Efficacy and Safety of LH-8 in Paediatric Alopecia Areata (AA)

• ClinicalTrials.gov Identifier: NCT03240627
• Recruitment Status: Completed
• First Posted: August 7, 2017
• Last Update Posted: December 12, 2023
• Sponsor: Legacy Healthcare SA
• Information provided by (Responsible Party): Legacy Healthcare SA

Tracking Information

• First Submitted Date: July 26, 2017
• First Posted Date: August 7, 2017
• Last Update Posted Date: December 12, 2023
• Actual Study Start Date: February 1, 2018
• Actual Primary Completion Date: March 14, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2017)

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 ]

Visual assessment and global standardised scalp photographs for SALT evaluation.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2019)

• Absolute change in SALT score from baseline at the end of 24 weeks' treatment period. [ Time Frame: 24 weeks treatment ]
• 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 ]
• Adverse events [ Time Frame: 48 weeks ]
• General physical examination findings, including irritation of eyes and skin [ Time Frame: 24 weeks treatment ]
• Visual assessment and global standardised scalp photographs for SALT evaluation. [ Time Frame: After 12 and 24 weeks treatment ]
  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.)
• Assessment of treatment effect on hair follicles in non-alopecic areas by quantifying the number of new alopecic areas. [ Time Frame: 24 weeks treatment ]
• Assessment of the rate of spontaneous hair regrowth. [ Time Frame: For 6-12 months ]
  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).
• • Absolute and relative change from baseline in Children's Dermatology Life Quality Index (CDLQI) scores. [ Time Frame: 48 weeks ]
• Change in percentage of subjects from baseline by the severity banding CDLQI scores. [ Time Frame: 48 weeks ]
• Percentages of subjects by EuroQol Five Dimensions Youth Questionnaire (EQ-5D-Y) dimensions and levels at Visits 1-5. [ Time Frame: 48 weeks ]
• Absolute and relative change of the EQ-Visual Analogue Scale (EQ-VAS) scores from baseline [ Time Frame: 48 weeks ]
• Evaluation of the Paediatric Alopecia Areata Patient Benefit Index (PAAPBI) scores at Visits 1 to 5. [ Time Frame: 48 weeks ]

Original Secondary Outcome Measures (submitted: August 2, 2017)

• 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 ]
• Absolute change in SALT score from baseline at the end of 24 weeks' treatment period. [ Time Frame: 24 weeks treatment ]
• Adverse events [ Time Frame: 48 weeks ]
• General physical examination findings, including irritation of eyes and skin [ Time Frame: 48 weeks ]
• Evaluation of duration of treatment effect in responders, measured as relative SALT score changes [ Time Frame: 48 weeks ]
  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.
• Assessment of treatment effect on hair follicles in non-alopecic areas [ Time Frame: 48 weeks ]
  By quantifying the number of new alopecic areas.
• Assessment of the rate of spontaneous hair regrowth in placebo treated subjects [ Time Frame: 48 weeks ]
  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)
• Absolute and relative change from baseline in Children's Dermatology Life Quality Index (CDLQI) scores [ Time Frame: 48 weeks ]
• Change in percentage of subjects from baseline by the severity banding CDLQI scores. [ Time Frame: 48 weeks ]
• Percentages of subjects by EuroQol Five Dimensions Youth Questionnaire (EQ-5D-Y) dimensions and levels at Visits 1 to 5 [ Time Frame: 48 weeks ]
• Absolute and relative change of the EQ-Visual Analogue Scale (EQ-VAS) scores from baseline [ Time Frame: 48 weeks ]
• Evaluation of the Paediatric Alopecia Areata Patient Benefit Index (PAAPBI) scores at Visits 1 to 5. [ Time Frame: 48 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of LH-8 in Paediatric Alopecia Areata
• 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.

