<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/NCT03240627</url>
  </required_header>
  <id_info>
    <org_study_id>RAAINBOW</org_study_id>
    <nct_id>NCT03240627</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of LH-8 in Paediatric Alopecia Areata</brief_title>
  <acronym>AA</acronym>
  <official_title>Double-blind, Vehicle-controlled, Randomised, Multi-centre Study to Evaluate the Efficacy and Safety of LH-8 Cutaneous Solution in Children and Adolescents With Moderate to Severe Scalp Alopecia Areata.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Legacy Healthcare SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Legacy Healthcare SA</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Double-blind, randomised, multi-centre study to evaluate the efficacy and safety of LH-8&#xD;
      cutaneous solution versus placebo in children and adolescents with moderate to severe scalp&#xD;
      alopecia areata.&#xD;
&#xD;
      Phase 2/3 study performed in France, Germany, Bulgaria and India in 100 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods / trial design:&#xD;
&#xD;
      Randomised, double-blind, vehicle-controlled multicentre trial in parallel groups.&#xD;
&#xD;
      At screening (Visit 0), subjects will discontinue their previous treatment for alopecia&#xD;
      areata, if any. Screening period will last up to 28 days. The 24-week treatment phase will&#xD;
      include assessment Visits 1 to 3, which will take place at 12-week intervals. At assessment&#xD;
      Visit 1, eligible subjects will be randomly assigned in a 2:1 ratio to receive LH-8 cutaneous&#xD;
      solution or vehicle (placebo) twice daily for a 24 week treatment period. During the&#xD;
      treatment phase the subjects will complete daily their drug diaries. The post-treatment&#xD;
      safety and efficacy follow-up phase will include Visit 4 and Visit 5, 12 and 24 weeks after&#xD;
      end of treatment, respectively.&#xD;
&#xD;
      Subjects (as applicable) and parents will be instructed to contact the investigator, if an&#xD;
      event on scalp (intolerance) occurs during the treatment or post-treatment period. They may&#xD;
      be asked to come to the site for an unscheduled visit, in order to perform additional&#xD;
      examinations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">September 14, 2022</completion_date>
  <primary_completion_date type="Actual">March 14, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <intervention_model_description>Randomised, double-blind, vehicle-controlled multicentre trial in parallel groups.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relative change in scalp alopecia areata severity scores (SALT) from baseline value to be assessed after 24 weeks of treatment.</measure>
    <time_frame>24 weeks treatment</time_frame>
    <description>Visual assessment and global standardised scalp photographs for SALT evaluation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute change in SALT score from baseline at the end of 24 weeks' treatment period.</measure>
    <time_frame>24 weeks treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of the responders, i.e. subjects achieving at least a 40% relative reduction in SALT score from baseline at the end of 24 weeks' treatment period.</measure>
    <time_frame>24 weeks treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General physical examination findings, including irritation of eyes and skin</measure>
    <time_frame>24 weeks treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual assessment and global standardised scalp photographs for SALT evaluation.</measure>
    <time_frame>After 12 and 24 weeks treatment</time_frame>
    <description>Evaluation of duration of treatment effect in responders, measured as relative SALT score changes from Visit 3 (end of treatment) after 12 weeks (Visit 4) and 24 weeks (Visit 5) of treatment-free period. (Visual assessment and global standardised scalp photographs for SALT evaluation.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of treatment effect on hair follicles in non-alopecic areas by quantifying the number of new alopecic areas.</measure>
    <time_frame>24 weeks treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the rate of spontaneous hair regrowth.</measure>
    <time_frame>For 6-12 months</time_frame>
    <description>Assessment of the rate of spontaneous hair regrowth in placebo treated subjects with alopecia areata active for 6-12 months compared to those with alopecia areata active for more than 12 months. (Visual assessment and global standardised scalp photographs for SALT evaluation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Absolute and relative change from baseline in Children's Dermatology Life Quality Index (CDLQI) scores.</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in percentage of subjects from baseline by the severity banding CDLQI scores.</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentages of subjects by EuroQol Five Dimensions Youth Questionnaire (EQ-5D-Y) dimensions and levels at Visits 1-5.</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative change of the EQ-Visual Analogue Scale (EQ-VAS) scores from baseline</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Paediatric Alopecia Areata Patient Benefit Index (PAAPBI) scores at Visits 1 to 5.</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Alopecia Areata</condition>
  <condition>Pediatric Disorder</condition>
  <arm_group>
    <arm_group_label>LH-8 cutaneous solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LH-8 cutaneous solution (0.126 mL per spray) applied to the whole scalp:</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo cutaneous solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo cutaneous solution (0.126 mL per spray) applied to the whole scalp:</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LH-8</intervention_name>
    <description>LH-8 cutaneous solution</description>
