<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03036995</url>
  </required_header>
  <id_info>
    <org_study_id>16-PP-06</org_study_id>
    <nct_id>NCT03036995</nct_id>
  </id_info>
  <brief_title>Repigmentation Using Apremilast and Phototherapy In Diffuse VITILIGO</brief_title>
  <acronym>Rapid Vitiligo</acronym>
  <official_title>Repigmentation Using Apremilast and Phototherapy In Diffuse VITILIGO RAPID VITILIGO</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Nice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Nice</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vitiligo is a depigmentation disorder affecting 0.5 to 2% of the general population. It is an&#xD;
      acquired pigmentary disorder of the skin and mucous membranes that is characterized by&#xD;
      circumscribed, depigmented macules and patches. Apremilast is a phosphosdiesterase 4 (PDE4)&#xD;
      inhibitor that showed efficacy and very good tolerance in rheumatoid arthritis and psoriasis.&#xD;
      Apremilast induces a potent activation of the cyclic AMP (cAMP) pathway leading to&#xD;
      anti-inflammatory effect by decreasing the response of Th1 and Th17 lymphocytes.&#xD;
      Interestingly, the cAMP pathway is also well demonstrated to be the main pathway for&#xD;
      promoting melanogenesis and for inducing the differentiation and the proliferation of&#xD;
      melanocytes. The principal aims is to compare, after 24 weeks of treatment, the efficacy of&#xD;
      Apremilast at the label dosage in combination therapy with narrow band UVB versus placebo&#xD;
      therapy with narrow band UVB for repigmentation in patients with non-segmental vitiligo.&#xD;
      Patients with non-segmental vitiligo with BSA &gt; 10% and patient with Vitiligo stable or&#xD;
      slowly progressive for 3 months , seeking for treatment in the Department of Dermatology,&#xD;
      University Hospital of Nice, France will be recruited into the study. The Patients are seen&#xD;
      in consultation by the investigator, selection criteria are checked. All patients will&#xD;
      receive full body narrow UVB treatment, twice weekly sessions of narrow UVB for 24 weeks.&#xD;
&#xD;
      From W24 to W48&#xD;
&#xD;
        -  All responders* will receive narrow UVB treatment according the French clinical use&#xD;
           i.e.twice weekly sessions of narrowband UVB for 24 weeks.&#xD;
&#xD;
        -  All responders* will be randomized to receive either apremilast** 30mg BID or placebo.&#xD;
&#xD;
             -  Response is defined as an increase of at least 30 % in the VASI score at W24&#xD;
                compare to baseline **Responders initially randomized in the placebo arm will&#xD;
                benefit of the titration At week 24, the non responders patients will stop the&#xD;
                treatment and the study after the 4 weeks observationnal follow-up (W28).&#xD;
&#xD;
      Observational Follow-up Phase - W48 to W52 Four-week Observational Follow-up Phase for all&#xD;
      subjects who complete the study (responders and non responders) or discontinue the study&#xD;
      early.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 20, 2017</start_date>
  <completion_date type="Actual">November 25, 2019</completion_date>
  <primary_completion_date type="Actual">November 8, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Score VASI</measure>
    <time_frame>at 24 weeks</time_frame>
    <description>Efficacy will be evaluated using the Vitiligo Area Scoring Index (VASI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Score VETF</measure>
    <time_frame>at 24 weeks</time_frame>
    <description>Efficacity will be also evaluated using the Vitiligo European Task Score (VETF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score VE</measure>
    <time_frame>at 24 weeks</time_frame>
    <description>Efficacy will be also evaluated using the Vitiligo Extent Score (VES)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Vitiligo</condition>
  <arm_group>
    <arm_group_label>Apremilast - Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will receive narrow UVB treatment and apremilast (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and apremilast during 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - Group B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient will receive UVB treatment and placebo (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment and placebo during 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast</intervention_name>
    <description>Patient will receive narrow UVB treatment and apremilast (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and apremilast during 24 weeks.</description>
    <arm_group_label>Apremilast - Group A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patient will receive narrow UVB treatment and placebo (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and placebo during 24 weeks.</description>
    <arm_group_label>Placebo - Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of non-segmental vitiligo affecting at least 10% of BSA since at least 3&#xD;
             months.&#xD;
&#xD;
          -  Patient requiring a treatment by UVB&#xD;
&#xD;
          -  For both female of childbearing potential and male patients: Use of an effective&#xD;
             contraceptive method during the study period (see Annex 5 for details)&#xD;
&#xD;
          -  Understand and voluntarily sign an informed consent document prior to any study&#xD;
             related assessments/procedures being conducted&#xD;
