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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00708916
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Discoid Lupus Erythematosus	Drug: CC-10004	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical and Immune-modulating Effects of CC-10004 in Discoid Lupus Erythematosus
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Cutaneous LE Diseases Area and Severity Index (CLASI) Score Based on Extent of Symptoms [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.

Secondary Outcome Measures

1. Dermatology Quality of Life Index (DQLI) [16 Weeks]

   To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures

2. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) [Weeks 1, 2, 4, 6, 8, 10, 12, 16]

   To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures

3. Dermal and Circulating Blood Plasmacytoid Dendritic Cell Levels [Weeks 0, 4 (dermal and circulating); week 12 (circulating only)]

4. Dermal and Circulating Blood T Regulatory Cell Levels [Weeks 0, 4 (dermal and blood); Week 12 (blood only)]

   To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures

5. Plasma Cytokine Levels [Weeks 0, 4, 12]

   To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	New York University Tisch Hospital	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health
• Celgene Corporation

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00708916
• Other Study ID Numbers: 07-580
• First Posted: Jul 3, 2008
• Last Update Posted: Mar 3, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NYU Langone Health: Cutaneous lupus; Intervention; Discoid lupus; Phosphodiesterase 5 inhibitor
• Additional relevant MeSH terms: Lupus Erythematosus, Discoid; Apremilast

Study Results

Participant Flow

Recruitment Details	Drs. Franks/Oliver and other physician (attendings) would refer subjects to the unit if they were interested.
Pre-assignment Detail	Screen Fail subjects were excluded from participation in trial.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Period Title: Overall Study
STARTED	12
COMPLETED	8
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment CC-10004: 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 87.5%
Male	1 12.5%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The PI and study team has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data for primary outcome measure are available

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

2. Secondary Outcome

Title	Dermatology Quality of Life Index (DQLI)
Description	To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Secondary outcome measures were not measured in this study.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PI no longer with institution. No secondary outcome measure data available for reporting.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

4. Secondary Outcome

Title	Dermal and Circulating Blood Plasmacytoid Dendritic Cell Levels
Time Frame	Weeks 0, 4 (dermal and circulating); week 12 (circulating only)

Outcome Measure Data

Analysis Population Description

PI no longer with institution. No secondary outcome measure data available for reporting.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

5. Secondary Outcome

Title	Dermal and Circulating Blood T Regulatory Cell Levels
Description	To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures
Time Frame	Weeks 0, 4 (dermal and blood); Week 12 (blood only)

Outcome Measure Data

Analysis Population Description

PI no longer with institution. No secondary outcome measure data available for reporting.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

6. Secondary Outcome

Title	Plasma Cytokine Levels
Description	To evaluate the clinical safety of CC-10004 in cutaneous lupus patients To determine the effect of CC-10004 on immune parameters in the skin To determine the effect of CC-10004 on immune parameters in the blood in vivo in vitro To determine the effect of CC-10004 on QOL and psychological outcome measures
Time Frame	Weeks 0, 4, 12

Outcome Measure Data

Analysis Population Description

PI no longer with institution. No secondary outcome measure data available for reporting.

Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment CC-10004: 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
Measure Participants	0

Adverse Events

Time Frame	2 years
Arm/Group Title	Apremilast
Arm/Group Description	CC-10004 20 mg twice daily by mouth for 12 weeks, followed by a 4 week washout period and final assessment
All Cause Mortality
	Apremilast
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Apremilast
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Nervous system disorders
Neuraopathy Sensory	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Lichenoid Dermatitis	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Apremilast
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Gastrointestinal disorders
Nausea	4/8 (50%)	4
Diarrhea	1/8 (12.5%)	1
Nervous system disorders
Headache	2/8 (25%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.