A Study to Evaluate the Safety and Efficacy of Apremilast in the Treatment of Skin Disease in Patients With Dermatomyositis

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and efficacy of an oral medicine (called apremilast) for treating skin involvement in patients with the disease dermatomyositis.

Official Title
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An Open Label Study Evaluating the Safety and Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Dermatomyositis

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: Apremilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must understand and voluntarily sign an informed consent form Must be 18 years at time of signing informed consent form Must be able to adhere to the study visit schedule and other protocol requirements Patients must have a diagnosis of DM based upon the characteristic cutaneous findings proposed by Sontheimer1 and a skin biopsy consistent with DM Subjects must be a candidate for systemic therapy for their DM skin disease: a subject is considered a candidate, if, in the judgment of the investigator, they are not adequately responding to aggressive sun protection along with the use of potent (e.g. class I or II) topical corticosteroids and/or immunomodulators Must have cutaneous disease activity of at least moderate on a 5 point Likert scale (using the PGA) Must have cutaneous disease activity score of at least 5 on the CDASI (activity) scale Concurrent therapy with topical corticosteroids and/or prednisone and/or antimalarials is permitted as defined in Exclusion Criteria. Concurrent therapy with methotrexate azathioprine, mycophenolate mofetil, or leflunomide is permitted as defined in Exclusion Criteria Must meet the following laboratory criteria: Hemoglobin &#8805; 12 g/dL White blood cell (WBC) count &#8805; 3000 /uL (&#8805; 3.0 X 10^9/L) and < 14,000/uL (< 14 X 10^9/L) Platelets &#8805; 100,000 /uL (&#8805; 100 X 10^9/L) Serum creatinine &#8804; 1.5 mg/dL (&#8804; 132.6 &#956;mol/L) Total bilirubin &#8804; 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) unless, in the opinion, of the investigator, the elevation is secondary to active muscle inflammation. 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. A FCBP must agree to have pregnancy tests every 28 days 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 Exclusion Criteria: History of inadequate response of cutaneous DM disease to greater than 2 of the following agents: methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, IVIG, leflunomide, cyclophosphamide. History of inadequate response to thalidomide for dermatomyositis skin disease. Receiving topical therapy within 14 days of Study Day 0 (including but not limited to topical corticosteroids, tacrolimus, pimecrolimus). Exceptions: low potency corticosteroids will be allowed as background therapy for treatment of the face and scalp as needed, but dose must be stable 14 days prior to Study Day 0 and throughout the study Concurrent therapy with prednisone (or equivalent dose of systemic corticosteroid) at greater than 10 mg daily. Concurrent therapy with more than one of the following agents: methotrexate, azathioprine, mycophenolate mofetil, leflunomide. Receiving the following dosages of medications during the study or within 28 days before Study Day 0: Hydroxychloroquine at >600 mg/day Chloroquine at >400 mg/day Methotrexate at >25 mg/week Mycophenolate mofetil at >3 g/day Azathioprine at >3 mg/kg/day Leflunomide at >20mg/day Treatment with the following biologic agents: Adalimumab, etanercept, efalizumab, or infliximab within 12 weeks of Study Day 0 and for the study duration IVIG within 12 weeks of Study Day 0 and for the study duration Rituximab within 9 months of Study Day 0 and for the study duration Alefacept within 24 weeks of Study Day 0 and for the study duration Have received fluctuating doses of any of the following medications 28 days before Study Day 0: methotrexate, mycophenolate mofetil, azathioprine, leflunomide, dapsone Have received fluctuating doses of hydroxychloroquine 2 months before Study Day 0 Have received fluctuating doses of chloroquine 3 months before Study Day 0 Have received fluctuating doses of prednisone within 14 days prior to Study Day 0 Received leflunomide >20 mg/day in the 6 months prior to Study Day 0 Treatment with any investigational drug therapy within 28 days before Study Day 0 or biologic therapies within 30 days or 5 half-lives of the biologic agent, whichever is longer, before Study Day 0 Currently receiving any of the following medications: Cyclophosphamide Intravenous immunoglobulin (IVIG) Any TNF inhibitor, including adalimumab, etanercept, infliximab, or certolizumab Rituximab Efalizumab Cyclosporine Oral FK506 (tacrolimus) Thalidomide History of any clinically significant (as determined by the investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major uncontrolled disease 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 Latent Mycobacterium tuberculosis infection as indicated by a positive Purified Protein Derivative (PPD) skin test. History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit and without documentation of successful treatment * Subjects who completed treatment at least 3 years prior to screening but lack documentation may not be enrolled in the study. Subjects who completed treatment at least 3 years prior to screening are allowed if successful treatment was completed at least 3 years prior to screening and is documented and available for verification History of incompletely treated latent 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 Any clinically significant abnormality on 12-lead ECG at screening Presence of hepatitis B surface antigens (HBsAg) or Hepatitis B core antibody positive at screening Antibodies to hepatitis C virus at screening History of human immunodeficiency virus (HIV) infection Malignancy or history of malignancy except for treated (i.e. cured) basal-cell skin carcinomas Abnormal chest x-ray findings other than that consistent with dermatomyositis-associated interstitial lung disease. Chest x-rays performed within 3 months prior to start of study drug are acceptable Any condition, including the presence of laboratory abnormalities, that 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apremilast<br>apremilast 20mg bid | Drug: Apremilast<br>* Apremilast 20mg PO BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Endpoint Analysis Will be Safety, as Measured by the Number of Adverse Events and Serious Adverse Events Occuring During 12 Weeks of Therapy and 4 Weeks of Followup. |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Secondary Outcome Measure Will be Efficacy, as Measured by the Number of Participants Experiencing a 30% Decreased in the CDASI-a Score at 12 Weeks. | This was an intent to treat analysis--dropouts are considered treatment failures. Missing data at 12 weeks imputed by last observation carried forward. | Data collected at 12 weeks after baseline visit. | 
| The Secondary Outcome Measure Will be Efficacy as Measured by the Mean Change in CDASI-activity at 12 Weeks | The CDASI (Cutaneous Dermatomyositis Activity and Severity Index) is a validated instrument to measure skin disease activity in dermatomyositis. A clinically meaningful change is a decrease of 4 points. All missing data are imputed using last observation carried forward. Calculation is performed as the score at 12 weeks minus the score at baseline. | Data collected at baseline at 12 weeks |