This is a single-center, open-label, basket phase 2b trial that will enroll Down Syndrome (DS) participants with at least one inflammatory skin condition (Atopic Dermatitis (AD) and/or Alopecia Areata (AA)). Patients will receive Abrocitinib 100 mg daily for 12 weeks. Responders (defined as achieving Eczema Area and Severity Index (EASI) 75 response for AD, or SALT \<= 20 for AA) will be kept on this dose, and non-responders based on these definitions, will initiate 200 mg daily for another 12 weeks. All AD and AA patients will be maintained on the respective dose of Abrocitinib from Week 24 through week 60.
This is a single-center, open-label, basket phase 2b trial that will enroll DS subjects with at least one inflammatory skin condition (Atopic Dermatitis \[AD\] and/or Alopecia Areata \[AA\]). As our goal is to have 51 patients complete the study, with an estimated dropout rate of \~10%, we will enroll a total of n=56 patients. Patients will receive abrocitinib 100 mg daily for 12 weeks. Responders (defined as achieving EASI75 response for AD, or SALT ≤20 for AA) will be kept on this dose, and non-responders based on these definitions, will initiate 200 mg daily for another 12 weeks. All AD and AA patients will be maintained on their respective dose of abrocitinib from Week 24 through week 60. Patients with AD and AA will have clinical evaluations as well as skin and blood specimens collected for molecular analysis at multiple time points. For AD patients, lesional and non-lesional tape strips will be collected at weeks 0, 12, 24, 48 and 60, and processed as we previously published. For AA patients, optional 2mm biopsies will be collected from lesional and non-lesional scalp at baseline and from lesional scalp at weeks 24 and 48. Blood samples (a total of 17mL at each visit, with 12mL dedicated to mechanistic analyses), will be collected at weeks 0, 12, 24, 36, 48, and 60.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
All participants will be started on 100mg Abrocitinib daily. Based on clinical response, non-responders will be increased to 200mg daily at week 12. Responders will continue to receive 100 mg dose of Abrocitinib. All AA and AD participants will be maintained on their dose of Abrocitinib through week 60.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGRate of Serious Adverse Events (SAEs) at Week 24 and Week 60
Rate of Serious Adverse Events (SAEs) at week 24 and at 60 weeks to assesses the clinical safety of Abrocitinib in patients with DS and AD or AA.
Time frame: Week 24 and Week 60
Number and Severity of SAEs and TEAEs at Weeks 4, 8, 12
Overall number and severity of SAEs and Treatment-Emergent Adverse Events (TEAEs) at weeks 4, 8, and 12.
Time frame: Weeks 4, 8, 12
Number of SAEs and TEAEs
Number and severity of SAEs and Treatment-Emergent Adverse Events (TEAEs) at weeks 16, 28, 36, 48 and 60 in each dose group
Time frame: Weeks 16, 28, 36, 48, 60
Proportion of Participants with AD Reaching EASI 75
The proportion of subjects with AD achieving EASI 75 at week 24. The proportion of patients who achieve an improvement of 75% or greater at week 24. The EASI index assigns proportionate values to 4 body regions. Each region is assigned a score of 0 to 3, indicating none, mild, moderate, and severe clinical expression. The percentage of area involved is also assigned an eruption proportional score from 0 to 6. The total body score for each body region is obtained by multiplying the sum of the severity scores by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gives the EASI total from 0-72, with higher score indicating more severity.
Time frame: Week 24
Proportion of Participants with AA reaching SALT ≤ 20
The proportion of subjects with AA achieving SALT ≤ 20 at week 24. SALT ≤ 20 is defined as the proportion of patients achieving ≤ 20% reduction in SALT score compared to baseline. Scalp is divided into 4 areas namely, Vertex - 40% (0.4) of scalp surface area; right profile of scalp - 18% (0.18) of scalp surface area; left profile of scalp - 18% (0.18) of scalp surface area; Posterior aspect of scalp - 24% (0.24) of scalp surface area. Percentage of hair loss in any of these areas is percentage hair loss multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all above mentioned areas.
Time frame: Week 24
Change in proportions of participants with AD from baseline to Week 60
Change in proportions of patients achieving EASI 75 in participants with AD from baseline to week 60. The change in proportion of patients who achieve an improvement of 75% or greater from their Baseline EASI score to week 60. The EASI index assigns proportionate values to 4 body regions. Each region is assigned a score of 0 to 3, indicating none, mild, moderate, and severe clinical expression. The percentage of area involved is also assigned an eruption proportional score from 0 to 6. The total body score for each body region is obtained by multiplying the sum of the severity scores by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gives the EASI total from 0-72, with higher score indicating more severity.
Time frame: Baseline to Week 60
Change in Proportion of AA participants with SALT <=20 at Week 60
Change in proportion of AA patients with SALT ≤20 at week 60 compared to baseline in each treatment and dose group. SALT ≤ 20 is defined as the proportion of patients achieving ≤ 20% reduction in SALT score compared to baseline. Scalp is divided into 4 areas namely, Vertex - 40% (0.4) of scalp surface area; right profile of scalp - 18% (0.18) of scalp surface area; left profile of scalp - 18% (0.18) of scalp surface area; Posterior aspect of scalp - 24% (0.24) of scalp surface area. Percentage of hair loss in any of these areas is percentage hair loss multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all above mentioned areas.
Time frame: Baseline and Week 60
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.