Apremilast in the Treatment of Moderate to Severe Acne
Condition: Acne
MeSH terms: Acne Vulgaris
Intervention: apremilast
Intervention description: apremilast 20 mgs orally twice a day for 12 weeks
Intervention MeSH terms: Apremilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: acne

Summary:

      Acne is a chronic inflammatory disease of the pilosebaceous unit that affects 80-90% of the
      population, especially teenagers, although adult acne is a significant problem for 3-6 % of
      adult men and 5-12% of adult women. Although acne is not a life-threatening disease, it
      produces significant psychological disturbances and permanent skin scars.

      A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the
      treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of
      tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are
      elevated in inflammatory acne.

      Our intention is to study Apremilast in the treatment of moderate to severe acne.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must understand and voluntarily sign an informed consent form.

          -  Must be male or female and aged 18-45 years of age, inclusive, at time of consent and
             be in general good health.

          -  Must be able to adhere to the study visit schedule and other protocol requirements

          -  Moderate to severe acne ( a 3 or 4 score in the RGA) of the face at Baseline.

          -  Subjects with 17-100 non-inflammatory lesions (open and closed comedones) and with
             25-150 inflammatory lesions (papules and pustules) and 0-15 nodules (no larger than 1
             cm each) and no cystic lesions.

          -  Must meet the following laboratory criteria:

               -  Hemoglobin > 12 g/dL

               -  White blood cell (WBC) count ≥ 3000 /mL (≥ 3.0 X 109/L) and ≤ 14,000/mL (< 14 X
                  109/L)

               -  Platelets ≥ 100,000 /mL (≥ 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)

                    -  Negative ANA

                    -  Negative cANCA

                    -  Negative antiphospholipid antibodies

          -  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 medication.

          -  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

          -  If a moisturizer or sunscreen is needed during the study, subjects must be willing to
             accept only acceptable products (non-comedogenic and without ingredients that may
             worsen or improve acne such as Cetaphil cleanser and Neutrogena oil-free moisturizer).

        Exclusion Criteria:

          -  Inability to provide voluntary consent

          -  Use of any topical acne treatment (salicylic acid, benzoyl peroxide, retinol,
             antibiotics) 2 weeks prior to Baseline.

          -  Use of topical astringents or antimicrobial soaps for one week prior to Baseline.

          -  Use of any topical retinoid, systemic antibiotic or topical or systemic
             corticosteroids in the face 4 weeks prior to Baseline.

          -  Use of a systemic retinoid, such as isotretinoin, 6 months prior to Baseline

          -  Any confluent nodule, cyst and/or sinus tract present.

          -  Any nodule larger than 10 mm.

          -  Subjects who are using medications that can exacerbate acne such as mega-doses of
             vitamin D, vitamin B2, B6, B12, haloperidol, halogens such as iodide and bromide,
             lithium, hydantoin and Phenobarbital). Multivitamins, iron supplements and folate are
             acceptable, but should be used consistently throughout the study.

          -  Subjects who have had a facial procedure (chemical or laser peel, blue light
             treatment, microdermabrasion, etc) within 4 weeks before enrollment or during the
             study.

          -  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

          -  Subjects who abuse drugs or alcohol (drug screening not required).

          -  Pregnant, trying to become pregnant or breastfeeding.

          -  Use of estrogens, androgens or hormonal contraception or devices for less than 12
             weeks prior to Baseline. Subjects are allowed to enroll as long as they do not expect
             to change dose, product, or discontinue use during the study.

          -  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.

          -  Mycobacterium tuberculosis infection as indicated by a positive Purified Protein
             Derivative [PPD] skin test (>15mm induration). Subjects with a positive PPD skin test
             are ineligible.

          -  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 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

          -  Malignancy or history of malignancy (except for treated [ie, cured] basal-cell skin
             carcinomas > 3 years prior to screening )