    <arm_group_label>LH-8 cutaneous solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo cutaneous solution</description>
    <arm_group_label>Placebo cutaneous solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Male and female children and adolescents aged 2 to less than 18 years with active alopecia&#xD;
        areata involving 25% to 95% of the scalp between 6 months and 3 years in duration.&#xD;
&#xD;
        Diagnosis and main criteria for inclusion: Male and female children and adolescents aged 2&#xD;
        to less than 18 years with active alopecia areata involving 25% to 95% of the scalp between&#xD;
        6 months and 3 years in duration.&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          1. Male and female children and adolescents aged 2 to less than 18 years.&#xD;
&#xD;
          2. Active scalp alopecia areata, involving 25% to 95% of the scalp (as measured by SALT&#xD;
             score at screening).&#xD;
&#xD;
          3. Duration of hair loss between 6 months and 3 years.&#xD;
&#xD;
          4. Female subjects of childbearing potential (postmenarcheal) must have a negative urine&#xD;
             pregnancy test at screening. Females of childbearing potential must either not be&#xD;
             sexually active or be using an adequate birth control method throughout the duration&#xD;
             of the study.&#xD;
&#xD;
          5. All subjects taking thyroid medication or hormonal therapy must be on a stable dose&#xD;
             for 6 months and maintain such throughout the study.&#xD;
&#xD;
          6. Subjects must be willing to maintain the same hair style, including hair dye,&#xD;
             throughout the study period.&#xD;
&#xD;
          7. Written informed consent signed by parent(s) or legally authorized representative and&#xD;
             assent or consent signed by the subjects, if applicable, according to national&#xD;
             regulations prior to any protocol specific procedures.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Hypersensitivity or intolerance to any active IMP substances (onion, citrus, caffeine,&#xD;
             theobromine) or excipients (glycerine, betaine or ethanol).&#xD;
&#xD;
          2. Any cause of hair loss other than alopecia areata.&#xD;
&#xD;
          3. Active scalp inflammation except alopecia areata.&#xD;
&#xD;
          4. Nevi, cutaneous or non-cutaneous lesions currently undiagnosed but suspicious for&#xD;
             malignancy.&#xD;
&#xD;
          5. Female adolescents who are pregnant or who are nursing or plan pregnancy during the&#xD;
             trial period.&#xD;
&#xD;
          6. Use of topical medication (listed in protocol Section 10.7.1) within 2 weeks prior to&#xD;
             Visit 1.&#xD;
&#xD;
          7. Use of systemic alopecia areata therapies (e.g. prednisone, cyclosporine,&#xD;
             methotrexate), including use of these medications for other indications, and&#xD;
             intralesional corticosteroids within 1 month prior to Visit 1.&#xD;
&#xD;
          8. Administration of hydroxychloroquine or finasteride within two months prior to Visit&#xD;
             1.&#xD;
&#xD;
          9. Use of phototherapy, laser therapy or excimer laser therapy on the scalp within three&#xD;
             months prior to Visit 1.&#xD;
&#xD;
         10. Use of infliximab within two months, adalimumab within three months, and ustekinumab&#xD;
             within four months prior to Visit 1 or use of other TNF inhibitors and biologic agents&#xD;
             within one month or five half-lives before Visit 1, whichever is longer.&#xD;
&#xD;
         11. Prior treatment with IMP.&#xD;
&#xD;
         12. Evidence or history of alcohol, medication or drug abuse.&#xD;
&#xD;
         13. History of systemic or cutaneous medical, or psychiatric disease which will put&#xD;
             subject at risk or interfere with assessments.&#xD;
&#xD;
         14. Participation in any other clinical trial within 30 days prior to Visit 1.&#xD;
&#xD;
         15. Subject is in a dependent relationship (e.g. relative or family member) with the&#xD;
             investigator's or sponsor's staff.&#xD;
&#xD;
         16. Any other condition or circumstance that, in the opinion of the investigator, could&#xD;
             compromise the subject's ability to comply with the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulrike BLUME-PEYTAVI, Prof. Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Charité-Universitätsmedizin Berlin, Dept Dermatology, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pascal REYGAGNE, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sabouraud Center, Saint-Louis Hospital, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yvan Botev, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>&quot;Diagnostic-consulting center XXIV-Sofia&quot;, Bulgaria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Horia Beti, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>SC Centrul Medical Sana SRL, Romania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Multicenter Clinical Trials</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Sabourand - Hospital Saint-Louis, 1, Avenue Claude Vellefaux</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <state>Berlin,</state>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>France</country>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>December 25, 2022</last_update_submitted>
  <last_update_submitted_qc>December 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2022</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>Alopecia</mesh_term>
    <mesh_term>Alopecia Areata</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03240627
org study id: RAAINBOW
nct id: NCT03240627
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Double-blind, randomised, multi-centre study to evaluate the efficacy and safety of LH-8
      cutaneous solution versus placebo in children and adolescents with moderate to severe scalp
      alopecia areata.

