Repigmentation Using Apremilast and Phototherapy In Diffuse VITILIGO
Repigmentation Using Apremilast and Phototherapy In Diffuse VITILIGO
Vitiligo is a depigmentation disorder affecting 0.5 to 2% of the general population. It is an
 acquired pigmentary disorder of the skin and mucous membranes that is characterized by
 circumscribed, depigmented macules and patches. Apremilast is a phosphosdiesterase 4 (PDE4)
 inhibitor that showed efficacy and very good tolerance in rheumatoid arthritis and psoriasis.
 Apremilast induces a potent activation of the cyclic AMP (cAMP) pathway leading to
 anti-inflammatory effect by decreasing the response of Th1 and Th17 lymphocytes.
 Interestingly, the cAMP pathway is also well demonstrated to be the main pathway for
 promoting melanogenesis and for inducing the differentiation and the proliferation of
 melanocytes. The principal aims is to compare, after 24 weeks of treatment, the efficacy of
 Apremilast at the label dosage in combination therapy with narrow band UVB versus placebo
 therapy with narrow band UVB for repigmentation in patients with non-segmental vitiligo.
 Patients with non-segmental vitiligo with BSA > 10% and patient with Vitiligo stable or
 slowly progressive for 3 months , seeking for treatment in the Department of Dermatology,
 University Hospital of Nice, France will be recruited into the study. The Patients are seen
 in consultation by the investigator, selection criteria are checked. All patients will
 receive full body narrow UVB treatment, twice weekly sessions of narrow UVB for 24 weeks.

 From W24 to W48

 -  All responders* will receive narrow UVB treatment according the French clinical use
 i.e.twice weekly sessions of narrowband UVB for 24 weeks.

 -  All responders* will be randomized to receive either apremilast** 30mg BID or placebo.

 -  Response is defined as an increase of at least 30 % in the VASI score at W24
 compare to baseline **Responders initially randomized in the placebo arm will
 benefit of the titration At week 24, the non responders patients will stop the
 treatment and the study after the 4 weeks observationnal follow-up (W28).

 Observational Follow-up Phase - W48 to W52 Four-week Observational Follow-up Phase for all
 subjects who complete the study (responders and non responders) or discontinue the study
 early.
Inclusion Criteria:

 -  Diagnosis of non-segmental vitiligo affecting at least 10% of BSA since at least 3
 months.

 -  Patient requiring a treatment by UVB

 -  For both female of childbearing potential and male patients: Use of an effective
 contraceptive method during the study period (see Annex 5 for details)

 -  Understand and voluntarily sign an informed consent document prior to any study
 related assessments/procedures being conducted

 -  Able to adhere to the study visit schedule and other protocol requirements

 -  Patient registered to the French Social Security

 Exclusion Criteria:

 1. Segmental or mixed vitiligo

 2. Other than vitiligo, history of any clinically significant (as determined by the
 Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic,
 renal, hematologic, immunologic disease, or other major uncontrolled disease.

 3. Any condition which would place the subject at unacceptable risk if he/she were to
 participate in the study.

 4. Any condition that confounds the ability to interpret data from the study.

 5. Pregnant or breast feeding, pregnancy urinary tests will be performed (see Annex 5 for
 details about pregnancy testing and contraception)

 6. History of allergy to any component of apremilast

 7. History of positive human immunodeficiency virus (HIV), or have congenital or acquired
 immunodeficiency (eg, common variable immunodeficiency disease)

 8. Active substance abuse or a history of substance abuse within 6 months prior to
 Screening

 9. Bacterial infections requiring treatment with oral or injectable antibiotics, or
 significant viral or fungal infections, within 4 weeks of Screening. Any treatment for
 such infections must have been completed at least 4 weeks prior to Screening.

 10. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or
 squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial
 neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence)

 11. Evidence of skin conditions that would interfere with clinical assessments

 12. Topical therapy within 2 weeks of randomization

 13. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light
 sources

 14. Prior treatment with apremilast

 15. Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)

 16. Use of any investigational drug within 4 weeks prior to randomization, or 5
 pharmacokinetic/pharmacodynamic half-lives,

 17. Patients assessed to be uncooperative

 18. Participants in other clinical studies

 19. Vulnerable people: pregnant or breast-feeding women (an urinary pregnancy test will be
 realized in every visit), minors, adults under guardianship or guardianship, deprived
 of freedom

 20. Patient with a rare hereditary disease such as galactose intolerance, Lapp lactase
 deficiency or glucose-galactose malabsorption syndrome

 21. Patient with severe renal insufficiency