comparator: Sodium stibogluconate (SSG)
20 mg/kg/day IV for 20 days
Drug: Sodium stibogluconate
20 mg/kg/day IV daily for 20 days
Other Name: Marfan SSG

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011309

Locations
Peru
Instituto de Medicina Tropical"Alexander von Humboldt"
Lima, Peru
Sponsors and Collaborators
Infectious Disease Research Institute
Investigators
Study Director: Franco Piazza, MD, MPH Infectious Disease Research Institute
  More Information

No publications provided

Responsible Party: Infectious Disease Research Institute
ClinicalTrials.gov Identifier: NCT01011309     History of Changes
Other Study ID Numbers: IDRI-LCVTC-202
Study First Received: November 9, 2009
Results First Received: September 16, 2013
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Infectious Disease Research Institute:
Leishmaniasis
vaccine
immunotherapy

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Parasitic Diseases
Protozoan Infections
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Parasitic
Antimony Sodium Gluconate
Anthelmintics
Anti-Infective Agents
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Pharmacologic Actions
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014