Apremilast in the Treatment of Moderate to Severe Acne

• Status: Terminated
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Celgene; Celgene Corporation
• Treatments: Apremilast; Thalidomide

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 )