Clinical trial NCT03594227: ATI-501 Oral Suspension Compared to Placebo in Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis
Official title: A Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of ATI-501 Oral Suspension Compared to Placebo in Adult Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alopecia
Lead sponsor: Aclaris Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-20
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24
timeFrame: Baseline-Week 24
Secondary outcomes:
measure: Percent Change From Baseline in the Alopecia Density and Extent Score (ALODEX) at Week 24
timeFrame: Baseline-Week 24
measure: Mean Change From Baseline in the Severity of Alopecia Tool (SALT) Score at Week 24
timeFrame: Baseline-Week 24
measure: Mean Change From Baseline in the Alopecia Density and Extent (ALODEX) Score at Week 24
timeFrame: Baseline-Week 24
measure: Count of Subjects Achieving at Least a 50% Reduction in Alopecia Density and Extent (ALODEX) Score at Week 24
timeFrame: Baseline-Week 24
measure: 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
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Left Eyebrow
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Right Eyebrow
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Left Eyelash
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Right Eyelash
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Clinician Reported Outcome, Beard, Male Subjects
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Left Eyebrow
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Right Eyebrow
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Right Eyelash
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Left Eyelash
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Facial Hair Appearance Assessment (AFHA)-Patient Reported Outcome, Beard, Male Subjects
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Subject Global Impression of Severity (SGIS) at Week 24, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Subject Global Impression of Severity (SGIS) at Week 24, Alopecia Universalis or Alopecia Totalis
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24, Alopecia Universalis or Alopecia Totalis
timeFrame: Baseline-Week 24
measure: Alopecia Impact Assessment (AIA) Patient Reported Outcome Change From Baseline at Week 24
timeFrame: Baseline-Week 24
measure: Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24, Alopecia Universalis or Alopecia Totalis
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Subject Global Satisfaction With Hair Quality (SGSHQ) for Entire Scalp at Week 24, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Change From Baseline in the Subject Global Satisfaction With Hair Quality (SGSHQ) for Entire Scalp at Week 24, Alopecia Universalis or Alopecia Totalis
timeFrame: Baseline-Week 24
measure: Change in Dermatology Life Quality Index Total Score (DLQI) Between Baseline and Week 24
timeFrame: Baseline-Week 24
measure: Subject Global Impression of Change (SGIC) at Week 24
timeFrame: Baseline-Week 24
measure: Physician Global Impression of Change (PhGIC) at Week 24
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Clinician Reported Outcome for Target Patch, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Clinician Reported Outcome for Entire Scalp, All Patients
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Patient Reported Outcome for Target Patch, Patchy Alopecia Areata
timeFrame: Baseline-Week 24
measure: Change From Baseline in Alopecia Scalp Appearance Assessment (ASAA): Scalp-Patient Reported Outcome for Entire Scalp, All Patients
timeFrame: Baseline-Week 24
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Aclaris Investigator Site
state: Arkansas
city: Rogers
country: United States
facility: Aclaris Investigator Site
state: Arkansas
city: Denver
country: United States
facility: Aclaris Investigator Site
state: Colorado
city: Boynton Beach
country: United States
facility: Aclaris Investigator Site
state: Florida
city: Miami
country: United States
facility: Aclaris Investigator Site
state: Florida
city: Sanford
country: United States
facility: Aclaris Investigator Site
state: Florida
city: Snellville
country: United States
facility: Aclaris Investigator Site
state: Georgia
city: Clinton Township
country: United States
facility: Aclaris Investigator Site
state: Michigan
city: Detroit
country: United States
facility: Aclaris Investigator Site
state: Michigan
city: Fridley
country: United States
facility: Aclaris Investigator Site
state: Minnesota
city: Minneapolis
country: United States
facility: Aclaris Investigator Site
state: Minnesota
city: Saint Joseph
country: United States
facility: Aclaris Investigator Site
state: Missouri
city: Omaha
country: United States
facility: Aclaris Investigator Site
state: Nebraska
city: Las Vegas
country: United States
facility: Aclaris Investigator Site
state: Nevada
city: New York
country: United States
facility: Aclaris Investigator Site
state: New York
city: Rochester
country: United States
facility: Aclaris Investigator Site
state: New York
city: Portland
country: United States
facility: Aclaris Investigator Site
state: Oregon
city: Greenville
country: United States
facility: Aclaris Investigator Site
state: South Carolina
city: Knoxville
country: United States
facility: Aclaris Investigator Site
state: Tennessee
city: Nashville
country: United States
facility: Aclaris Investigator Site
state: Tennessee
city: Austin
country: United States
facility: Aclaris Investigational Site
state: Texas
city: Houston
country: United States
facility: Aclaris Investigator Site
state: Texas
city: San Antonio
country: United States
facility: Aclaris Investigator Site
state: Texas
city: Lynchburg
country: United States
facility: Aclaris Investigator Site
state: Virginia
city: Norfolk
country: United States
facility: Aclaris Investigator Site
state: Virginia
Study officials:
affiliation: Aclaris Therapeutics
name: Susan Moran, RN
role: STUDY_CHAIR
References: