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An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne

Phase 2
18 Years
45 Years
Not Enrolling

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Trial Information

An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne

The hypothesized sequence of events in inflammatory acne starts with the formation of a
microcomedone with accumulation of cornified keratinocytes within the follicle. Presence
and/or proliferation of P.acnes induces the production of IL-1 alpha, tumor necrosis factor
(TNF)- alpha, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Inflammation caused by CD4+ T cells causes a T-helper 1 cytokine response mediated by
Toll-like receptors (TLR)-2 and TLR-4 whose expression is increased by P. acnes.
Infiltration by neutrophils appears 72 hrs after, with possible disruption of the
follicular wall and more inflammation. TNF-alpha liberated by keratinocytes stimulates the
activation of pro-matrix metalloproteinase (MMP)-2 activity in the dermis with remodeling by
fibroblasts with the consequence of possible scarring.

The usual treatment for moderate to severe inflammatory acne involves the use of long-term
topical retinoids and antibiotics such as doxycycline or minocycline that had been showed to
decrease the inflammatory response as well as decreasing the population of P. acnes. Since
acne is a long term condition, several years of antibiotics are usually required. Recently,
the problematic of antibiotic overuse has received great attention and concerns. Chronic
antibiotic use has been implicated in increasing the risk of breast cancer and upper
respiratory infections, and there is also a concern for antibiotic resistance. Recent
recommendations by the Global Alliance to Improve Outcomes in Acne Group include the
limitation for the use of oral antibiotics to a maximum of 3 months. So there is a need to
find alternatives that does not include the use of oral antibiotics.

The only effective and available treatment for severe acne is isotretinoin which may have
potential serious side effects. Lately also it has been implicated in the development of
depression and suicidal ideations in the teenager population.

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. Preliminary data of the use of Apremilast in psoriasis
makes us believe that this medication is safe for short-term use in acne patients.

Our intention is to study Apremilast in the treatment of moderate to severe acne.

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

- 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

- 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

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

- 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

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

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

- 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

- 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 )

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of Patients With a Success Rate (Based on the Researcher's Global Assessment (RGA) Sum of Clear (0) or Almost Clear (1))

Outcome Description:

RGA measures the severity of acne. The scale goes from 0-4. 0 will be better and 4 will be worse. Scores can only be whole numbers (0,1,2,3,4)ordinal.

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

Aida Lugo-Somolinos, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Chapel Hill


United States: Food and Drug Administration

Study ID:




Start Date:

February 2010

Completion Date:

October 2010

Related Keywords:

  • Acne
  • acne
  • Acne Vulgaris



University of North CarolinaChapel Hill, North Carolina  27599