A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata
- Registration Number
- NCT06012240
- Lead Sponsor
- AbbVie
- Brief Summary
Alopecia areata (AA) is a disease that happens when the immune system attacks hair follicles and causes hair loss. AA usually affects the head and face, but hair loss can happen on any part of the body. The purpose of this study is to assess how safe, effective, and tolerable upadacitinib is in adolescent and adult participants with severe AA.
Upadacitinib is an approved drug being investigated for the treatment of AA. In Study 1 and Study 2 and Study 4 Period A, participants are placed in 1 of 3 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 5 chance that participants will be assigned to placebo. In Study 1 and Study 2 and Study 4 Period B, participants originally randomized to upadacitinib dose group in Period A will continue their same treatment in Period B. Participants originally randomized to Placebo in Period A will either remain on placebo in Period B, or be randomized in 1 of 2 groups, based off of their Severity of Alopecia Tool (SALT) score. Participants who complete Study 1, Study 2 or Study 4, can join Study 3 and may be re-randomized to receive 1 of 2 doses of upadacitinib for up to 108 weeks. Around 1500 participants with severe AA will be enrolled in the study at approximately 280 sites worldwide.
Participants will receive oral tablets of either upadacitinib or placebo once daily for up to 160 weeks with the potential of being re-randomized into a different treatment group at Weeks 24 and 52. Participants will be followed up for up to 30 days after last study drug dose.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1399
- Adult individuals must be < 64 years old at Baseline Visit. Where permitted outside United States (US)/European Union (EU), adolescent individuals who are at least 12 years old at Screening may participate in Study 1 and Study 2. Adolescent individuals in the US who are at least 12 years old at Screening may participate in Study 4.
- Diagnosis of severe alopecia areata (AA) with Severity of Alopecia Tool (SALT) score >= 50 scalp hair loss at Screening and Baseline.
- Severe AA with no spontaneous scalp hair regrowth over the past 6 months.
- Current episode of AA of less than 8 years.
- Current diagnosis of primarily diffuse type of AA.
- Current diagnosis of other types of alopecia that would interfere with evaluation of AA, including but not limited to female pattern hair loss, male pattern hair loss (androgenetic alopecia) Stage III or greater based on Hamilton-Norwood classification, traction alopecia, lichen planopilaris (LPP), discoid lupus, frontal fibrosing alopecia (FFA), central centrifugal cicatricial alopecia (CCCA), folliculitis decalvans, trichotillomania, and telogen effluvium.
- Diagnosis of other types of inflammatory scalp, eyebrow, or eyelash disorders that would interfere with evaluation of AA as determined by the investigator, including but not limited to seborrheic dermatitis, scalp psoriasis, atopic dermatitis (AD), and tinea capitis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Study 1: Group 1 Upadacitinib Dose A Upadacitinib Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B. Study 1: Group 2 Upadacitinib Dose B Upadacitinib Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B. Study 1: Group 3 Placebo Placebo Participants will receive matching placebo once daily for 24 weeks in Period A. Study 1: Group 4 Upadacitinib Dose A Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B. Study 1: Group 4 Upadacitinib Dose A Placebo Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B. Study 1: Group 5 Upadacitinib Dose B Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B. Study 1: Group 5 Upadacitinib Dose B Placebo Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B. Study 1: Group 6 Placebo Placebo Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160. Study 2: Group 1 Upadacitinib Dose A Upadacitinib Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B. Study 2: Group 2 Upadacitinib Dose B Upadacitinib Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B. Study 2: Group 3 Placebo Placebo Participants will receive matching placebo once daily for 24 weeks in Period A. Study 2: Group 4 Upadacitinib Dose A Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B. Study 2: Group 4 Upadacitinib Dose A Placebo Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B. Study 2: Group 5 Upadacitinib Dose B Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B. Study 2: Group 5 Upadacitinib Dose B Placebo Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B. Study 2: Group 6 Placebo Placebo Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160. Study 3: Group 1 Upadacitinib Dose B (SALT > 20) Upadacitinib Participants receiving upadacitinib Dose A with a SALT score \> 20 at Week 52 (end of Period B) of Study 1 or Study 2 will dose escalate to upadacitinib Dose B once daily for 108 weeks. Study 3: Group 2 Upadacitinib Dose A (SALT ≤ 20) Upadacitinib Participants receiving upadacitinib Dose A with a SALT score ≤ 20 at Week 52 (end of Period B) of Study 1 or Study 2 will remain on upadacitinib Dose A once daily for 108 weeks. Study 3: Group 3 Upadacitinib Dose B (Non-Sustained) Upadacitinib Participants who end Period B on upadacitinib Dose B with a with a SALT score \> 20 at Week 40 or Week 52 of Study 1 or Study 2 will remain on upadacitinib Dose B once daily for 108 weeks. Study 3: Group 4 Upadacitinib Dose B (Sustained) Upadacitinib Participants who end Period B on upadacitinib Dose B with a with a SALT score ≤ 20 at Week 40 and Week 52 of Study 1 or Study 2 will be re-randomized to receive upadacitinib Dose B once daily for 108 weeks. Study 3: Group 5 Upadacitinib Dose A (Sustained) Upadacitinib Participants who end Period B on upadacitinib Dose B with a with a SALT score ≤ 20 at Week 40 and Week 52 of Study 1 or Study 2 will be re-randomized to receive upadacitinib Dose A once daily for 108 weeks. Study 4: Group 1 Upadacitinib Dose A Upadacitinib US only adolescent participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B. Study 4: Group 2 Upadacitinib Dose B Upadacitinib US only adolescent participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B. Study 4: Group 3 Placebo Placebo US only adolescent participants will receive matching placebo once daily for 24 weeks in Period A. Study 4: Group 4 Upadacitinib Dose A Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B. Study 4: Group 5 Upadacitinib Dose B Upadacitinib Participants initially randomized to placebo (Period A) with a SALT score \> 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B. Study 4: Group 6 Placebo Placebo Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) Up to approximately 164 weeks An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Percentage of Participants with the Achievement of Severity of Alopecia Tool (SALT) Score <= 20 Week 24 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
- Secondary Outcome Measures
Name Time Method Achievement of SALT score <= 20 for the Comparison of Upadacitinib Dose A QD Versus Placebo Week 24 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
Percentage of Participants with the Achievement of Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss of 0 or 1 Baseline to Week 24 The ClinRO for Eyebrow Hair Loss is a 4-point response scale where 0 = The eyebrows have full coverage and no areas of hair loss and 3 = No notable eyebrows. Responses should have a ≥ 2-point improvement from Baseline among participants with Baseline score ≥ 2.
Percent Change from Baseline in SALT Score Baseline to Week 24 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
Percentage of Participants with the Achievement of Patient-Reported Outcome (PRO) for Scalp Hair Assessment 0/1 with ≥ 2-Point Improvement (Reduction) Baseline to Week 24 The PRO for Scalp Hair Assessment is single item, five-point, categorical response scale that asks respondents to look in the mirror and assess the total area of the scalp with missing hair. Response items range from "No missing hair" to "Nearly all or all" and includes percentage ranges for each category (0%, 1 to 20%, 21 to 49%, 50 to 94%, and 95 to 100%). Responses among participants with baseline score \>=3.
Achievement of Hospital Anxiety and Depression Scale (HADS)-Anxiety < 8 and HADS-Depression < 8 at Week 24 Among Participants with HADS-A >= 8 or HADS-D >= 8 at Baseline Baseline to Week 24 The HADS is a self-administered scale which measures anxiety and depression. It contains 14 items and is comprised of anxiety (7 items) and depression (7 items) subscales, which are scored separately and summed to give a total score. Item scores range from 0 (best) to 3 (worst), and total scores are categorized as normal (0 to 7), borderline abnormal (8 to 10), and abnormal (11 to 21).
