A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata (Up-AA)

• ClinicalTrials.gov Identifier: NCT06012240
• Recruitment Status: Recruiting
• First Posted: August 25, 2023
• Last Update Posted: May 10, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: August 22, 2023
• First Posted Date: August 25, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: October 11, 2023
• Estimated Primary Completion Date: May 26, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 22, 2023)

Percentage of Participants with the Achievement of Severity of Alopecia Tool (SALT) Score <= 20 [ Time Frame: 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%.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 23, 2024)

• Achievement of SALT score <= 20 for the Comparison of Upadacitinib Dose A QD Versus Placebo [ Time Frame: 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 Score <= 10 [ Time Frame: 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 Score <= 20 [ Time Frame: 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%.
• Percentage of Participants with the Achievement of Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss of 0 or 1 [ Time Frame: 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.
• Percentage of Participants with the Achievement of ClinRO Measure for Eyelash Hair Loss of 0 or 1 [ Time Frame: Baseline to Week 24 ]
  The ClinRO for Eyebrow 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 75 [ Time Frame: Baseline to Week 24 ]
  SALT 75 is defined as at least a 75% improvement [decrease] from Baseline in SALT score.
• Percentage of Participants with the Achievement of SALT 90 [ Time Frame: Baseline to Week 24 ]
  SALT 90 is defined as at least a 90% improvement [decrease] from Baseline in SALT score.
• Percent Change from Baseline in SALT Score [ Time Frame: 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 Patients' Global Impression of Change of Alopecia Areata (PaGIC-AA) Score of 1 "Much Better" or 2 "Moderately Better" [ Time Frame: 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."
• Percentage of Participants with the Achievement of Patient-Reported Outcome (PRO) for Scalp Hair Assessment 0/1 with ≥ 2-Point Improvement (Reduction) [ Time Frame: 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.
• Change from Baseline in Skindex-16 AA Emotions Domain Scores [ Time Frame: 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.
• Change from Baseline in Skindex-16 AA Functioning Domain Scores [ Time Frame: 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.
• Change from Baseline in Alopecia Areata Symptom Impact Scale (AASIS) Interference Subscale Score [ Time Frame: 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.
• Change from Baseline in AASIS Symptoms Subscale Score [ Time Frame: 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.
• 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 [ Time Frame: 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 0 [ Time Frame: 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%.

Original Secondary Outcome Measures (submitted: August 22, 2023)

• Percentage of Participants with the Achievement of SALT Score <= 10 [ Time Frame: 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 Score <= 20 [ Time Frame: 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%.
• Percentage of Participants with the Achievement of Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss of 0 or 1 [ Time Frame: 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.
• Percentage of Participants with the Achievement of ClinRO Measure for Eyelash Hair Loss of 0 or 1 [ Time Frame: Baseline to Week 24 ]
  The ClinRO for Eyebrow 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 75 [ Time Frame: Baseline to Week 24 ]
  SALT 75 is defined as at least a 75% improvement [decrease] from Baseline in SALT score.
• Percentage of Participants with the Achievement of SALT 90 [ Time Frame: Baseline to Week 24 ]
  SALT 90 is defined as at least a 90% improvement [decrease] from Baseline in SALT score.
• Percent Change from Baseline in SALT Score [ Time Frame: 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 Patients' Global Impression of Change of Alopecia Areata (PaGIC-AA) Score of 1 "Much Better" or 2 "Moderately Better" [ Time Frame: 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."
• Percentage of Participants with the Achievement of Patient-Reported Outcome (PRO) for Scalp Hair Assessment 0/1 with ≥ 2-Point Improvement (Reduction) [ Time Frame: 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.
• Percentage of Participants with the Achievement of SALT Score 0 [ Time Frame: 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%.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata
• Official Title: A Phase 3 Randomized, Placebo-controlled, Double-blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult and Adolescent Subjects With Severe Alopecia Areata

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 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 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 or Study 2, 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 240 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alopecia Areata

Intervention

• Drug: Upadacitinib
  Oral Tablets
  Other Names:

  • Rinvoq
  • ABT-494
• Drug: Placebo
  Oral Tablets

Study Arms

• Experimental: Study 1: Group 1 Upadacitinib Dose A
  Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.
  Intervention: Drug: Upadacitinib
• Experimental: Study 1: Group 2 Upadacitinib Dose B
  Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.
  Intervention: Drug: Upadacitinib
• Experimental: Study 1: Group 3 Placebo
  Participants will receive matching placebo once daily for 24 weeks in Period A.
  Intervention: Drug: Placebo
• Experimental: Study 1: Group 4 Upadacitinib Dose A
  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.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Placebo
• Experimental: Study 1: Group 5 Upadacitinib Dose B
  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.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Placebo
• Experimental: Study 1: Group 6 Placebo
  Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
  Intervention: Drug: Placebo
• Experimental: Study 2: Group 1 Upadacitinib Dose A
  Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.
  Intervention: Drug: Upadacitinib
• Experimental: Study 2: Group 2 Upadacitinib Dose B
  Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.
  Intervention: Drug: Upadacitinib
• Experimental: Study 2: Group 3 Placebo
  Participants will receive matching placebo once daily for 24 weeks in Period A.
  Intervention: Drug: Placebo
• Experimental: Study 2: Group 4 Upadacitinib Dose A
  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.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Placebo
• Experimental: Study 2: Group 5 Upadacitinib Dose B
  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.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Placebo
• Experimental: Study 2: Group 6 Placebo
  Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
  Intervention: Drug: Placebo
• Experimental: Study 3: Group 1 Upadacitinib Dose B (SALT > 20)
  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.
  Intervention: Drug: Upadacitinib
• Experimental: Study 3: Group 2 Upadacitinib Dose A (SALT ≤ 20)
  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.
  Intervention: Drug: Upadacitinib
• Experimental: Study 3: Group 3 Upadacitinib Dose B (Non-Sustained)
  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.
  Intervention: Drug: Upadacitinib
• Experimental: Study 3: Group 4 Upadacitinib Dose B (Sustained)
  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.
  Intervention: Drug: Upadacitinib
• Experimental: Study 3: Group 5 Upadacitinib Dose A (Sustained)
  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.
  Intervention: Drug: Upadacitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 22, 2023): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 3, 2028
• Estimated Primary Completion Date: May 26, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult individuals must be < 64 years old at Baseline Visit. Where permitted outside United States (OUS), adolescent individuals who are at least 12 years old at Screening may participate.
• 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 AND no significant scalp hair loss over the past 3 months.
• Current episode of AA of less than 8 years.

Exclusion Criteria:

• Diagnosis of primarily diffuse type of AA.
• 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, including but not limited to seborrheic dermatitis, scalp psoriasis, atopic dermatitis (AD), and tinea capitis.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 63 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Brazil, Canada, China, Japan, New Zealand, Puerto Rico, United Kingdom, United States

Administrative Information

• NCT Number: NCT06012240
• Other Study ID Numbers: M23-716; 2023-505061-82-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: May 2024