Clinical trial NCT00708916: Safety Study of Clinical and Immune Effects of Phosphodiesterase 4 (PDE-4) Inhibitor in Cutaneous Lupus Patients
Official title: Clinical and Immune-modulating Effects of CC-10004 in Discoid Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Discoid Lupus Erythematosus
Keywords: Cutaneous lupus
Intervention
Discoid lupus
Phosphodiesterase 5 inhibitor
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2008-07-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the clinical and immunological effects of the phosphodiesterase type 4 inhibitor, CC-10004, on skin inflammation associated with cutaneous lupus erythematosus.

Detailed description: Discoid cutaneous lupus is the most common cutaneous manifestation of lupus erythematosus, a chronic, immune mediated disease of unknown etiology. The immune processes underlying cutaneous lupus remain largely unexplored, but recent evidence suggests a role for dendritic cells (DCs), type 1 interferons (IFN) and Th1-type immune processes. Treatment of cutaneous lupus remains limited primarily to anti-malarials, with thalidomide an effective secondary agent. However, side effects associated with these treatments are potentially problematic with chronic use. Phosphodiesterases (PDE) are critical enzymes that degrade cAMP. In particular, PDE type 4 (PDE4) activity is found in inflammatory and immune cells, including DCs. The immune modulator CC-10004 is a PDE4 inhibitor with demonstrated low toxicity in phase I and II clinical studies with potential efficacy in cutaneous lupus. CC-10004 is a well-tolerated, selective PDE4 inhibitor with demonstrated inhibitory effects on Th1-type cytokines and other inflammatory mediators and is under development for the treatment of inflammatory and immune mediated conditions. Prior studies include pilot trials in psoriasis and exercise-induced asthma, with results suggesting clinical efficacy in the former study. This open label, pilot study of 16 weeks duration will explore the clinical and immune-modulating effects of CC-10004 in 10 cutaneous discoid lupus patients. Patients meeting study criteria will receive the drug for 12 weeks, followed by a 4-week washout period. Study visit time points will include weeks 0, 1, 2, 4, 6, 8, 10, 12 and 16, during which we will measure outcomes for clinical, immunological and safety parameters. To investigate early immunological changes occurring in response to treatment, we will also perform skin punch biopsies of lesional sites at week 0 and week 4 for immunohistochemical and molecular analysis.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of cutaneous discoid lupus by clinical and histopathological exam

Exclusion Criteria:

* Systemic lupus involving the internal organs
* Systemic vasculitis
* History of other clinically significant disease process
* History of HIV, hepatitis B or C
* Concurrent use of immune modulating therapy
* Evidence of incompletely treated tuberculosis
* Pregnant or lactating female

Primary outcomes:
measure: Cutaneous LE Diseases Area and Severity Index (CLASI) Score Based on Extent of Symptoms
timeFrame: 16 Weeks
Secondary outcomes:
measure: Dermatology Quality of Life Index (DQLI)
timeFrame: 16 Weeks
measure: Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
timeFrame: Weeks 1, 2, 4, 6, 8, 10, 12, 16
measure: Dermal and Circulating Blood Plasmacytoid Dendritic Cell Levels
timeFrame: Weeks 0, 4 (dermal and circulating); week 12 (circulating only)
measure: Dermal and Circulating Blood T Regulatory Cell Levels
timeFrame: Weeks 0, 4 (dermal and blood); Week 12 (blood only)
measure: Plasma Cytokine Levels
timeFrame: Weeks 0, 4, 12
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University Tisch Hospital
state: New York
Study officials:
affiliation: NYU Langone Health
name: Andrew G Franks, Jr., MD
role: PRINCIPAL_INVESTIGATOR
References: