Treatment of Atopic Dermatitis and Alopecia Areata With Abrocitinib in Individuals With Down Syndrome

NCT ID: NCT07242638

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-05
• Study Completion Date: 2028-03-03

Brief Summary

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.

Detailed Description

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.

Conditions

Atopic Dermatitis; Alopecia Areata

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open Label Abrocitinib

Participants with DS with either AD or AA will be given Abrocitinib 100mg. In the case where patients is not responsive to treatment at Week 12 per protocol defined non-responder criteria, the treatment dosage will change to Abrocitinib 200 mg.

Group Type: EXPERIMENTAL

Abrocitinib

Intervention Type: DRUG

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.

Interventions

Abrocitinib

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria to be eligible as study participants:

• Male or female participants who are at least 12 years old, for whom signed informed consent can be provided by parent or legal guardian/LAR prior to participation in any study assessments or procedures.
• Diagnosis of Trisomy 21 or translocation Down Syndrome.
• Participant is able to adhere to the study visit schedule and other protocol requirements.
• Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Week 0/Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product (IP), FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: a. Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; or b. Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]).
• Participant is judged to be in otherwise good overall health following a detailed medical and medication history, physical examination, and laboratory testing.

Exclusion Criteria

Participants who meet any of the following criteria are not eligible for randomization as study participants:

• Inability or unwillingness of a participant's parent or legal guardian/LAR to give written informed consent or comply with study protocol.
• Participant is pregnant or breastfeeding.
• Participants with AA: A. cause of hair loss is indeterminable and/or they have concomitant causes of alopecia, such as traction, cicatricial, pregnancy-related, druginduced, telogen effluvium, or advanced androgenetic alopecia (i.e. Ludwig Type III or Norwood-Hamilton Stage ≥ V). B. Participant has a history of AA with no evidence of hair regrowth for ≥7 years since the last episode of hair loss
• Participant has increased risk of developing venous thromboembolism, e.g. deep vein thrombosis or pulmonary embolism (history of venous thromboembolism, or first-degree relative with unprovoked venous thromboembolism (i.e. without known underlying cause such as trauma, surgery, immobilization, prolonged travel, pregnancy, hormone use, or plaster cast), that would suggest participant is at increased risk of inherited coagulation disorder (e.g. Factor V Leiden).
• Participant currently has active forms of other inflammatory skin diseases (eg, psoriasis, seborrheic dermatitis, lupus) at the time of Day 1 that would interfere with evaluation of AD or AA.
• Participant was vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to Baseline visit, or is expected to be vaccinated or to have household exposure to these vaccines during treatment.
• Participant has a suspected or active lymphoproliferative disorder or malignancy; OR a history of malignancy within 5 years before the Week 0/Baseline assessment, except for completely treated in situ non-melanoma skin and cervical cancers without evidence of metastasis.
• Infection History: • Participant has an active bacterial, viral, or helminth parasitic infection; OR a history of ongoing, recurrent severe infections requiring systemic antibiotics. • Participant has active chronic or acute skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Baseline or superficial skin infections within 1 week prior to Baseline. • Participant has a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
• Participant has a history of alcohol or substance abuse within 6 months prior to Day 1 that in the opinion of the investigator will preclude participation in the study.
• Participant with a known or suspected underlying immunodeficiency or immune-compromised state as determined by the investigator.
• Participant has a concurrent or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, intestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease. ANY of the following abnormalities in renal or hepatic tests at screening are exclusionary: Estimated creatinine clearance <40 mL/min based on the age appropriate calculation, or serum creatinine >1.5 times the upper limit of normal (ULN); • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 times the ULN; • Total bilirubin ≥1.5 times the ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN.
• Participant has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) prior to Baseline.
• Participant has positive or indeterminable PPD or QFT result including participants that completed standard tuberculosis therapy prior to Baseline.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
• Participant has history of adverse systemic or allergic reactions to any component of the study drug or any safety event deemed "related" to a JAK inhibitor.
• Participant has used systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus, oral JAK inhibitor (tofacitinib, ruxolitinib, baricitinib, ritlecitinib, or investigational oral JAK Inhibitors) or ultraviolet (UV) phototherapy with/without Psoralen Ultraviolet A (PUVA) therapy, within 4 weeks prior to the Week 0/Baseline visit.
• Participant has used systemic monoclonal antibody treatments (such as the IL-4R antagonist dupilumab) within 12 weeks of Baseline visit.
• Participant has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus within 1 week prior to the Week 0/Baseline visit.
• Participant with Translocation or Mosaic Downs Syndrome.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Emma Guttman

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emma Guttman, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Dusan Bogunovic, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Giselle Singer

Role: CONTACT

giselle.singer@mssm.edu

212-241-3288

Facility Contacts

Giselle Singer

Role: primary

giselle.singer@mssm.edu

212-241-3288

Other Identifiers

1R61AR084210

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY-25-00773

Identifier Type: -

Identifier Source: org_study_id