A Study of ATI-50002 Topical Solution for the Treatment of Alopecia Areata

Study Overview
=================
Brief Summary
-----------------
Primary: • To assess safety, tolerability and efficacy of 2 dose strengths of ATI-50002 Topical Solution, compared to vehicle in subjects with alopecia areata (AA) Secondary: • To evaluate key clinical outcome assessments

Detailed Description
-----------------
Primary: • To assess safety, tolerability and efficacy of 2 dose strengths of ATI-50002 Topical Solution, compared to vehicle in subjects with alopecia areata (AA) Secondary: • To evaluate key clinical outcome assessments

Official Title
-----------------
A Randomized, Double-Blind, Vehicle-Controlled Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of ATI-50002 Topical Solution Administered Twice-Daily for 6 Months in Adolescents and Adult Subjects With Stable Patchy Alopecia Areata With Optional Long-Term Open-Label Extension

Conditions
-----------------
Alopecia Areata

Intervention / Treatment
-----------------
* Drug: ATI-50002 high dose
* Drug: ATI-50002 low dose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a clinical diagnosis of stable patchy alopecia areata (AA) defined as no current areas of spontaneous regrowth. Have a Severity of Alopecia Tool (SALT) score of at least 15% up to 95% total scalp hair loss determined by the study investigator at baseline. Have a duration of the current episode of scalp hair loss of a minimum of 6 months and a maximum of 12 years. If a woman of childbearing potential (WOCBP), must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2) and agree to: use a highly effective method of birth control for the duration of the study; not be planning a pregnancy during the study duration and use contraception for 30 days after last application of study medication. Exclusion Criteria: Females who are nursing, pregnant, or planning to become pregnant for the duration of the study and up to 30 days after the last application of study medication. Diffuse alopecia areata. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia or scarring alopecia (e.g., cicatricial alopecia, frontal fibrosing alopecia, etc.). Active skin disease on the scalp (such as psoriasis or seborrheic dermatitis) or a history of skin disease on the scalp that in the opinion of the investigator would interfere with the study assessments of efficacy or safety. Active scalp trauma or other condition affecting the scalp that, in the investigator's opinion, may affect the course of AA or interfere with the study conduct or evaluations. The presence of a permanent or difficult to remove hairpiece or wig that will, in the opinion of the investigator, interfere with study assessments if not removed at each visit.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ATI-50002 high dose Topical Solution<br>High dose active | Drug: ATI-50002 high dose<br>* Topical solution<br>|
| Active Comparator: ATI-50002 low dose Topical Solution<br>low dose active | Drug: ATI-50002 low dose<br>* Topical solution<br>|
| Placebo Comparator: Vehicle Topical Solution<br>placebo | Drug: Placebo<br>* Topical solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Severity of Alopecia Tool Score at Week 24 | The Severity of Alopecia Tool (SALT) score is a physician administered scale measuring the amount of scalp without any terminal hair assessed by the investigator at Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24. Possible scores range from 0 (no scalp hair loss) to 100 (complete scalp hair loss). A negative change in the SALT score over time represents hair regrowth. The primary efficacy variable was the percent change from baseline in SALT score at Week 24. This was calculated as the mean of the changes from Baseline (Visit 2) SALT score to Week 24 (Visit 10) SALT score, divided by Baseline SALT score and expressed as a percentage. | Baseline - Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Alopecia Density and Extent Score at Week 24 | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator at Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24. ALODEX breaks the scalp up into a grid of 1% scalp surface areas and assigns density rating in each area on a 10 point scale of hair loss (0= no hair loss to 10 = complete baldness). Summation of scores from each 1% scalp surface area provides an overall score which may range from 0 (no scalp hair loss) to 100 (complete baldness). A negative change in the ALODEX score over time represents hair regrowth. | Baseline - Week 24 | 
| Mean Change From Baseline in Severity of Alopecia Tool Score at Week 24 | The Severity of Alopecia Tool (SALT) score is a physician administered scale measuring the amount of scalp without any terminal hair. Possible scores range from 0 (no scalp hair loss) to 100 (complete scalp hair loss). A negative change in the SALT score over time represents hair regrowth. | Baseline - Week 24 | 
| Mean Change From Baseline in Alopecia Density and Extent Score at Week 24 | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator at Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24. ALODEX breaks the scalp up into a grid of 1% scalp surface areas and assigns density rating in each area on a 10 point scale of hair loss (0= no hair loss to 10 = complete baldness). Summation of scores from each 1% scalp surface area provides an overall score which may range from 0 (no scalp hair loss) to 100 (complete baldness). A negative change in the ALODEX score over time represents hair regrowth. | Baseline - Week 24 | 
| Proportion of Subjects Achieving ≥50% Hair Regrowth Based on Severity of Alopecia Tool Scores at Week 24 | A summary of the proportion of subjects in each treatment arm achieving ≥50% hair regrowth compared with baseline using Severity of Alopecia Tool scores at Week 24 is presented. | Baseline - Week 24 | 
| Proportion of Subjects Achieving ≥50% Hair Regrowth Based on Alopecia Density and Extent Scores at Week 24 | A summary of the proportion of subjects in each treatment arm achieving ≥50% hair regrowth compared with baseline using Alopecia Density and Extent scores at Week 24 is presented. | Baseline - Week 24 | 
| Proportion of Subjects With ≥2 Point Improvement in Scalp Patient Reported Outcome for Target Patch at Week 24 | The Scalp Patient Reported Outcome for Target Patch assesses the appearance of the subject's target patch (identified by the subject as his or her most bothersome area of scalp hair loss at Baseline) and was completed by subjects at Baseline, Week 4, Week 12, and Week 24. The assessment has a recall period of right now and includes a five-point VRS ranging from Full hair, scalp of the target patch completely covered with hair to no hair, scalp of the target patch completely exposed. The instrument produces a score of 1 to 5, with lower scores indicating more hair covering the subject's target patch. A summary of the proportion of subjects with ≥2 point improvement in Subject Target Patch assessment at Week 24 compared to baseline is presented. | Baseline - Week 24 | 
| Proportion of Subjects With ≥1 Point Improvement in Scalp Patient Reported Outcome for Entire Scalp at Week 24 | The Scalp Patient Reported Outcome for Entire Scalp assesses the appearance of the subject's whole scalp and was completed by subjects at Baseline, Week 4, Week 12, and Week 24. The assessment has a recall period of right now and includes a five-point VRS ranging from Full hair, whole scalp completely covered with hair to no hair, whole scalp completely exposed. The instrument produces a score of 1 to 5, with lower scores indicating more hair covering the subject's target patch. A summary of the proportion of subjects with ≥1 point improvement in Subject Entire Scalp assessment at Week 24 compared to baseline is presented. | Baseline - Week 24 | 
| Proportion of Subjects With ≥2-Point Improvement in Scalp Clinician Reported Outcome for Target Patch at Week 24 | The Scalp Clinician Reported Outcome for Target Patch provides the investigator's assessment of the appearance of the subject's target patch (identified by the subject as his or her most bothersome area of scalp hair loss at Baseline) and was completed by investigators at Baseline, Week 4, Week 12, and Week 24. The assessment has a recall period of right now and includes a five-point VRS ranging from Full hair, scalp of the target patch completely covered with hair to no hair, scalp of the target patch completely exposed. The instrument produces a score of 1 to 5, with lower scores indicating more hair covering the subject's target patch. A summary of the proportion of subjects with ≥2 point improvement in Clinician Target Patch assessment at Week 24 compared to baseline is presented. | Baseline - Week 24 | 
