Safety, False-Positive Reactions and Sensitizing Properties of Leishmania Tropica Skin Test Antigen

Study Overview
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Brief Summary
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The efficacy of LtSTA as a skin test antigen depends upon the sensitivity and specificity of the product. This study has been designed to measure the skin test responses to 15, 30, or 50µg doses of LtSTA. The measurements of non-specific reactivity due to components of the antigen solution and the product's ability to sensitize lymphocytes of Leishmania naïve persons when administered intradermally. The presence or absence of a local inflammatory response to the first skin test with each of three doses of LtSTA will provide insight on the specificity of the antigen in a naïve population. The local inflammatory response to LtSTA following the first and second repeat skin tests will indicate if the antigen is sensitizing after intradermal administration.

Official Title
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A Blinded, Placebo Controlled Study Evaluating Safety, False-Positive Reactions and Sensitizing Properties of Leishmania Tropica Skin Test Antigen (LtSTA)

Conditions
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Cutaneous Leishmaniasis

Intervention / Treatment
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* Biological: Leishmania tropica Skin Test Antigen (LtSTA)
* Biological: Leishmania tropica Skin Test Antigen Placebo (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female in good health; Age 18 - 60 years; No past history of leishmaniasis or prior participation in a Leishmania study; No prior skin test with a Leishmania antigen; No occupational, residential, or travel exposure to Leishmania; Positive Candin® or Trichophyton skin test (>= 5 mm induration). Exclusion Criteria: History of adult atopic dermatitis, contact dermatitis to multiple agents, unexplained urticaria, or asthma; Active allergic rhinitis or conjunctivitis; History of allergy or reactions to phenol, polysorbate 80, or glycerol; Medications: currently taking (within the last month) antihistamines or recent history of taking (within the last 1 year) corticosteroids, immunosuppressants; Splenectomy; Active medical disease*; *Active Medical Disease: Any active physical or psychiatric condition that may increase the risks associated with participation in the study or interferes with the interpretation of study results. Included chronic medical illnesses are cardiovascular disease, renal insufficiency, chronic respiratory illness, cirrhosis, chronic hepatitis, chronic pancreatitis, chronic diarrhea, malnutrition, malignancy, autoimmune disease, and asthma. Pregnancy or lactating; Immunization within 4 weeks; History of leishmaniasis; Occupational exposure to Leishmania; Prior participation in a Leishmania study; Prior skin test with Leishmania antigen; Travel history to Leishmania endemic areas; Abnormal screening lab results; Keloid scar formation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LtSTA 15 ug<br>Naive volunteers tested with 15 ug injection of LtSTA. Participants were skin tested on visits 3, 6 and 9 of the study. The results of the skin tests were read after 48 hours (+/- 6 hours) on visits 4, 7 and 10. A final evaluation was performed on visit 11, fourteen days after visit 10. | Biological: Leishmania tropica Skin Test Antigen (LtSTA)<br>* Administer 15 ug, 30 ug or 50 ug of LtSTA into DTH positive volunteers. Repeat drug administration 30 days after initial injection and 60 days after initial injection. Read and interpret reaction 48 hours after each injection. Observe subjects for conversion or adverse reaction.<br>Biological: Leishmania tropica Skin Test Antigen Placebo (Placebo)<br>* Administer Placebo concurrently with 15 ug, 30 ug and 50 ug doses of LtSTA. Read and interpret the reaction 48 hours after injection. Observe subjects for reaction to Placebo<br>|
| Active Comparator: LtSTA 30 ug<br>Naive volunteers tested with 30 ug injection of LtSTA.Participants were skin tested on visits 3, 6 and 9 of the study. The results of the skin testes were read after 48 hours (+/- 6 hours) on visits 4, 7 and 10. A final evaluation was performed on visit 11, fourteen days after visit 10. | Biological: Leishmania tropica Skin Test Antigen (LtSTA)<br>* Administer 15 ug, 30 ug or 50 ug of LtSTA into DTH positive volunteers. Repeat drug administration 30 days after initial injection and 60 days after initial injection. Read and interpret reaction 48 hours after each injection. Observe subjects for conversion or adverse reaction.<br>Biological: Leishmania tropica Skin Test Antigen Placebo (Placebo)<br>* Administer Placebo concurrently with 15 ug, 30 ug and 50 ug doses of LtSTA. Read and interpret the reaction 48 hours after injection. Observe subjects for reaction to Placebo<br>|
| Active Comparator: LtSTA 50 ug<br>Naive volunteers tested with 50 ug injection of LtSTA.Participants were skin tested on visits 3, 6 and 9 of the study. The results of the skin testes were read after 48 hours (+/- 6 hours) on visits 4, 7 and 10. A final evaluation was performed on visit 11, fourteen days after visit 10. | Biological: Leishmania tropica Skin Test Antigen (LtSTA)<br>* Administer 15 ug, 30 ug or 50 ug of LtSTA into DTH positive volunteers. Repeat drug administration 30 days after initial injection and 60 days after initial injection. Read and interpret reaction 48 hours after each injection. Observe subjects for conversion or adverse reaction.<br>Biological: Leishmania tropica Skin Test Antigen Placebo (Placebo)<br>* Administer Placebo concurrently with 15 ug, 30 ug and 50 ug doses of LtSTA. Read and interpret the reaction 48 hours after injection. Observe subjects for reaction to Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitizing Effects of LtSTA in Leishmania Naive Adults | Skin test response of subjects in the trial were evaluated 48 hours post injection after each of three skin test given at 30 day intervals in naive individuals (no exposure to the Leishmania organism). (Actual times 0, 30 and 60 days).The outcome measure was designated as number of participants who became sensitized to the Leishmania antigen. This is defined as those participants that had a negative skin test result, followed by a positive response in a subsequent skin test without having been exposed to the Leishmania organism. | 62 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Safety of 15, 30 and 50µg/0.1mL Doses of LtSTA in Healthy Adult Volunteers Who Have Had no Known Previous Exposure to Leishmania Parasites | Local and systemic events following skin test. Local: burning, itching, pain. Systemic: Body aches, dizziness, nausea, weakness. | 74 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leishmaniasis, Delayed-Type Hypersensitivity (DTH), Skin Test, Conversion, Prior exposure to Leishmania major