Percentage of Participants with the Achievement of SALT Score <= 10 Up to Week 24 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
Percentage of Participants with the Achievement of ClinRO Measure for Eyelash Hair Loss of 0 or 1 Baseline to Week 24 The ClinRO for Eyelash Hair Loss is a 4-point response scale where 0 = The eyelashes form a continuous line along the eyelids on both eyes and 3 = No notable eyelashes. Responses should have a ≥ 2-point improvement from Baseline among participants with Baseline score ≥ 2.
Percentage of Participants with the Achievement of SALT Score 0 Week 24 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
Percentage of Participants with the Achievement of SALT 90 Baseline to Week 24 SALT 90 is defined as at least a 90% improvement \[decrease\] from Baseline in SALT score.
Percentage of Participants with the Achievement of Patients' Global Impression of Change of Alopecia Areata (PaGIC-AA) Score of 1 "Much Better" or 2 "Moderately Better" Up to Week 24 The PaGIC-AA is a single-item measure that asks participants to rate how their alopecia condition has changed overall since the start of the study using a 7-point scale. Responses range from "much better" to "much worse."
Change from Baseline in Alopecia Areata Symptom Impact Scale (AASIS) Interference Subscale Score Week 24 The AASIS Interference Subscale is a 6-item assessment with scores ranging from 0 = 'did not interfere' to 10 = 'interfered completely' with higher scores indicating greater symptom interference.
Percentage of Participants with the Achievement of SALT Score <= 20 Up to Week 12 The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
Change from Baseline in Skindex-16 AA Emotions Domain Scores Week 24 The Skindex-16 AA Emotions Domain is a 7-item assessment ranging from 0 = never bothered to 6 = always bothered that measures the effects of AA on a subject's health-related quality of life. Higher scores indicate greater impact on health-related quality of life.
Percentage of Participants with the Achievement of SALT 75 Baseline to Week 24 SALT 75 is defined as at least a 75% improvement \[decrease\] from Baseline in SALT score.
Change from Baseline in AASIS Symptoms Subscale Score Week 24 The AASIS Symptom Subscale is a 7-item assessment with scores ranging from 0 = 'not present' to 10 = 'as bad as you can imagine' with higher scores indicating greater symptom severity.
Change from Baseline in Skindex-16 AA Functioning Domain Scores Week 24 The Skindex-16 AA Emotions Domain is a 5-item assessment ranging from 0 = never bothered to 6 = always bothered, that measures the effects of AA on a subject's health-related quality of life. Higher scores indicate greater impact on health-related quality of life.
Trial Locations
- Locations (267)
Total Skin and Beauty Dermatology Center /ID# 259539
🇺🇸Birmingham, Alabama, United States
Duplicate_Advanced Research Associates - Glendale /ID# 259108
🇺🇸Glendale, Arizona, United States
Southwest Skin Specialists /ID# 258234
🇺🇸Phoenix, Arizona, United States
Alliance Dermatology and Mohs Center /ID# 258111
🇺🇸Phoenix, Arizona, United States
Johnson Dermatology Clinic /ID# 259103
🇺🇸Fort Smith, Arkansas, United States
Duplicate_JOSEPH RAOOF MD,INC /ID# 258031
🇺🇸Encino, California, United States
First OC Dermatology /ID# 259220
🇺🇸Fountain Valley, California, United States
University of California Irvine /ID# 259096
🇺🇸Irvine, California, United States
Dermatology Research Associates /ID# 258033
🇺🇸Los Angeles, California, United States
Stanford University School of Medicine - Redwood City /ID# 259542
🇺🇸Redwood City, California, United States
Scroll for more (257 remaining)Total Skin and Beauty Dermatology Center /ID# 259539🇺🇸Birmingham, Alabama, United States