ATI-501 Oral Suspension Compared to Placebo in Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis

Aclaris Therapeutics, Inc.87 enrolled

Overview

This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-501 for the treatment of Alopecia Areata (AA), Alopecia Universalis (AU) or Alopecia Totalis (AT) in adult subjects. Subjects will be required to have a clinical diagnosis of stable AA, AU, or AT. A total of approximately 80 subjects will be randomized.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Enrollment

Conditions

Alopecia

Interventions

ATI-501 400mg BID (Low dose)DRUG

ATI-501 400mg BID oral low dose for oral administration

ATI-501 600mg BID (Mid dose)DRUG

ATI-501 600mg BID oral mid dose for oral administration

ATI-501 800mg BID (High dose)DRUG

ATI-501 800mg BID high dose for oral administration

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Subjects must meet the following criteria to be eligible for participation in the study: 1. Able to comprehend and willing to sign an Informed Consent Form (ICF). 2. Male or non-pregnant, non-nursing female ≥ 18 years old at the time of informed consent. 3. Have a clinical diagnosis of stable Alopecia Areata (AA), Alopecia Universalis (AU), or Alopecia Totalis (AT). 4. If the subject is a woman of childbearing potential (WOCBP), she must have: * Negative urine and serum pregnancy tests at Screening (Visit 1); and * A negative urine pregnancy test at Baseline (Visit 2); and * Agree to not be planning a pregnancy during the study duration and use a highly effective method of contraception for the duration of the study and 30 days after the last dose of study medication. (Refer to Section 8.4.2). 5. Be in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of the subject or which might expose the subject to an unacceptable risk by study participation. 6. Be willing to maintain the same hair style and hair dyeing throughout the study period. 7. Subjects taking hormonal replacement therapies must be on stable doses for 6 months prior to enrollment and remain on a maintenance dose throughout the study. 8. Subjects taking thyroid replacement medication must be on stable doses for 6 months prior to enrollment and remain on a maintenance dose throughout the study. 9. Sexually active male subjects whose partner is a WOCBP must agree to use a barrier method of contraception from the first dose of study medication to at least 30 days after the last dose of study medication. Exclusion Criteria: Subjects are excluded from this study if any 1 or more of the following criteria is met: 1. Females who are nursing, pregnant, or planning to become pregnant for the duration of the study and up to 30 days after the last dose of study medication. 2. Diffuse AA or a history of an atypical pattern of AA. 3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia (AGA) or scarring alopecia. 4. Active skin disease on the scalp or a history of skin disease on the scalp that in the opinion of the investigator would interfere with study assessments of efficacy or safety. 5. Active scalp trauma or other condition affecting the scalp that, in the investigator's opinion, may affect the course of AA, AU or AT or interfere with the study conduct or evaluations. 6. 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. 7. History of, or current, severe, progressive or uncontrolled autoimmune, metabolic, hepatic, endocrine, renal, gastrointestinal, pulmonary, cardiovascular, genitourinary, or hematological disease, neurologic or cerebral disorders, or coagulation disorders that, as determined by the Investigator, would preclude participation in and completion of study assessments. 8. History of, current or suspected systemic or cutaneous malignancy and /or lymphoproliferative disease, other than subjects with a history of adequately treated and well healed and completely cleared non-melanoma skin cancers (e.g. basal or squamous cell carcinoma) treated successfully at least 1 year prior to study entry with no evidence of disease. 9. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the time of enrollment, or history of incompletely treated or untreated tuberculosis. Subjects who have completed therapy for latent tuberculosis may participate. 10. History of serious local infection (e.g., cellulitis, abscess) or systemic infection including but not limited to a history of treated infection (e.g., pneumonia, septicemia) within 3 months prior to Baseline. Subjects on an antibiotic for a nonserious, acute local infection must complete the course prior to enrollment into the study. 11. Positive for HIV, Hepatitis B or C. Subjects with serologic evidence of Hepatitis B vaccination (HepB surface Ab without the presence of Hep B surface Ag will be allowed to participate). 12. History of recurrent herpes zoster (more than one episode) or disseminated herpes zoster (a single episode) or disseminated herpes simplex (single episode) or cytomegalovirus (CMV) that resolved less than 2 months before study enrollment. Subjects with a history of frequent outbreaks of Herpes Simplex Virus (defined as 4 or more outbreaks a year). 13. Subjects who have received any of the following treatments for the timeframes specified below: * Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or immunosuppressants, including but not limited to: anakinra, adalimumab, azathioprine, corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF inhibitors, ustekinumab within 1 month or 5 half-lives (whichever is greater) of Baseline (Visit 2). * Plaquenil within 2 months of Baseline (Visit 2). * Janus kinase (JAK) inhibitors (oral or topical) within 6 months of Baseline (Visit 2). * Intralesional steroids or platelet rich plasma injections in the scalp within 1 month of Baseline (Visit 2). * Topical treatments on the scalp with anthralin, bimatoprost, corticosteroids, diphencyprone, diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE), minoxidil, pimecrolimus, or tacrolimus within 1 month of Baseline (Visit 2). * Phototherapy (narrow band Ultraviolet B \[NB UVB\] or broadband therapy) within 4 weeks of Baseline (Visit 2). 14. Participation in an investigational drug or device trial in which administration of an investigational drug or device occurred within 30 days or 5 half-lives (whichever is longer) of Baseline (Visit 2). 15. Any condition possibly affecting oral drug absorption, e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding are not exclusionary. 16. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least two weeks prior to a study visit, at the discretion of the investigator, based on the ability to assess hair growth. 17. Vaccination with a live or attenuated vaccine within 6 weeks prior to Baseline (Visit 2) or planned vaccination with these vaccines at any time during treatment or within 6 weeks following discontinuation of study medication.

