Safety and Pharmacokinetic Study of ATI-50002 in Subjects With Alopecia Universalis (AU) and Alopecia Totalis (AT)

Study Overview
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Brief Summary
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The primary objective is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ATI-50002 Topical Solution compared to vehicle in subjects with AU and AT.

Detailed Description
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This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ATI-50002 Topical Solution in patients with Alopecia Universalis and Alopecia Totalis. Concentrations of ATI-50002 in the blood and skin will be assessed after 28 days of treatment with ATI-50002 Topical Solution.

Official Title
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A Randomized, Double-blind, Vehicle-controlled Multicenter Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of ATI-50002 Topical Solution Administered Twice-Daily for 28 Days in Adult Subjects With Alopecia Universalis and Alopecia Totalis With a 12-Month Long-Term Open-Label Extension

Conditions
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Alopecia Universalis (AU), Alopecia Totalis (AT)

Intervention / Treatment
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* Drug: Vehicle
* Drug: ATI-50002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and willing to sign an Informed Consent Form (ICF). Male or non-pregnant, non-nursing female ≥18 years old at the time of informed consent. Have a clinical diagnosis of stable, clinically typical, AU or AT. Have a duration of the current episode of AU or AT for a minimum of 6 months and a maximum of seven years. Be willing and able to follow all study instructions and to attend all study visits. Exclusion Criteria: Females who are nursing, pregnant, or planning to become pregnant for the duration of the study including 30 days after the last application of study medication. Patchy alopecia areata, diffuse alopecia areata or a history of an atypical pattern of Alopecia Areata (AA) (e.g., ophiasis, sisaihpo). 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 AU or AT 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle<br>Vehicle | Drug: Vehicle<br>* Vehicle Topical Solution<br>|
| Experimental: Active<br>ATI-50002 Topical Solution | Drug: ATI-50002<br>* ATI-50002 Topical Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double Blind Period: ATI-50002 Levels in Scalp Biopsy (ng/g) - Pharmacodynamic (PD) Population at Day 2 and Day 29 | ATI-50002 levels in scalp biopsies taken at Visits 3 (Day 2) and 7 (Day 29). | Day 2 - Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Open Label Extension: Mean Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 52 | 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 52 | 
| Open Label Extension: Mean Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 40 | 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 40 | 
| Open Label Extension: Mean Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 28 | 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 28 | 
| Open Label Extension: Change From Baseline in Alopecia Density and Extent Score (ALODEX) at Week 28 | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator. 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 28 | 
| Open Label Extension: Change From Baseline in Alopecia Density and Extent Score (ALODEX) at Week 40 | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator. 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 40 | 
| Open Label Extension: Change From Baseline in Alopecia Density and Extent Score (ALODEX) at Week 52 | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator. 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 52 | 
| Open Label Extension: Mean Change in Subject's Eyebrow Assessment (SEA) at Week 28 | The Subject Eyebrow Assessment (SEA) is the subject's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The SEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 28 | 
| Open Label Extension: Mean Change in Subject's Eyebrow Assessment (SEA) at Week 40 | The Subject Eyebrow Assessment (SEA) is the subject's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The SEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 40 | 
| Open Label Extension: Mean Change in Subject's Eyebrow Assessment (SEA) at Week 52 | The Subject Eyebrow Assessment (SEA) is the subject's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The SEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 52 | 
| Open Label Extension: Mean Change in Clinician's Eyebrow Assessment (CEA) at Week 28 | The Clinician's Eyebrow Assessment (CEA) is the investigator's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The CEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 28 | 
| Open Label Extension: Mean Change in Clinician's Eyebrow Assessment (CEA) at Week 40 | The Clinician's Eyebrow Assessment (CEA) is the investigator's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The CEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 40 | 
| Open Label Extension: Mean Change in Clinician's Eyebrow Assessment (CEA) at Week 52 | The Clinician's Eyebrow Assessment (CEA) is the investigator's assessment of the appearance of eyebrow hair present on the affected eyebrow(s) at a particular point in time. The CEA is a five-point VRS ranging from 0 - No eyebrow hair, 1 - A little eyebrow hair, 2 - Some eyebrow hair, 3 - Most eyebrow hair, and 4 - Full eyebrow hair with a recall period of right now. A positive change over time represents eyebrow regrowth (better outcome). | Week 4 - Week 52 | 
| Open Label Extension: Subject Global Impression of Treatment Satisfaction (SGIS) Week 28 | The Subject Global Impression of Treatment Satisfaction (SGIS) is a 7-point descriptive scale with a recall period of right now. The SGIS was completed by subjects during the Open Label period of the study. Scale response options ranged from 1: Extremely Satisfied, 2: Moderately Satisfied, 3: A little Satisfied, 4: Neither Satisfied or Dissatisfied, 5: A little Dissatisfied, 6: Moderately Dissatisfied, or 7: Extremely Dissatisfied and are used to capture how satisfied or dissatisfied subjects are with the study medication treatment received for their alopecia areata. | Week 28 | 
| Open Label Extension: Subject Global Impression of Treatment Satisfaction (SGIS) Week 40 | The Subject Global Impression of Treatment Satisfaction (SGIS) is a 7-point descriptive scale with a recall period of right now. The SGIS was completed by subjects during the Open Label period of the study. Scale response options ranged from 1: Extremely Satisfied, 2: Moderately Satisfied, 3: A little Satisfied, 4: Neither Satisfied or Dissatisfied, 5: A little Dissatisfied, 6: Moderately Dissatisfied, or 7: Extremely Dissatisfied and are used to capture how satisfied or dissatisfied subjects are with the study medication treatment received for their alopecia areata. | Week 40 | 
| Open Label Extension: Subject Global Impression of Treatment Satisfaction (SGIS) Week 52 | The Subject Global Impression of Treatment Satisfaction (SGIS) is a 7-point descriptive scale with a recall period of right now. The SGIS was completed by subjects during the Open Label period of the study. Scale response options ranged from 1: Extremely Satisfied, 2: Moderately Satisfied, 3: A little Satisfied, 4: Neither Satisfied or Dissatisfied, 5: A little Dissatisfied, 6: Moderately Dissatisfied, or 7: Extremely Dissatisfied and are used to capture how satisfied or dissatisfied subjects are with the study medication treatment received for their alopecia areata. | Week 52 | 
| Open Label Extension: Severity of Alopecia Tool (SALT) Scores, Relative Percent Regrowth (%) at Week 24 From Baseline | 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. A positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 24 | 
| Open Label Extension: Severity of Alopecia Tool (SALT Scores), Relative Percent Regrowth (%) at Week 40 From Baseline | 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. A positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 40 | 
| Open Label Extension: The Severity of Alopecia Tool (SALT) Scores, Relative Percent Regrowth (%) at Week 52 From Baseline | 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. A positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 52 | 
| Open Label Extension: The Alopecia Density and Extent (ALODEX) Scores, Relative Percent Regrowth (%) at 24 Weeks | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator. 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 positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 24 | 
| Open Label Extension: The Alopecia Density and Extent (ALODEX) Scores, Relative Percent Regrowth (%) at 40 Weeks | 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 positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 40 | 
| Open Label Extension: The Alopecia Density and Extent (ALODEX) Scores, Relative Percent Regrowth (%) at 52 Weeks | The Alopecia Density and Extent (ALODEX) score is a measurement of the amount of scalp with terminal hair loss assessed by the investigator. 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 positive percent change over time represents hair regrowth (better outcome). | Baseline - Week 52 |