Equivalence Study of Specificity of PPD

Study Overview
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Brief Summary
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Determine if investigational products and reference standard produce similar responses.

Detailed Description
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Primary: To determine if the 2 investigational products (Aplisol formulated from the new Tuberculin PPD drug substance and the reference standard PPD-S2) produce qualitatively similar responses (positive or negative) in subjects who are uninfected with M. tuberculosis (Mtb) or other mycobacteria. Secondary: To determine if the 2 investigational products have equivalent specificity for detecting subjects currently or previously infected with Mtb; To assess the tolerability of the investigational products in terms of the local and systemic reactogenicity events.

Official Title
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A Randomized, Double-blind, Equivalence Study of the Specificity of Tuberculin Purified Protein Derivative (PPD) (Aplisol®) in Comparison With a Reference Standard

Conditions
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Tuberculosis Infection

Intervention / Treatment
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* Biological: Aplisol@ PPD material
* Biological: Reference Standard


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or nonpregnant females, age 18 to 70 years Negligible risk of manifesting a positive PPD test as evidenced by: Prior history of negative PPD test or interferon gamma release assay (IGRA) within 14 months before Screening No history of Bacillus Calmette- Guérin vaccination; or if vaccination status is uncertain, was born in the US and did not live outside the US as a child No history of Mtb or Mtb therapy (including isoniazid, rifampin, ethambutol, pyrazinamide, or streptomycin) No history of infection with atypical mycobacteria, including suspicious chest roentgenogram No history of high risk medical conditions (eg, HIV infection or other immunosuppressive conditions, severe chronic renal disease [as evidenced by a creatinine clearance < 30 ml/min], poorly controlled diabetes mellitus, silicosis, intravenous drug use, or alcohol abuse) No known close contact to a confirmed Mtb case (family or social setting) No history of living or travelling in India, China, Sub-Saharan Africa, or Southeast Asia in the past 6 months No exposure (other than casual) to high-risk environments for Mtb exposure (eg, prisons, homeless shelters); healthcare workers are allowed Exclusion Criteria: Subject is of childbearing potential and unable to use contraceptives; is planning pregnancy; is pregnant or lactating History of anaphylactic type reaction or other severe reaction to PPD in the past, including a history of blistering or sloughing Presence of conditions that may suppress TST reactivity, including: Protocol No. JHP-Aplisol-03 Confidential 04 May 2012 Page 8 of 38 Acute viral infections, including measles, mumps, chicken pox, human immunodeficiency virus (HIV1, HIV2). Mild viral syndromes are allowed. Acute bacterial infections including typhoid fever, brucellosis, typhus, leprosy, or pertussis Acute systemic fungal infection Live virus vaccinations within the past 6 weeks, including measles, mumps, polio, varicella, or FluMist® Metabolic derangements (eg, poorly controlled diabetes, Cushing syndrome, chronic renal failure [as evidenced by a creatinine clearance < 30 ml/min])

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aplisol<br>To confirm the response of PPD materials | Biological: Aplisol@ PPD material<br>* Determine equivalency of materials<br>* Other names: Aplisol@;Biological: Reference Standard<br>* Reference standard material for comparison to newly produced materials.<br>* Other names: US Reference Standard;|
| Active Comparator: PPD Standard<br>Determine equivalent specificity for new material compared to standard material. | Biological: Aplisol@ PPD material<br>* Determine equivalency of materials<br>* Other names: Aplisol@;Biological: Reference Standard<br>* Reference standard material for comparison to newly produced materials.<br>* Other names: US Reference Standard;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of similarity in responses | To determine if the 2 investigational products (Aplisol formulated from the new Tuberculin PPD drug substance and the reference standard PPD-S2) produce qualitatively similar responses (positive or negative) in subjects who are uninfected with M. tuberculosis (Mtb) or other mycobacteria.Skin test responses will be used to determine product similarity in responses. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine equivalent specificity | To determine if the 2 investigational products have equivalent specificity for detecting subjects currently or previously infected with Mtb; 2) To assess the tolerability of the investigational products in terms of the localand systemic reactogenicity events. Skin responses to new PPD and reference standard will be monitored to determine equivalent specificity. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TB, Aplisol