Alopecia Areata, Alopecia Totalis, Alopecia Universalis
Conditions
Brief summary
This is an open label study of ATI-502 Topical Solution for the treatment of AA, AU, and AT with the following goals: * To assess the safety, tolerability, and efficacy of ATI-502 Topical Solution in subjects with AA, AU or AT following 24 weeks of treatment with ATI-501 Oral Suspension or Placebo Suspension. * To assess the ability of ATI-502 Topical Solution to maintain or improve hair regrowth in subjects previously treated with ATI-501 Oral Suspension or Placebo Suspension.
Detailed description
This Phase 2, multicenter, open-label study will evaluate the safety, tolerability, efficacy, and durability of efficacy of ATI-502 Topical Solution, 0.46% for the treatment of alopecia areata (AA), alopecia universalis (AU) and alopecia totalis (AT) in adult subjects who completed 24 weeks of treatment with ATI-501 Oral Suspension or Placebo Suspension. Subjects who complete 24 weeks of active treatment with ATI-501 Oral Suspension or Placebo Suspension in study ATI-501-AUAT-201 will be assessed for eligibility to enter the study. At Visit 9 in study ATI-501-AUAT-201, subjects who did not experience any adverse events (AEs), serious adverse events (SAEs), or tolerability issues that met study discontinuation criteria in study ATI-501-AUAT-201 and who in the opinion of the investigator are capable of re-growing or maintaining scalp hair and meet the entry criteria are eligible to enroll in this open-label study. Enrolled subjects will apply ATI-502 Topical Solution, 0.46% BID to the entire scalp and if applicable, the eyebrow(s) and return for safety and efficacy assessments as detailed in the Schedule of Assessments (Table 3). Assessment of response to treatment will be performed at Week 4, Week 8, Week 16, Week 24, and post-treatment Week 28. Safety and tolerability will be evaluated at each study visit by assessment of adverse events, clinical laboratory tests, and vital signs, and at Week 24, and physical examination findings
Interventions
DRUGATI 502 0.46% Topical Solution
apply ATI-502 Topical Solution, 0.46% Twice a day (BID) to the entire scalp and if applicable, the eyebrow(s)
Sponsors
Aclaris Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This Phase 2, multicenter, open-label study will evaluate the safety, tolerability, efficacy, and durability of efficacy of ATI-502 Topical Solution, 0.46% for the treatment of alopecia areata (AA), alopecia universalis (AU) and alopecia totalis (AT) in adult subjects who completed 24 weeks of treatment with ATI-501 Oral Suspension or Placebo Suspension.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet the following criteria to be eligible for participation in the study: 1. Subject must be able to comprehend and willing to sign the Informed Consent Form (ICF). 2. Male or non-pregnant, non-nursing female ≥ 18 years old at the time of informed consent. 3. Subject has completed 24 weeks of treatment and the assessments for Visit 9 in study ATI-501-AUAT-201. 4. Subject has not experienced any AEs, SAEs or tolerability issues that met study discontinuation criteria in ATI-501-AUAT-201. 5. Subject is capable of regrowing scalp hair or maintaining prior scalp hair regrowth from ATI-501-AUAT-201 in the opinion of the investigator. 6. If a woman of childbearing potential (WOCBP), must have a negative urine pregnancy test at Visit 1 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. (Refer to Section 8.4). 7. 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. 8. Be willing to maintain the same general hair style throughout the study period. Subjects who shave their scalp must be willing to refrain from shaving their scalp for at least one week or longer prior to each study visit, as determined by the investigator based on visible scalp hair growth. Hair trimming outside the treatment areas to maintain the current hair style is permitted. 9. Be willing and able to follow all study instructions and to attend all study visits. 10. Sexually active male subjects must agree to use a barrier method of contraception from the first application of study medication to at least 30 days after the last application of study medication.
Exclusion criteria
* Subjects are excluded from this study if any 1 or more of the following criteria is met: 1. Any study medication discontinuation criteria are met during participation in study ATI-501-AUAT-201. 2. 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. 3. 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. 4. Sensitivity to any of the ingredients in the study medications. 5. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least one week or longer prior to each study visit, as determined by the investigator based on visible scalp hair growth the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Severity of Alopecia Tool (SALT) Score | Baseline to 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. For the primary endpoint, the primary efficacy variable was the mean relative percent change from the original baseline visit in study ATI-501-AUAT-201 and the SALT score at Week 24 on study ATI-502-AA-203. This represents the percentage of hair regrowth. It was calculated as the mean of the changes from baseline SALT score to the SALT score at Week 24, divided by baseline SALT score and expressed as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Relative Percent Change From Baseline SALT Score | Baseline to Week 24 | Mean Relative Percent Change from Baseline (from the current study ATI-502-AA-203) in Severity of Alopecia Tool (SALT). SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss. A lower SALT score is a better outcome. A higher relative percent change is better. |
| Proportion of Subjects Achieving a SALT50 (Defined as a ≥ 50% Improvement From Baseline in SALT) by Visit | Baseline to Week 24 | Proportion of subjects achieving a SALT 50 (defined as a ≥ 50% improvement from baseline in SALT) by visit 6. SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss. |
| Proportion of Subjects Achieving a SALT 75 (Defined as a ≥ 75% Improvement From Baseline in SALT) by Visit | Baseline to Week 24 | Proportion of subjects achieving SALT 75 (defined as a ≥ 75% improvement from baseline in SALT) by visit 6 SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss. A bigger percent change is a more positive score. |
| Durability of Response | Baseline to Week 24 | Durability of response: Proportion of subjects achieving a SALT 50 or SALT 75 at Week 24 (in study ATI-501-AUAT-201) and maintaining that response at week 24 in ATI-502-AA-203 study. |
| Change From Baseline in the Physician Global Impression of Severity (PhGIS) | Baseline to Week 24 | Change from Baseline in the PhGIS by visit. The PhGIS is a 5 point scale from Mild to Extremely Severe. Mild is a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ATI 502 0.46% Topical Solution Subjects will apply ATI-502 Topical Solution, 0.46% twice-daily for 24 weeks followed by a 4-week post-treatment follow up period.
