The purpose of this study is to determine the safety and efficacy of etanercept (also known
as Enbrel) in the treatment of moderate to severe lichen planus.
This is a double-blind, placebo-controlled pilot study to observe the safety and efficacy of
etanercept in patients with moderate to severe oral or cutaneous lichen planus.
Etanercept has already been approved by the FDA for treatment of other diseases including
psoriasis. This study will evaluate its safety and effectiveness specifically in treating
lichen planus. Several lines of evidence suggest that TNF-alpha plays a role in the
pathogenesis of lichen planus. Because etanercept inhibits tumor necrosis factor, this
represents a potentially effective therapeutic intervention for diseases in which the role
of TNF-alpha is implicated, such as lichen planus.
The study will involve 8 total clinic visits over 6 months. Eligible subjects will be
randomized either to a treatment group or to a placebo group.
The study is designed in three parts:
- Part 1 (Weeks 1-12) During this time you will be assigned to either receive etanercept
or a placebo twice weekly. You will have a fifty percent chance of receiving the study
drug (etanercept). Neither you nor the staff will know what you are receiving during
- Part 2 (Weeks 13-24) During this time all patients who have not achieved complete
clearance will have the opportunity to receive etanercept (the active drug), regardless
of what group you were assigned to during Part 1. Those that were assigned to receive
etanercept in Part 1 will receive a 50% lower dose of drug for the remainder of the
- Part 3 (Weeks 25-32) During this follow-up period you will not be receiving any study
You must have the ability to self-inject the study drug or have a care giver at home who can
administer the subcutaneous injections twice a week. A study staff will instruct you on
proper injection technique at your baseline visit.
Participants will be compensated $25 for every completed scheduled study visit for a total
of $200 after the completion of the trial.
Inclusion Criteria:Adults over 18 years of age with active, clinically stable lichen
planus with a score of 3 or greater on the physician global assessment for cutaneous or
mucosal disease will be included in this trial. Subjects must also be considered
appropriate for systemic treatment.
Detailed inclusion criteria:
1. Subjects must be at least 18 years of age.
2. Must carry a diagnosis of lichen planus as determined by either a skin or mucosal
3. Patients must have a score of 3 or greater (moderate-severe) on the PGA for cutaneous
or mucosal disease
4. Patient must be considered appropriate for systemic therapy based upon fulfilling one
of the following criteria:
1)Inability to maintain weight due to pain with eating, chewing, or swallowing;
2)Dyspareunia or dysuria due to genital lesions; 3)Itch/pain of sufficient severity that
activities of daily living are significantly affected this includes sleeping, cleansing
oneself, performing one's occupation.
5.Must be off systemic lichen planus treatment (e.g. cyclosporine, systemic retinoids,
hydroxychloroquine, chlorquine, quinacrine, azathioprine, methotrexate, mycophenolate
mofetil, dapsone, thalidomide, PUVA, UVB) for 4 weeks prior to starting the study drug.
Prednisone may be continued during the study if it is at a dose of 10mg/day or less and if
at a stable dose for at least 4 weeks prior to starting the study drug.
6.If using topical corticosteroid to the affected areas, the dose and frequency must be
unchanged for 2 weeks prior to beginning the study agent and during the course of the
7.Must be off topical cyclosporine, tacrolimus or pimecrolimus for 2 weeks prior to
starting the study drug and for the entire duration of the study.
8.Must be able and willing to give written informed consent and comply with the
requirements of the study protocol and must authorize release and use of protected health
9.Women of childbearing potential (i.e. does not include those surgically sterile or at
least 5 years postmenopausal) must have a negative pregnancy test at the time of entry
into the study (negative pregnancy test within 7 days before the first dose of study drug)
10.Women of child-bearing potential must be practicing successful contraception for at
least 3 months prior to the study with one of the following methods (OCPs, IUDs,
diaphragm, spouse or sexual partner uses condom or is surgically sterilized, abstinence).
If using a hormonal form of contraception, the patient will be excluded if they have not
used the same form of hormonal contraception for 90 days prior to the start of the
etanercept (e.g. day 0) or are not willing to continue the use of the same form of
hormonal contraception for the duration of the study. Sexual partners of a male
participant shall have no childbearing potential or practice effective contraception
during and for at least 8 weeks following completion of the study.
11.Subject or designee must have the ability to self-inject investigational product or
have a care giver at home who can administer subcutaneous injections (unless the study
requirements are that all doses will be given at the clinic)
12.Screening laboratory results must be within the following parameters:
- Hemaglobin > 10 g/dL
- White blood cells > 3.5 x 109/L
- Neutrophils> 1.5 x 109/L
- Platelets> 100 x 109/L
- Lymphocytes> 0.5 x 109/L
- Serum creatinine< 1.5 mg/dL
- HCV Antibody = Nonreactive
- AST and ALT < 2X Upper Limit of Normal (ULN) Exclusion Criteria:1.Subject is
currently enrolled in another investigational device or drug trial(s), or subject has
received investigational agent(s) within 90 days of baseline visit.
2.Known HIV-positive status, any other immuno-suppressive disease, or inability to
practice safe sex during the length of the study
3.Subject has been diagnosed with a malignancy within the past 5 years except for
successfully treated non-melanoma skin cancer or in-situ cervical carcinoma.
4.Subject has signs or symptoms of a lymphoproliferative disease.
5.Other skin or mucosal disease that might interfere with lichen planus assessments,
including signs of squamous cell carcinoma.
6.Lichen planus variants including hypertrophic, atrophic, follicular (including
lichen planopilaris), and bullous cutaneous forms.
7.Patients with lichen sclerosis et atrophicus (LS&A)
8.Clinical history and lesion distribution suspicious for a lichenoid drug eruption
9.Severe co-morbidities (diabetes mellitus requiring insulin, CHF of any severity,
MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris,
uncontrolled hypertension (systolic blood pressure <80 mm Hg or > 180 mm Hg or
diastolic blood pressure >110 mm Hg), oxygen-dependent severe pulmonary disease,
history of TB or TB exposure or other mycobacterial disease
10.History of TB or positive PPD at screening (PPD more than 5 mm induration at
48-72h at screening, irrespective of BCG vaccination status). Known history of active
hepatitis B or C, or lupus, SLE, history of multiple sclerosis or prior episode of
central nervous system demyelination, transverse myelitis, optic neuritis, epilepsy,
psychiatric condition), or other chronic serious medical illnesses.
11.Subject has a diagnosis of congestive heart failure of any severity
12.Use of a live vaccine 90 days prior to, or during this study.
13.Previous exposure and/or known sensitivity to etanercept or to any of its
14.Concurrent use, or failure of, any TNF-inhibitor
15.Previous exposure to alefacept or efalizumab within 6 weeks of administration of
16.Concurrent sulfasalazine therapy
17.Prior or concurrent cyclophosphamide therapy
18.Active severe infections (see warning and contraindications in etanercept Package
Insert), or prior infection requiring hospitalization or oral/intravenous antibiotics
within 4 weeks before screening visit, or between the screening and baseline visits.
19.Active inflammatory bowel disease or peptic ulcer disease
20.Drug or alcohol abuse within 12 months of screening visit.
21.History of non-compliance with other therapies
22.Pregnant or lactating
21. Documented presence of any of the following: proteinuria >1+ by dipstick
screening, 24 hour protein excretion more than 0.5 g, symptomatic liver disease with
serum albumin < 3 G/DL, PT or PTT > upper range of control values, or chronic liver
disease (e.g. hepatitis B or C)
22. Documented Forced Vital Capacity < 50% of predicted