The Efficacy and Safety of CC-10004 in Chronic Cutaneous Sarcoidosis

Study Overview
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Brief Summary
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To determine whether CC-10004, a phosphodiesterase inhibitor, is useful in treating chronic cutaneous sarcoidosis.

Detailed Description
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This will be an open label, phase II trial of CC-10004 for chronic cutaneous sarcoidosis. It will include two centers (University of Cincinnati and Medical University of South Carolina). The study will evaluate patients with chronic disease who are on a stable treatment regimen and have no significant change in their Sarcoidosis Skin Activity and Severity Index score (SASI) at two visits at least one month apart.

Official Title
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The Efficacy and Safety of CC-10004 in Chronic Cutaneous Sarcoidosis

Conditions
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Sarcoidosis, Cutaneous Sarcoidosis

Intervention / Treatment
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* Drug: CC-100004


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 male or female and aged ≥ 18 years at time of consent Must be able to adhere to the study visit schedule and other protocol requirements Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, biopsy finding granulomas, and no alternative for the cause of the granulomas, such as tuberculosis Patients must have chronic cutaneous skin lesions while taking chronic therapy (corticosteroids, methotrexate (max 10mg/week), azathioprine, hydroxychloroquine, cyclophosphamide, minocycline, doxycycline and chloroquine), in which the dose has not been altered in the three months prior to starting the study. Must have two visits within the previous 1-6 months (at least one month apart) with stable skin lesions, such as a SASI score was within one point for each of the features of the lesion. Must meet the following laboratory criteria: Hemoglobin > 9 g/dL Hematocrit ≥ 27% White blood cell (WBC) count ≥ 3000 (≥ 3.0 X 109/L) and < 20,000 (< 20 X 109/L) Neutrophils ≥ 1500 (≥ 1.5 X 109/L) Platelets ≥ 100,000 (≥ 100 X 109/L) Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 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) 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 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 any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases (not including pulmonary sarcoidosis) 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 lactating female History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated. History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T-SPOT®.TB, QuantiFERON Gold®]. Clinically significant abnormality on the chest x-ray (CXR) at screening not due to sarcoidosis Use of any investigational medication within 28 days. Any clinically significant abnormality on 12-lead ECG at screening Positive human immunodeficiency virus (HIV), hepatitis B, or hepatitis C laboratory test result indicating active infection at screening History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas) Use of infliximab, etanercept, adalimumab, pentoxifylline, or thalidomide in the prior three months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Open label drug<br>Drug: CC-100004 After the screening period, subjects will receive CC-10004 20mg by mouth BID for 84 days. The 84-day duration of treatment is expected to provide adequate time to assess the short-term efficacy and safety of CC-10004 in a population of subjects with chronic cutaneous sarcoidosis | Drug: CC-100004<br>* After the screening period, subjects will receive CC-10004 20mg by mouth BID for 84 days. The 84-day duration of treatment is expected to provide adequate time to assess the short-term efficacy and safety of CC-10004 in a population of subjects with chronic cutaneous sarcoidosis.<br>* Other names: Aprelimast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in skin lesions as assessed by a Sarcoidosis Skin Activity and Severity Index (SASI) . |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety (type, frequency, severity, and relationship of adverse events to study treatment) of CC-10004 in patients with chronic cutaneous sarcoidosis. |  | 6 months | 
| Improvement of global score of sarcoidosis using a visual analogue scale (VAS) by both the patient and a separate VAS by the physician. |  | 6 months | 
| Change in the quality of life using the Sarcoidosis Health Questionnaire and Short Form-36 (SF-36). |  | 6 months | 
| Change in genomic and proteomic expression of cytokines in paired skin biopsies (non-facial lesions). |  | 6 months | 
| Improvement in pulmonary status, specifically the six-minute walk test, dyspnea score, and forced vital capacity (FVC). |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcodiosis, tumor necrosis factor