To Evaluate the Preliminary Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CC-11050 in Subjects With Discoid Lupus Erythematosus and Subacute Cutaneous Lupus Erythematosus

Study Overview
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Brief Summary
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This is the first study in cutaneous lupus erythematosus subjects to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of CC-11050.

Official Title
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A Phase 2, Pilot, Multicenter, Sequential, Ascending Dose Study to Evaluate the Preliminary Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CC-11050 in Subjects With Discoid Lupus Erythematosus and Subacute Cutaneous Lupus Erythematosus

Conditions
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Cutaneous Lupus Erythematosus

Intervention / Treatment
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* Drug: CC-11050
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with a clinical diagnosis of discoid lupus erythematosus or sub acute lupus erythematosus for > 16 weeks prior to screening and consistent histological findings on skin biopsy based on Gilliam classification who are candidates for systemic therapies (as determined by the Investigator) Must, in the opinion of the Investigator, have active skin lesions of sufficient severity at Screening and Baseline (a Cutaneous Lupus Area and Severity Index Activity Score of ≥ 10) All subjects taking hydroxychloroquine, chloroquine or quinacrine during the study must have documentation of an ophthalmologic exam performed within 24 weeks of the Baseline Visit. Must meet the following laboratory criteria: White blood cell count ≥3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L) Absolute neutrophil count (ANC) > 1500 cells/μL (1.5 x 109/L) Platelet count ≥ 100,000/μL (≥ 100 x 109/L) Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L) Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 1.5 X upper limit of normal (ULN) Total bilirubin < 2mg/dL Hemoglobin > 11 g/dL Key Exclusion Criteria Participation in multiple CC-11050 cohorts or previous exposure to CC-11050 Presence or history of SLE based on investigators' clinical evaluation where subject exhibits medically significant (as determined by the Investigator) LE-related pleuritis, pericarditis, neurologic, renal and/or other major SLE-related organ system involvement(SLE-related to SLE joint involvement is acceptable). Use of topical or any local therapy known to possibly benefit discoid lupus erythematosus or SCLE sub acute lupus erythematosus within 2 weeks of the Screening Visit Use of concomitant disease modifying anti-rheumatic drugs (DMARDs) with the exception of anti-malarials within 4 weeks of screening- Use of topical or any local therapy known to possibly benefit discoid lupus erythematosus or SCLE sub acute lupus erythematosus within 2 weeks of the Screening Visit Use of immunosuppressives (eg, azathioprine, mycophenolate mofetil, methotrexate, etc.) within 4 weeks of screening

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>CC-11050 (50 milligrams twice per day and Placebo) | Drug: CC-11050<br>* Cohort 1: 50 milligrams twice per day for 4 weeks Cohort 2: 100 milligrams twice per day for 8 weeks Cohort 3: 200 milligrams twice per day for 12 week<br>Other: Placebo<br> <br> |
| Experimental: Cohort 2<br>CC-11050 (100 milligrams twice per day and Placebo) | Drug: CC-11050<br>* Cohort 1: 50 milligrams twice per day for 4 weeks Cohort 2: 100 milligrams twice per day for 8 weeks Cohort 3: 200 milligrams twice per day for 12 week<br>Other: Placebo<br> <br> |
| Experimental: Cohort 3<br>CC-11050 (200 milligrams twice per day and Placebo) | Drug: CC-11050<br>* Cohort 1: 50 milligrams twice per day for 4 weeks Cohort 2: 100 milligrams twice per day for 8 weeks Cohort 3: 200 milligrams twice per day for 12 week<br>Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory values from chemistry, hematology, urinalysis, inflammation/immunology panel that reveal clinically significant abnormalities and that may constitute a safety concern |  | Up to 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) | To describe the area under the curve (AUC) of CC-11050 and M15 in plasma | Up to 21 weeks | 
| To assess the clinical response rate of CC-11050 in subjects with discoid lupus erythematosus or sub acute lupus erythematosus using the Cutaneous Lupus Area and Severity Index Activity Score following 12-weeks of treatment |  | 12 weeks | 
| Pharmacokinetics (PK) | To describe the peak serum concentration (Cmax) of CC-11050 and M15 in plasma | Up to 21 weeks | 
| Pharmacokinetics | To describe the lowest serum concentration (Cmin)of CC-11050 and M15 in plasma | Up to 21 weeks | 
| Pharmacokinetics (PK) | To describe the time after administration of a drug when the maxiumum plasma concentration is reached (tmax) of CC-11050 and M15 in plasma | Up to 21 weeks | 
| Pharmacokinetics (PK) | To describe the half life (t1/2) of CC-11050 and M15 in plasma | Up to 21 weeks | 
| Pharmacokinetics (PK) | To describe the oral clearance (CL/F) of CC-11050 and M15 in plasma | Up to 21 weeks | 
| Pharmacokinetics (PK) | To describe the volume of distribution (Vz/F) of CC-11050 and M15 in plasma | Up to 21 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus, cutaneous lupus erythematosus, subacute lupus erythematosus, discoid lupus erythematosus