Brief Summary

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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Alopecia Areata
• Pediatric Disorder

Intervention

• Drug: LH-8
  LH-8 cutaneous solution
• Drug: Placebo
  Placebo cutaneous solution

Study Arms

• Experimental: LH-8 cutaneous solution
  LH-8 cutaneous solution (0.126 mL per spray) applied to the whole scalp:
  Intervention: Drug: LH-8
• Placebo Comparator: Placebo cutaneous solution
  Placebo cutaneous solution (0.126 mL per spray) applied to the whole scalp:
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 25, 2022): 107
• Original Estimated Enrollment (submitted: August 2, 2017): 100
• Actual Study Completion Date: September 14, 2022
• Actual Primary Completion Date: March 14, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Male and female children and adolescents aged 2 to less than 18 years with active alopecia areata involving 25% to 95% of the scalp between 6 months and 3 years in duration.

Diagnosis and main criteria for inclusion: Male and female children and adolescents aged 2 to less than 18 years with active alopecia areata involving 25% to 95% of the scalp between 6 months and 3 years in duration.

Inclusion criteria:

1. Male and female children and adolescents aged 2 to less than 18 years.
2. Active scalp alopecia areata, involving 25% to 95% of the scalp (as measured by SALT score at screening).
3. Duration of hair loss between 6 months and 3 years.
4. Female subjects of childbearing potential (postmenarcheal) must have a negative urine pregnancy test at screening. Females of childbearing potential must either not be sexually active or be using an adequate birth control method throughout the duration of the study.
5. All subjects taking thyroid medication or hormonal therapy must be on a stable dose for 6 months and maintain such throughout the study.
6. Subjects must be willing to maintain the same hair style, including hair dye, throughout the study period.
7. Written informed consent signed by parent(s) or legally authorized representative and assent or consent signed by the subjects, if applicable, according to national regulations prior to any protocol specific procedures.

Exclusion criteria:

1. Hypersensitivity or intolerance to any active IMP substances (onion, citrus, caffeine, theobromine) or excipients (glycerine, betaine or ethanol).
2. Any cause of hair loss other than alopecia areata.
3. Active scalp inflammation except alopecia areata.
4. Nevi, cutaneous or non-cutaneous lesions currently undiagnosed but suspicious for malignancy.
5. Female adolescents who are pregnant or who are nursing or plan pregnancy during the trial period.
6. Use of topical medication (listed in protocol Section 10.7.1) within 2 weeks prior to Visit 1.
7. Use of systemic alopecia areata therapies (e.g. prednisone, cyclosporine, methotrexate), including use of these medications for other indications, and intralesional corticosteroids within 1 month prior to Visit 1.
8. Administration of hydroxychloroquine or finasteride within two months prior to Visit 1.
9. Use of phototherapy, laser therapy or excimer laser therapy on the scalp within three months prior to Visit 1.
10. Use of infliximab within two months, adalimumab within three months, and ustekinumab within four months prior to Visit 1 or use of other TNF inhibitors and biologic agents within one month or five half-lives before Visit 1, whichever is longer.
11. Prior treatment with IMP.
12. Evidence or history of alcohol, medication or drug abuse.
13. History of systemic or cutaneous medical, or psychiatric disease which will put subject at risk or interfere with assessments.
14. Participation in any other clinical trial within 30 days prior to Visit 1.
15. Subject is in a dependent relationship (e.g. relative or family member) with the investigator's or sponsor's staff.
16. Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject's ability to comply with the study protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, France, Germany

Administrative Information

• NCT Number: NCT03240627
• Other Study ID Numbers: RAAINBOW
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Legacy Healthcare SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Legacy Healthcare SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Ulrike BLUME-PEYTAVI, Prof. Dr.; Charité-Universitätsmedizin Berlin, Dept Dermatology, Germany
• Principal Investigator: Pascal REYGAGNE, Dr.; Sabouraud Center, Saint-Louis Hospital, France
• Principal Investigator: Petyo Brezoev, Dr.; DDC Alexandrovska-Sofia", Bulgaria
• Study Director: Uwe Schwichtenberg, Dr.; Hautarztpraxis, Bremen-Vegesack, Germany
• Study Director: Maya Milanova, Dr; Center of Skin and venereal diseases, Sliven, Bulgaria
• Study Director: Mariyana Venelinova_Rusinova, Dr; MC Doverie, Sofia, Bulgaria
• Principal Investigator: Ishad Aggarwal, Dr; Health Point Hospital 21, Kolkata, India

• PRS Account: Legacy Healthcare SA
• Verification Date: June 2023