Locations (25)

Aclaris Investigator Site

Hot Springs, Arkansas, United States

Outcomes

Primary Outcomes

Percent Change From Baseline in the Severity of Alopecia Tool (SALT) 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. 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 by adding the percentage hair loss in the various areas (i.e. top, back, each side) of the scalp. 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.

Time frame: Baseline-Week 24

Secondary Outcomes

Percent Change From Baseline in the Alopecia Density and Extent Score (ALODEX) 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.

Time frame: Baseline-Week 24

Mean Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24

Time frame: Baseline-Week 24

Data from ClinicalTrials.gov

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Placebo - oral administration

Aclaris Investigator Site

Rogers, Arkansas, United States

Aclaris Investigator Site

Denver, Colorado, United States

Aclaris Investigator Site

Boynton Beach, Florida, United States

Aclaris Investigator Site

Miami, Florida, United States

Aclaris Investigator Site

Sanford, Florida, United States

Aclaris Investigator Site

Snellville, Georgia, United States

Aclaris Investigator Site

Clinton Township, Michigan, United States

Aclaris Investigator Site

Detroit, Michigan, United States

Aclaris Investigator Site

Fridley, Minnesota, United States

...and 15 more locations

Mean Change From Baseline in the Alopecia Density and Extent (ALODEX) 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. 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.

Time frame: Baseline-Week 24

Count of Subjects Achieving at Least a 50% Reduction in Alopecia Density and Extent (ALODEX) Score at Week 24

Time frame: Baseline-Week 24

Count of Subjects in Each Treatment Arm Achieving at Least a 50% Reduction in Severity of Alopecia Tool (SALT) Score at Week 24 Compared to Baseline

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Left Eyebrow

The Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome is the investigator's assessment of the subject's facial hair (eyebrow(s), eyelashes,and if male, beard) at a particular point in time. The investigator was instructed to NOT refer to any other assessments to assist with these assessments. The investigator or designee assessed the affected facial hair areas (eyebrows, eyelashes and if male, beard) using a 5 point scale for each target area \[1-Full (Target Area Hair); 2-Most (Target Area Hair); 3-Some (Target Area Hair); 4-A Little (Target Area Hair); 5-No (Target Area Hair)\]. 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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Right Eyebrow

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Left Eyelash

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Right Eyelash

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Beard, Male Subjects

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Left Eyebrow

The Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome is the patient's assessment of their facial hair (eyebrow(s), eyelashes, and if male, beard) at a particular point in time. The patient assessed the affected facial hair areas (eyebrows, eyelashes and if male, beard) using a 5 point scale for each target area \[1-Full (Target Area Hair); 2-Most (Target Area Hair); 3-Some (Target Area Hair); 4-A Little (Target Area Hair); 5-No (Target Area Hair)\]. 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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Right Eyebrow

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Right Eyelash

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Left Eyelash

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Beard, Male Subjects

Time frame: Baseline-Week 24

Change From Baseline in the Subject Global Impression of Severity (SGIS) at Week 24, Patchy Alopecia Areata

The Subject Global Impression of Severity (SGIS) is a 5-point descriptive scale completed by subjects 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.

