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

February 10, 2021 updated by: NYU Langone Health

Clinical and Immune-modulating Effects of CC-10004 in Discoid Lupus Erythematosus

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • New York University Tisch Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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 Names:
  • Apremilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cutaneous LE Diseases Area and Severity Index (CLASI) Score Based on Extent of Symptoms
Time Frame: 16 Weeks

To evaluate the clinical response of cutaneous lupus patients to CC-10004. From J Invest Dermatol. 2005 Nov; 125(5): 889-894.doi: 10.1111/j.0022-202X.2005.23889.x:

The CLASI consists of two scores. One summarizes the activity of the disease on a scale from 0 to 30, higher score translates to more severe disease. The second is a measure of the damage done by the disease on a scale form 0 to 30, higher score translates to more severe disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. Each score is reported separately. Outcome measures are reported for each time point for each subject due to the low numbers of enrollment.
16 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dermatology Quality of Life Index (DQLI)
Time Frame: 16 Weeks
  1. To evaluate the clinical safety of CC-10004 in cutaneous lupus patients
  2. To determine the effect of CC-10004 on immune parameters in the skin

  3. To determine the effect of CC-10004 on immune parameters in the blood

    1. in vivo
    2. in vitro
  4. To determine the effect of CC-10004 on QOL and psychological outcome measures
16 Weeks
Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12, 16
  1. To evaluate the clinical safety of CC-10004 in cutaneous lupus patients
  2. To determine the effect of CC-10004 on immune parameters in the skin

  3. To determine the effect of CC-10004 on immune parameters in the blood

    1. in vivo
    2. in vitro
  4. To determine the effect of CC-10004 on QOL and psychological outcome measures
Weeks 1, 2, 4, 6, 8, 10, 12, 16
Dermal and Circulating Blood Plasmacytoid Dendritic Cell Levels
Time Frame: Weeks 0, 4 (dermal and circulating); week 12 (circulating only)
Weeks 0, 4 (dermal and circulating); week 12 (circulating only)
Dermal and Circulating Blood T Regulatory Cell Levels
Time Frame: Weeks 0, 4 (dermal and blood); Week 12 (blood only)
  1. To evaluate the clinical safety of CC-10004 in cutaneous lupus patients
  2. To determine the effect of CC-10004 on immune parameters in the skin

  3. To determine the effect of CC-10004 on immune parameters in the blood

    1. in vivo
    2. in vitro
  4. To determine the effect of CC-10004 on QOL and psychological outcome measures
Weeks 0, 4 (dermal and blood); Week 12 (blood only)
Plasma Cytokine Levels
Time Frame: Weeks 0, 4, 12
  1. To evaluate the clinical safety of CC-10004 in cutaneous lupus patients
  2. To determine the effect of CC-10004 on immune parameters in the skin

  3. To determine the effect of CC-10004 on immune parameters in the blood

    1. in vivo
    2. in vitro
  4. To determine the effect of CC-10004 on QOL and psychological outcome measures
Weeks 0, 4, 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: Andrew G Franks, Jr., MD, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (ACTUAL)

August 1, 2010

Study Completion (ACTUAL)

August 1, 2010

Study Registration Dates

First Submitted

July 1, 2008

First Submitted That Met QC Criteria

July 2, 2008

First Posted (ESTIMATE)

July 3, 2008

Study Record Updates

Last Update Posted (ACTUAL)

March 3, 2021

Last Update Submitted That Met QC Criteria

February 10, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-580

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Study Data/Documents

  1. Clinical Study Report
    Information identifier: PMID: 23134988
    Information comments:

    Apremilast for discoid lupus erythematosus: results of a phase 2, open-label, single-arm, pilot study. De Souza A, Strober BE, Merola JF, Oliver S, Franks AG Jr.

    J Drugs Dermatol. 2012 Oct;11(10):1224-6. PMID: 23134988

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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