Pilot Study of Apremilast (CC-10004) in the Treatment of Moderate to Severe Lichen Planus

This is a phase 2, single center, non-randomized, open label efficacy and safety study
designed to characterize the response of Apremilast 20 mg oral administered twice daily over
12 weeks in subjects with moderate to severe lichen planus. The hypothesis and ideal primary
end point will be that subjects achieve significant clinical response in cutaneous disease
defined as a 2 or more grade improvement of the physician global assessment (PGA) after 12
weeks of treatment.

Many various therapies have been used to treat LP including topical and oral
corticosteroids, retinoids, cyclosporine, griseofulvin, dapsone and phototherapy, but often
with disappointing response.4 It is an inflammatory condition whose pathogenesis involves
damage to basal keratinocytes by alloreactive T cells through the release proinflammatory
cytokines, such as TNF-α and IFN-γ.1 Significantly elevated levels of such inflammatory
mediators are present in tissue from LP lesions compared to normal controls.5 Based on these
observations, the investigation of Apremilast, due to its ability to inhibit multiple
inflammatory cytokines, for the treatment of moderate to severe LP is warranted.

The primary objective of this study is to evaluate the clinical efficacy of Apremilast in
subjects with moderate to severe lichen planus after 12 weeks of treatment. Other objectives
are to evaluate the safety and tolerability of Apremilast, effects on quality of life, and
efficacy for mucosal disease if present.

Inclusion Criteria:

- Must understand and voluntarily sign an informed consent form

- Must be male or female and aged ≥ 18 years at time of consent

- Must be able to adhere to the study visit schedule and other protocol requirements

- Subjects must have stable cutaneous lichen planus appropriate for systemic therapy
based on the following criteria:

- Rated PGA of ≥ 3 (moderate or severe) AND

- ≥ 20 distinct lesions of lichen planus OR

- Refractory to topical corticosteroid therapy (at least 4 weeks of high potency
corticosteroid without significant improvement) OR

- Severe itching/pain that significantly impairs activities of daily living (i.e.
working, school, sleep, etc.)

- Subjects using topical corticosteroids must be tapered and must undergo a washout
period prior to initiation of the study. The washout period for topical
corticosteroids is 2 weeks.

- Must meet the following laboratory criteria:

- Hemoglobin > 12 g/dL

- White blood cell (WBC) count ≥ 3000 /μL (≥ 3.0 X 109/L) and ≤ 14,000/μL (< 14 X
109/L)

- Platelets ≥ 100,000 /μL (≥ 100 X 109/L)

- Serum creatinine ≤ 1.5 mg/dL (or ≤ 133 μmol/L)

- Total bilirubin ≤ 2.0 mg/dL

- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and
alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x
upper limit of normal (ULN)

- Females of childbearing potential (FCBP) must have a negative urine pregnancy test at
screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the
following adequate forms of contraception while on study medication: oral,
injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine
device; barrier contraceptive with spermicide; or vasectomized partner while on
study. A FCBP must agree to have pregnancy tests every 4 weeks while on study.

- Males (including those who have had a vasectomy) must agree to use barrier
contraception (latex condoms) when engaging in sexual activity with FCBP while on
study medication and for 84 days after taking the last dose of study medication

Exclusion Criteria:

- Inability to provide voluntary consent

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Pregnant or breastfeeding

- Systemic fungal infection

- History of active mycobacterial infection with any species (including Mycobacterium
tuberculosis) within 3 years prior to screening visit. Subjects with Mycobacterium
tuberculosis infection more than 3 years prior to screening visit are allowed if
successful treatment was completed at least 3 years prior to randomization and is
documented and available for verification.

- Latent Mycobacterium tuberculosis infection as indicated by a positive Purified
Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test and
documented completion of treatment for latent TB are eligible. Subjects with a
positive PPD skin test and not treated or no documentation of completion of treatment
are ineligible.

- If QuantiFERON® test is performed instead of the PPD test, only those with a negative
QuantiFERON® test are allowed in the study.

- History of incompletely treated Mycobacterium tuberculosis infection as indicated by

- Subject's medical records documenting incomplete treatment for Mycobacterium
tuberculosis

- Subject's self-reported history of incomplete treatment for Mycobacterium
tuberculosis

- History of recurrent bacterial infection (at least 3 major infections resulting in
hospitalization and/or requiring intravenous antibiotic treatment within the past 2
years)

- Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest
x-rays performed within 3 months prior to start of study drug are acceptable.

- Use of topical cyclosporine, tacrolimus, or pimecrolimus within 2 weeks prior to
start of study drug

- Use of systemic or intralesional corticosteroids, systemic retinoids, antimalarials,
azathioprine, methotrexate, mycophenolate mofetil, dapsone, thalidomide,
sulfasalazine, cyclosporine, metronidazole, griseofulvin, or phototherapy within 4
weeks prior to start of study drug

- Use of etanercept within 8 weeks prior to start of study drug.

- Use of adalimumab or infliximab within 12 weeks prior to start of study drug

- Use of alefacept within 24 weeks prior to start of study drug.

- Use of any investigational medication within 4 weeks prior to start of study drug or
5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer)

- Any clinically significant abnormality on 12-lead ECG at screening

- History of congenital or acquired immunodeficiency (eg, Common Variable
Immunodeficiency [CVID])

- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at
screening

- History of Human Immunodeficiency Virus (HIV) infection

- Antibodies to Hepatitis C at screening

- Positive ANA at screening visit

- Malignancy or history of malignancy (except for treated [ie, cured] basal- cell skin
carcinomas > 3 years prior to screening)

- Presence of any other skin condition which may affect the evaluations of the study
disease.

- Clinical picture suspicious for lichenoid drug eruption.

- Subjects whose lichen planus is predominantly hypertrophic, follicular, atrophic, or
bullous variant.

- Lichen planus involving only mucosa or nails.