Time frame: Baseline-Week 24

Change From Baseline in the Subject Global Impression of Severity (SGIS) at Week 24, Alopecia Universalis or Alopecia Totalis

Time frame: Baseline-Week 24

Change From Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24, Patchy Alopecia Areata

The Physician Global Impression of Severity (PhGIS) is a 5-point descriptive scale completed by investigators 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.

Time frame: Baseline-Week 24

Change From Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24, Alopecia Universalis or Alopecia Totalis

Time frame: Baseline-Week 24

Alopecia Impact Assessment (AIA) 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 (inclusive of all 3 subtypes observed on study) 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 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.

Time frame: Baseline-Week 24

Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24, Patchy Alopecia Areata

The Subject Global Impression of Treatment Satisfaction (SGITS) is a 7-point descriptive scale completed by subjects. 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.

Time frame: Baseline-Week 24

Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24, Alopecia Universalis or Alopecia Totalis

Time frame: Baseline-Week 24

Change From Baseline in the Subject Global Satisfaction With Hair Quality (SGSHQ) for Entire Scalp at Week 24, Patchy Alopecia Areata

The investigator or study staff instructed the subject to answer the Subject Global Satisfaction with Hair Quality (SGSHQ) questionnaire in relation to their satisfaction with the quality of scalp hair at the time of questionnaire completion (ie "right now"). Subjects assessed their satisfaction with the quality of their scalp hair on a 7-point satisfaction scale from extremely satisfied to extremely dissatisfied at the visits. 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.

Time frame: Baseline-Week 24

Change From Baseline in the Subject Global Satisfaction With Hair Quality (SGSHQ) for Entire Scalp at Week 24, Alopecia Universalis or Alopecia Totalis

Time frame: Baseline-Week 24

Change in Dermatology Life Quality Index Total Score (DLQI) 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.

Time frame: Baseline-Week 24

Subject Global Impression of Change (SGIC) at Week 24

The Subject Global Impression of Change (SGIC) is a 7-point descriptive scale completed by subjects at Week 24 (Intent-to-treat population with reported data falling within the windowed Week 24 visit timeframe). 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.

Time frame: Baseline-Week 24

Physician Global Impression of Change (PhGIC) at Week 24

The Physician Global Impression of Change (PhGIC) is a 7-point descriptive scale completed by investigators at Week 24 (Intent-to-treat population with reported data falling within the windowed Week 24 visit timeframe). 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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Clinician Reported Outcome for Target Patch, Patchy Alopecia Areata

The Scalp Clinician Reported Outcome for Target Patch provides the investigator's assessment for Patchy Alopecia Areata (AAP) patients regarding the appearance of the patient's target patch (identified by the patient as his or her most bothersome area of scalp hair loss at Baseline). The assessment was completed by investigators at Baseline, Week 2, 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 patient'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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Clinician Reported Outcome for Entire Scalp, All Patients

The Scalp Clinician Reported Outcome for Entire Scalp was completed for patients with Patchy Alopecia Areata, Alopecia Universalis, and Alopecia Totalis and assesses the appearance of the patient's whole scalp. The assessment was completed by investigators at Baseline, Week 2, 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 patient's whole scalp. 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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Patient Reported Outcome for Target Patch, Patchy Alopecia Areata

The Scalp Patient Reported Outcome for Target Patch was completed by patients with Patchy Alopecia Areata (AAP) and 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). The assessment was completed by AAP subjects at Baseline, Week 2, 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. 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.

Time frame: Baseline-Week 24

Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Patient Reported Outcome for Entire Scalp, All Patients

The Scalp Patient Reported Outcome for Entire Scalp was completed by patients with Patchy Alopecia Areata, Alopecia Universalis, and Alopecia Totalis and assesses the appearance of the patient's whole scalp. The assessment was completed by patients at Baseline, Week 2, 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 patient'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.

Time frame: Baseline-Week 24