Equivalence Study of Specificity of PPD

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:

1. 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 local and
systemic reactogenicity events.

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])