      Phase 2/3 study performed in France, Germany, Bulgaria and India in 100 patients.
Methods / trial design:

      Randomised, double-blind, vehicle-controlled multicentre trial in parallel groups.

      At screening (Visit 0), subjects will discontinue their previous treatment for alopecia
      areata, if any. Screening period will last up to 28 days. The 24-week treatment phase will
      include assessment Visits 1 to 3, which will take place at 12-week intervals. At assessment
      Visit 1, eligible subjects will be randomly assigned in a 2:1 ratio to receive LH-8 cutaneous
      solution or vehicle (placebo) twice daily for a 24 week treatment period. During the
      treatment phase the subjects will complete daily their drug diaries. The post-treatment
      safety and efficacy follow-up phase will include Visit 4 and Visit 5, 12 and 24 weeks after
      end of treatment, respectively.

      Subjects (as applicable) and parents will be instructed to contact the investigator, if an
      event on scalp (intolerance) occurs during the treatment or post-treatment period. They may
      be asked to come to the site for an unscheduled visit, in order to perform additional
      examinations.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised, double-blind, vehicle-controlled multicentre trial in parallel groups.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Relative change in scalp alopecia areata severity scores (SALT) from baseline value to be assessed after 24 weeks of treatment.
time frame: 24 weeks treatment
description: Visual assessment and global standardised scalp photographs for SALT evaluation.
measure: Absolute change in SALT score from baseline at the end of 24 weeks' treatment period.
time frame: 24 weeks treatment
measure: Proportion of the responders, i.e. subjects achieving at least a 40% relative reduction in SALT score from baseline at the end of 24 weeks' treatment period.
time frame: 24 weeks treatment
measure: Adverse events
time frame: 48 weeks
measure: General physical examination findings, including irritation of eyes and skin
time frame: 24 weeks treatment
measure: Visual assessment and global standardised scalp photographs for SALT evaluation.
time frame: After 12 and 24 weeks treatment
description: Evaluation of duration of treatment effect in responders, measured as relative SALT score changes from Visit 3 (end of treatment) after 12 weeks (Visit 4) and 24 weeks (Visit 5) of treatment-free period. (Visual assessment and global standardised scalp photographs for SALT evaluation.)
measure: Assessment of treatment effect on hair follicles in non-alopecic areas by quantifying the number of new alopecic areas.
time frame: 24 weeks treatment
measure: Assessment of the rate of spontaneous hair regrowth.
time frame: For 6-12 months
description: Assessment of the rate of spontaneous hair regrowth in placebo treated subjects with alopecia areata active for 6-12 months compared to those with alopecia areata active for more than 12 months. (Visual assessment and global standardised scalp photographs for SALT evaluation).
measure: • Absolute and relative change from baseline in Children's Dermatology Life Quality Index (CDLQI) scores.
time frame: 48 weeks
measure: Change in percentage of subjects from baseline by the severity banding CDLQI scores.
time frame: 48 weeks
measure: Percentages of subjects by EuroQol Five Dimensions Youth Questionnaire (EQ-5D-Y) dimensions and levels at Visits 1-5.
time frame: 48 weeks
measure: Absolute and relative change of the EQ-Visual Analogue Scale (EQ-VAS) scores from baseline
time frame: 48 weeks
measure: Evaluation of the Paediatric Alopecia Areata Patient Benefit Index (PAAPBI) scores at Visits 1 to 5.
time frame: 48 weeks
arm group label: LH-8 cutaneous solution
arm group type: Experimental
description: LH-8 cutaneous solution (0.126 mL per spray) applied to the whole scalp:
arm group label: Placebo cutaneous solution
arm group type: Placebo Comparator
description: Placebo cutaneous solution (0.126 mL per spray) applied to the whole scalp:
intervention type: Drug
intervention name: LH-8
description: LH-8 cutaneous solution
arm group label: LH-8 cutaneous solution
intervention type: Drug
intervention name: Placebo
description: Placebo cutaneous solution
arm group label: Placebo cutaneous solution
criteria: 
gender: All
minimum age: 2 Years
maximum age: 18 Years
healthy volunteers: No
last name: Ulrike BLUME-PEYTAVI, Prof. Dr.
role: Study Chair
affiliation: Charité-Universitätsmedizin Berlin, Dept Dermatology, Germany
last name: Pascal REYGAGNE, Dr.
role: Principal Investigator
affiliation: Sabouraud Center, Saint-Louis Hospital, France
last name: Yvan Botev, Dr.
role: Principal Investigator
affiliation: "Diagnostic-consulting center XXIV-Sofia", Bulgaria
last name: Horia Beti, Dr.
role: Principal Investigator
affiliation: SC Centrul Medical Sana SRL, Romania
facility: 
facility: 
facility: 
country: Bulgaria
country: France
country: Germany
responsible party type: Sponsor
mesh term: Alopecia
mesh term: Alopecia Areata
sharing ipd: No