| Change From Baseline in Scalp Clinician Reported Outcome for Entire Scalp at Week 24 | The Scalp Clinician Reported Outcome for Entire Scalp assesses the appearance of the subject's whole scalp and was completed by investigators at Baseline, Week 4, Week 12, and Week 24. The assessment has a recall period of right now and includes a five-point VRS ranging from Full hair, whole scalp completely covered with hair to no hair, whole scalp completely exposed. The instrument produces a score of 1 to 5, with lower scores indicating more hair covering the subject's target patch. Change status is categorized as 'Better by x points' when the score decreases from baseline by x points, and as 'Worse by x points' when the score increases by x points. | Baseline - Week 24 | 
| Change From Baseline in the Physician Global Impression of Severity (PhGIS) of Patchy Alopecia Areata at Week 24 | The Physician Global Impression of Severity (PhGIS) is a 5-point descriptive scale completed by investigators at Baseline, Week 4, Week 12, and Week 24 and is used to capture the investigator's assessment of the subject's disease severity at a particular timepoint. Scores of 1 to 5 are assigned to responses Mild to Extremely Severe, respectively. Change status is categorized as 'Better by x points' when the score decreases from baseline by x points, and as 'Worse by x points' when the score increases by x points. | Baseline - Week 24 | 
| Change From Baseline in the Subject Global Impression of Severity of Patchy Alopecia Areata at Week 24 | The Subject Global Impression of Severity (SGIS) is a 5-point descriptive scale completed by subjects at Baseline, Week 4, Week 12, and Week 24 and is used to capture the subject's assessment of disease severity at a particular timepoint. Scores of 1 to 5 are assigned to responses Mild to Extremely Severe, respectively. Change status is categorized as 'Better by x points' when the score decreases from baseline by x points, and as 'Worse by x points' when the score increases by x points. | Baseline - Week 24 | 
| Alopecia Impact Assessment Patient Reported Outcome Change From Baseline at Week 24 | The Alopecia Impact Assessment (AIA) is a 13-item patient reported outcome questionnaire which measures the subject's experience with impacts related to alopecia areata in managing appearance, worry, sadness, loss of confidence, self-consciousness, embarrassment, feeling unattractive, limitation of social activities, limitation of physical activities, unwanted attention, sweat in eyes, debris in eyes, and debris in nose. The AIA was completed by subjects at Baseline, Week 4, Week 12, and Week 24 and has a recall period of over the past seven days. An 11-point NRS with anchors 0 - Not at all [impact] and 10 - Extremely [impact] (e.g., Not at all bothersome and Extremely bothersome; Not at all worried and Extremely worried) is utilized. The AIA produces single-item (0-10) and mean total (0-10) scores, with higher scores indicating higher levels of impact. | Baseline - Week 24 | 
| Subject Global Impression of Treatment Satisfaction at Week 24 | The Subject Global Impression of Treatment Satisfaction (SGITS) is a 7-point descriptive scale completed by subjects at Week 12 and Week 24. Scale response options ranged from 1. Extremely Satisfied to 7. Extremely Dissatisfied and are used to capture how satisfied or dissatisfied they are with the study medication treatment received for their alopecia areata. | Week 24 | 
| Change in Dermatology Life Quality Index Total Score Between Baseline and Week 24 | The 10 question Dermatology Life Quality Index (DLQI) questionnaire was completed by subjects at Baseline, Week 4, Week 12, and Week 24. When completing the questionnaire, subjects were instructed to think of their hair loss in place of skin problem and skin as referenced in the questionnaire. Possible summary scores could range from 0 to 30 with higher scores indicating a worse outcome. | Baseline - Week 24 | 
| Physician Global Impression of Change at Week 24 | The Physician Global Impression of Change (PhGIC) is a 7-point descriptive scale completed by investigators at Week 24. Scale response options ranged from 1. Very much improved to 7. Very much worse and are used to capture the investigator's overall impression of change for the subject's alopecia during the treatment period. | Week 24 | 
| Subject Global Impression of Change at Week 24 | The Subject Global Impression of Change (SGIC) is a 7-point descriptive scale completed by subjects at Week 24. Scale response options ranged from 1. Very much improved to 7. Very much worse and are used to capture the subject's overall impression of change for his/her alopecia during the treatment period. | Week 24 |