&#xD;
          -  Able to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
          -  Patient registered to the French Social Security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Segmental or mixed vitiligo&#xD;
&#xD;
          2. Other than vitiligo, history of any clinically significant (as determined by the&#xD;
             Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic,&#xD;
             renal, hematologic, immunologic disease, or other major uncontrolled disease.&#xD;
&#xD;
          3. Any condition which would place the subject at unacceptable risk if he/she were to&#xD;
             participate in the study.&#xD;
&#xD;
          4. Any condition that confounds the ability to interpret data from the study.&#xD;
&#xD;
          5. Pregnant or breast feeding, pregnancy urinary tests will be performed (see Annex 5 for&#xD;
             details about pregnancy testing and contraception)&#xD;
&#xD;
          6. History of allergy to any component of apremilast&#xD;
&#xD;
          7. History of positive human immunodeficiency virus (HIV), or have congenital or acquired&#xD;
             immunodeficiency (eg, common variable immunodeficiency disease)&#xD;
&#xD;
          8. Active substance abuse or a history of substance abuse within 6 months prior to&#xD;
             Screening&#xD;
&#xD;
          9. Bacterial infections requiring treatment with oral or injectable antibiotics, or&#xD;
             significant viral or fungal infections, within 4 weeks of Screening. Any treatment for&#xD;
             such infections must have been completed at least 4 weeks prior to Screening.&#xD;
&#xD;
         10. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or&#xD;
             squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial&#xD;
             neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence)&#xD;
&#xD;
         11. Evidence of skin conditions that would interfere with clinical assessments&#xD;
&#xD;
         12. Topical therapy within 2 weeks of randomization&#xD;
&#xD;
         13. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light&#xD;
             sources&#xD;
&#xD;
         14. Prior treatment with apremilast&#xD;
&#xD;
         15. Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)&#xD;
&#xD;
         16. Use of any investigational drug within 4 weeks prior to randomization, or 5&#xD;
             pharmacokinetic/pharmacodynamic half-lives,&#xD;
&#xD;
         17. Patients assessed to be uncooperative&#xD;
&#xD;
         18. Participants in other clinical studies&#xD;
&#xD;
         19. Vulnerable people: pregnant or breast-feeding women (an urinary pregnancy test will be&#xD;
             realized in every visit), minors, adults under guardianship or guardianship, deprived&#xD;
             of freedom&#xD;
&#xD;
         20. Patient with a rare hereditary disease such as galactose intolerance, Lapp lactase&#xD;
             deficiency or glucose-galactose malabsorption syndrome&#xD;
&#xD;
         21. Patient with severe renal insufficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Passeron Thierry, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Universitaire de Nice</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Nice - Dermatologie - Hôpital Archet</name>
      <address>
        <city>Nice</city>
        <state>Alpes-Maritimes</state>
        <zip>06</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>December 3, 2019</last_update_submitted>
  <last_update_submitted_qc>December 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitiligo</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apremilast</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03036995
org study id: 16-PP-06
nct id: NCT03036995
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Score VASI
time frame: at 24 weeks
description: Efficacy will be evaluated using the Vitiligo Area Scoring Index (VASI)
measure: Score VETF
time frame: at 24 weeks
description: Efficacity will be also evaluated using the Vitiligo European Task Score (VETF)
measure: Score VE
time frame: at 24 weeks
description: Efficacy will be also evaluated using the Vitiligo Extent Score (VES)
arm group label: Apremilast - Group A
arm group type: Experimental
description: Patient will receive narrow UVB treatment and apremilast (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and apremilast during 24 weeks.
arm group label: Placebo - Group B
arm group type: Placebo Comparator
description: Patient will receive UVB treatment and placebo (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment and placebo during 24 weeks.
intervention type: Drug
intervention name: Apremilast
description: Patient will receive narrow UVB treatment and apremilast (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and apremilast during 24 weeks.
arm group label: Apremilast - Group A
intervention type: Other
intervention name: Placebo
description: Patient will receive narrow UVB treatment and placebo (2 tablets for day) during 24 weeks. If the patient is responder (response is defined as an increase of at least 30 % in the VASI score at W24 compare to Baseline), he will receive narrow UVB treatment according the and placebo during 24 weeks.
arm group label: Placebo - Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Passeron Thierry, PhD
role: Principal Investigator
affiliation: Centre Hospitalier Universitaire de Nice
facility: 
country: France
responsible party type: Sponsor
mesh term: Vitiligo
mesh term: Apremilast