Safety Study of Clinical and Immune Effects of Phosphodiesterase 4 (PDE-4) Inhibitor in Cutaneous Lupus Patients

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Elizabeth Camacho, New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00708916
First received: July 1, 2008
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Discoid Lupus Erythematosus
Drug: CC-10004
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical and Immune-modulating Effects of CC-10004 in Discoid Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Cutaneous LE Diseases Area and Severity Index (CLASI) [ Time Frame: Weeks 4, 8, 12 and 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dermatology Quality of Life Index (DQLI) [ Time Frame: Week 4, 8, 12, 16 ] [ Designated as safety issue: No ]
  • Common Terminology Criteria for Adverse Events v3.0 (CTCAE) [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12, 16 ] [ Designated as safety issue: Yes ]
  • Dermal and circulating blood plasmacytoid dendritic cell levels [ Time Frame: Weeks 0, 4 (dermal and circulating); week 12 (circulating only) ] [ Designated as safety issue: No ]
  • Dermal and circulating blood T regulatory cell levels [ Time Frame: Weeks 0, 4 (dermal and blood); Week 12 (blood only) ] [ Designated as safety issue: No ]
  • Plasma cytokine levels [ Time Frame: Weeks 0, 4, 12 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: June 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Apremilast
CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Drug: CC-10004
20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Other Name: Apremilast

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708916

Locations
United States, New York
New York University Tisch Hospital
New York City, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Celgene Corporation
Investigators
Principal Investigator: Andrew G Franks, Jr., MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Elizabeth Camacho, PRS, New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00708916     History of Changes
Other Study ID Numbers: AP016
Study First Received: July 1, 2008
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
Cutaneous lupus
Intervention
Discoid lupus
Phosphodiesterase 5 inhibitor

Additional relevant MeSH terms:
Lupus Erythematosus, Discoid
Lupus Erythematosus, Systemic
Lupus Erythematosus, Cutaneous
Connective Tissue Diseases
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Phosphodiesterase 5 Inhibitors
Apremilast
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 01, 2014