Study of Apremilast in Atopic or Contact Dermatitis

Tracking Information
First Submitted Date ICMJE	June 30, 2009
First Posted Date ICMJE	July 2, 2009
Results First Submitted Date	October 28, 2010
Results First Posted Date	December 20, 2010
Last Update Posted Date	December 20, 2010
Study Start Date ICMJE	June 2009
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 23, 2010)	Number of Patients Achieving an Improvement (Decrease) in IGA (Investigator Global Assessment) by Two or More Points [ Time Frame: 12 weeks ]; Improvement in IGA (Investigator Global Assessment) by two or more points on a five point scale, with 0 being no disease activity and 5 being maximum disease activity, at week 12
Original Primary Outcome Measures ICMJE; (submitted: July 1, 2009)	To evaluate the clinical efficacy of apremilast, when taken for 12 weeks, in subjects with recalcitrant contact or atopic dermatitis. [ Time Frame: 12 weeks ]
Change History	Complete list of historical versions of study NCT00931242 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 23, 2010)	Number of Patients Achieving 75% Reduction in Eczema Area and Severity Index (EASI) Score at Week 12 in Reference to Week 0 [ Time Frame: 12 weeks ]EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, edema, lichenification, and excoriations/erosions are scored on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 to 6. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score.; Number of Patients Achieving 50% Reduction in Eczema Area and Severity Index (EASI) Score at Week 12 in Reference to Week 0 [ Time Frame: 12 weeks ]EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, edema, lichenification, and excoriations/erosions are scored on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 to 6. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score.
Original Secondary Outcome Measures ICMJE; (submitted: July 1, 2009)	To evaluate the safety of apremilast (20 mg PO, twice per day [BID] for 12 weeks) in subjects with recalcitrant contact or atopic dermatitis [ Time Frame: 12 weeks ]; To evaluate the change in Biomarkers in serum at Week 12 in reference to Week 0 (Baseline visit) in subjects with contact or atopic dermatitis taking apremilast [ Time Frame: 12 weeks ]; To determine the time to relapse in the Follow-up phase [ Time Frame: 4 weeks ]; To determine the effect of apremilast on quality-of-life [ Time Frame: 12 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study of Apremilast in Atopic or Contact Dermatitis
Official Title ICMJE	A Phase 2, Open-label, Investigator-Initiated Study to Evaluate the Safety and Efficacy of Apremilast in Subjects With Recalcitrant Contact or Atopic Dermatitis
Brief Summary	The objective of this study is to evaluate the efficacy of apremilast in patients with recalcitrant atopic or contact dermatitis.
Detailed Description	Atopic Dermatitis (AD) is a chronic, inflammatory skin disease characterized by dry, red, and itchy patches that can become thickened and lichenified with time. Contact Dermatitis, or Allergic Contact Dermatitis (ACD), is an eczematous reaction in response to an environmental allergen. The etiology of Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD) has not been completely elucidated, and new understandings of underlying mechanisms have expanded and focused treatment regimens and paradigms. Atopic Dermatitis (AD) is thought to be mediated by Th2 type T cells elaborating a number of cytokines which are blocked in vitro by apremilast. The chronic Atopic Dermatitis (AD) pathway may involve a change to Th1 cytokines. Genetic factors do not contribute as much to the course of Allergic Contact Dermatitis (ACD) as in Atopic Dermatitis (AD). Rather, Allergic Contact Dermatitis (ACD) is a type IV, T-cell mediated, delayed-hypersensitivity reaction that can be self-limited. Similar to Atopic Dermatitis (AD), a number of pro-inflammatory cytokines are involved in recruiting T cells preferentially to the skin: Th1 cytokines, Th2 cytokines, CD8 cytokines, and T-regulatory cytokines. These pathways in Allergic Contact Dermatitis (ACD) are activated by IFN-γ, driven by TNF-α, and as above, apremilast has been shown to block these cytokines in vitro. Current treatments for Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD) include skin care, trigger avoidance (especially in the case of ACD), topical corticosteroids, steroid sparing treatments, antihistamines, topical and systemic antibiotics, and ultraviolet light. For more recalcitrant Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD)cases, several immunosuppressive treatments exist. Subjects with recalcitrant Atopic Dermatitis (AD) or Allergic Contact Dermatitis (ACD)have exhausted conventional systemic treatment options because they do not respond to conventional systemic therapy or cannot use these agents due to side effects or cumulative toxicity. There is an urgent need to evaluate new therapeutic options in recalcitrant Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD). Very few of the available drugs for recalcitrant Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD) have reasonable efficacy and safety profiles in this condition, are easily available, or easy to administer. A new treatment strategy is needed for the treatment of recalcitrant contact or atopic dermatitis that would increase efficacy, minimize toxicity for both short and long-term treatment, and be easy to administer. The availability of alternative drug treatment(s) offering safe and effective short and long-term management would significantly benefit subjects with recalcitrant contact or atopic dermatitis. This study uses a novel oral agent (apremilast) that modulates multiple anti-inflammatory pathways through targeted phosphodiesterase type IV (PDE4) inhibition decreased expression of dermatitis. Apremilast has pharmacodynamic properties with a potential therapeutic benefit for treating inflammatory autoimmune disorders that involve elevated serum cytokine levels, including Atopic Dermatitis (AD) and Allergic Contact Dermatitis (ACD).