ATI 502 0.46% Topical Solution: apply ATI-502 Topical Solution, 0.46% Twice a day (BID) to the entire scalp and if applicable, the eyebrow(s) | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Study Terminated by Sponsor | 38 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | ATI 502 0.46% Topical Solution |
|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 14.36 |
| Duration of Alopecia (years) | 12.6 years STANDARD_DEVIATION 12.09 |
| Duration of Current Alopecia Episode (years) | 4.5 years STANDARD_DEVIATION 3.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Fitzpatrick Skin Type I - Always Burns | 2 Participants |
| Fitzpatrick Skin Type II - Burns Easily | 19 Participants |
| Fitzpatrick Skin Type III - Burns Moderately | 20 Participants |
| Fitzpatrick Skin Type IV - Burns Minimally | 6 Participants |
| Fitzpatrick Skin Type VI - Never Burns | 1 Participants |
| Fitzpatrick Skin Type V - Rarely Burns | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Region of Enrollment United States | 56 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 56 |
| other Total, other adverse events | 18 / 56 |
| serious Total, serious adverse events | 0 / 56 |
Outcome results
Primary
Change in the Severity of Alopecia Tool (SALT) Score
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. For the primary endpoint, the primary efficacy variable was the mean relative percent change from the original baseline visit in study ATI-501-AUAT-201 and the SALT score at Week 24 on study ATI-502-AA-203. This represents the percentage of hair regrowth. It was calculated as the mean of the changes from baseline SALT score to the SALT score at Week 24, divided by baseline SALT score and expressed as a percentage.
Time frame: Baseline to Week 24
Population: Only 8 of the 56 enrolled participants had efficacy measures on Day 169 (primary endpoint) of the ATI-502-AA-203 study. Based on this limited data set, the maintenance of, or new hair regrowth cannot be adequately assessed from this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATI 502 0.46% Topical Solution | Change in the Severity of Alopecia Tool (SALT) Score | -15.72 Percent Change from Baseline | Standard Deviation 35.383 |
Secondary
Change From Baseline in the Physician Global Impression of Severity (PhGIS)
Change from Baseline in the PhGIS by visit. The PhGIS is a 5 point scale from Mild to Extremely Severe. Mild is a better outcome.
Time frame: Baseline to Week 24
Population: Due to the premature termination of the study, the secondary efficacy endpoint analyses were not performed.
Secondary
Durability of Response
Durability of response: Proportion of subjects achieving a SALT 50 or SALT 75 at Week 24 (in study ATI-501-AUAT-201) and maintaining that response at week 24 in ATI-502-AA-203 study.
Time frame: Baseline to Week 24
Population: Due to the premature termination of the study, the secondary efficacy endpoint analyses were not performed.
Secondary
Mean Relative Percent Change From Baseline SALT Score
Mean Relative Percent Change from Baseline (from the current study ATI-502-AA-203) in Severity of Alopecia Tool (SALT). SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss. A lower SALT score is a better outcome. A higher relative percent change is better.
Time frame: Baseline to Week 24
Population: Due to the premature termination of the study, the secondary efficacy endpoint analyses were not performed.
Secondary
Proportion of Subjects Achieving a SALT50 (Defined as a ≥ 50% Improvement From Baseline in SALT) by Visit
Proportion of subjects achieving a SALT 50 (defined as a ≥ 50% improvement from baseline in SALT) by visit 6. SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss.
Time frame: Baseline to Week 24
Population: Due to the premature termination of the study, the secondary efficacy endpoint analyses were not performed.
Secondary
Proportion of Subjects Achieving a SALT 75 (Defined as a ≥ 75% Improvement From Baseline in SALT) by Visit
Proportion of subjects achieving SALT 75 (defined as a ≥ 75% improvement from baseline in SALT) by visit 6 SALT score is on a percent scale where 0% is no hair loss and 100 % is total hair loss. A bigger percent change is a more positive score.
Time frame: Baseline to Week 24
Population: Due to the premature termination of the study, the secondary efficacy endpoint analyses were not performed.