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Atopic Dermatitis; Allergic Contact Dermatitis
Intervention ICMJE	Drug: Apremilast; Apremilast is being evaluated at daily doses of 20 mg by mouth (PO) twice daily (BID) for 12 weeks of treatment (treatment phase) in subjects with recalcitrant plaque-type Atopic Dermatitis (AD) or Allergic Contact Ddermatitis (ACD).; Other Name: CC-10004 (apremilast)
Study Arms	Experimental: Apremilast; Apremilast is being evaluated at daily doses of 20 mg by mouth (PO) twice daily (BID) for 12 weeks of treatment (treatment phase) in subjects with recalcitrant plaque-type Atopic Dermatitis (AD) or Allergic Contact Ddermatitis (ACD).; Intervention: Drug: Apremilast
Publications *	Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. Review.; Novak N, Bieber T, Leung DY. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol. 2003 Dec;112(6 Suppl):S128-39. Review.; Girolomoni G, Sebastiani S, Albanesi C, Cavani A. T-cell subpopulations in the development of atopic and contact allergy. Curr Opin Immunol. 2001 Dec;13(6):733-7. Review.; Cavani A, Albanesi C, Traidl C, Sebastiani S, Girolomoni G. Effector and regulatory T cells in allergic contact dermatitis. Trends Immunol. 2001 Mar;22(3):118-20.; Cone RE, Li X, Sharafieh R, O'Rourke J, Vella AT. The suppression of delayed-type hypersensitivity by CD8+ regulatory T cells requires interferon-gamma. Immunology. 2007 Jan;120(1):112-9. Epub 2006 Oct 18.; Jung T, Stingl G. Atopic dermatitis: therapeutic concepts evolving from new pathophysiologic insights. J Allergy Clin Immunol. 2008 Dec;122(6):1074-81. doi: 10.1016/j.jaci.2008.09.042. Epub 2008 Nov 6. Review.; Belloni B, Andres C, Ollert M, Ring J, Mempel M. Novel immunological approaches in the treatment of atopic eczema. Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):423-7. doi: 10.1097/ACI.0b013e32830fb8fd. Review.; Harada D, Takada C, Nosaka Y, Takashima Y, Kobayashi K, Takaba K, Manabe H. Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. Int Immunopharmacol. 2009 Jan;9(1):55-62. doi: 10.1016/j.intimp.2008.09.011. Epub 2008 Oct 12.; Schmitt J, Langan S, Williams HC; European Dermato-Epidemiology Network. What are the best outcome measurements for atopic eczema? A systematic review. J Allergy Clin Immunol. 2007 Dec;120(6):1389-98. Epub 2007 Oct 1. Review.; Gottlieb AB, Strober B, Krueger JG, Rohane P, Zeldis JB, Hu CC, Kipnis C. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin. 2008 May;24(5):1529-38. doi: 10.1185/030079908X301866 . Epub 2008 Apr 16.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 1, 2009)	10
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	March 2010
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Must understand and voluntarily sign an informed consent form.; Must be male or female and aged ≥ 18 years at time of consent.; Must be able to adhere to the study visit schedule and other protocol requirements.; Must have a documented history of contact or atopic dermatitis for at least 3 months prior to screening visit. Subjects will be asked to bring records at the time of screening visit; if they do not bring these records, subjects will be asked to complete and sign a release of records for which will be sent to the subject's physician. The Investigators will review records to confirm eligibility prior to enrolling a subject into the study.; Subjects must fulfill criteria outlined in at least one of the following clinical categories: Unresponsive to standard systemic or topical therapy, as defined by clinical history, in the investigator's opinion, i.e. inadequate response to one or more adequate treatment course (s) of standard systemic therapy including but not limited to: topical steroids, ultraviolet light A [UVA], narrowband ultraviolet B (NBUVB), ultraviolet light B [UVB]. Intolerant to or cannot receive (e.g., contraindication to prescribe) standard systemic or topical therapy for contact or atopic dermatitis.; Must have a IGA score of at least moderate (3 on a 0 to 5 point scale) at screening.; Must meet the following laboratory criteria: White blood cell count ≥ 3000/ μL (3 x 109/L) and < 14,000/ μL (< 14 x 109/L) Platelet count > 100,000/ μL (100 x 109/L) Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L) AST (SGOT) and ALT (SGPT) ≤ 1.5 x upper limit of normal (ULN) Hemoglobin > 9 g/dL Total bilirubin ≤ 2.0 mg/dL; Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening. In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception while on study medication: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; vasectomized partner while on study.; A FCBP must agree to have pregnancy tests every 4 weeks while on study medication.; Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in sexual activity with FCBP while on study medication and for 84 days after taking the last dose of study medication. Exclusion Criteria: Inability to provide voluntary consent.; History of clinically significant (as determined by the investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major disease. Potential subjects with severe uncontrolled conditions, such as severe uncontrolled diabetes, will be excluded.; Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.; Pregnant or breastfeeding.; Systemic fungal infection.; History of active mycobacterial infection with any species (including Mycobacterium tuberculosis) within 3 years prior to screening visit. Subjects with Mycobacterium tuberculosis infection more than 3 years prior to screening visit are allowed if successful treatment was completed at least 3 years prior to randomization and is documented and available for verification.; Latent Mycobacterium tuberculosis infection as indicated by a positive Purified Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test and documented completion of treatment for latent TB are eligible. Subjects with a positive PPD skin test and not treated or no documentation of completion of treatment are ineligible.; If QuantiFERON® test is performed instead of the PPD test, only those with a negative QuantiFERON® test are allowed in the study.; History of incompletely treated Mycobacterium tuberculosis infection as indicated by: Subject's medical records documenting incomplete treatment for Mycobacterium tuberculosis. Subject's self-reported history of incomplete treatment for Mycobacterium tuberculosis.; History of recurrent bacterial infection (at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years).; Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest x-rays performed within 3 months prior to start of study drug are acceptable.; Contact or atopic Dermatitis flare within 30 days of screening, defined as a sudden intensification of contact or atopic dermatitis; Use of systemic therapy for contact or atopic dermatitis (including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine) within 14 days of Week 0 (Baseline).; Topical therapy (including but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin) within 7 days of Week 0 (Baseline). (Exception: Class VI or VII potency corticosteroids will be allowed [Appendix 18.8] for treatment of the palms, face, scalp, axillae, plantar surfaces and groin in accordance with the manufacturers suggested usage, except within 24 hours of a study visit. Non-medicated emollients [e.g., Eucerin®], and tar shampoo are also allowed.); Adalimumab, etanercept, efalizumab or infliximab use within 56 days of Week 0 (Baseline).; Alefacept use within 180 days of Week 0 (Baseline).; Phototherapy (PUVA, UVA,NB-UVB, UVB) within 14 days of Week 0 (Baseline).; Use of any investigational medication within 4 weeks prior to start of study drug or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer).; Any clinically significant abnormality on 12-lead ECG at screening.; History of congenital or acquired immunodeficiency (e.g., Common Variable Immunodeficiency [CVID]).; Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening.; History of Human Immunodeficiency Virus (HIV) infection.; Antibodies to Hepatitis C at screening.; Malignancy or history of malignancy (except for treated [i.e., cured] basal-cell skin carcinoma(s) or treated squamous-cell skin carcinomas).
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00931242
Other Study ID Numbers ICMJE	AD / CD; AP-ECZ-PI-0030 ( Other Grant/Funding Number: Celgene )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alice B. Gottlieb, MD, PhD, Tufts Medical Center
Study Sponsor ICMJE	Tufts Medical Center
Collaborators ICMJE	Celgene Corporation
Investigators ICMJE	Principal Investigator: Alice B. Gottlieb, M.D., PhD. Tufts Medical Center, Department of Dermatology
PRS Account	Tufts Medical Center
Verification Date	November 2010
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP