Study to Evaluate Adverse Events and Change in Disease Activity With Oral Tablets of Upadacitinib in Adult Participants With Non-Segmental Vitiligo

Study Overview
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Brief Summary
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Vitiligo is a common chronic autoimmune disease that causes the body's immune system to attack its own pigment producing skin cells. This study is to evaluate how safe and effective upadacitinib is in participants with non-segmental vitiligo. Adverse effects and change in disease activity will be assessed. Upadacitinib is being evaluated for the treatment of non-segmental vitiligo. The study will enroll approximately 160 participants aged 18-65 with non-segmental vitiligo in 5 treatment arms across 35 sites worldwide. Participants will either receive study drug vs placebo oral tablets once daily (QD) for 24 weeks (Period A). In Period B (up to 52 weeks), participants who received placebo during the first 24 weeks will switch to study drug. Participants who received study drug during the first 24 weeks, will continue to receive study drug. 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.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Non-Segmental Vitiligo

Conditions
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Non-Segmental Vitiligo

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of non-segmental vitiligo (NSV) and no segmental or localized vitiligo. Participants with all of the following at Screening and Baseline. Visits: ≥ 0.5 F-VASI and ≥ 5 total vitiligo area scoring index (T-VASI). Participants who have had prior exposure to immunomodulatory biologic therapy, for any indications, but discontinued the biologic therapy prior to the first dose of study drug. Recommended washout periods for biologic therapies include ≥ 4 weeks for etanercept; ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and ixekizumab; ≥ 16 weeks for secukinumab; and ≥ 12 weeks for ustekinumab. For biologic therapies not specified, therapies must be discontinued at least 5 times the mean terminal elimination half-life of a drug or 3 months prior to Baseline, whichever is longer. Exclusion Criteria: Participants with segmental or localized vitiligo. Participants with other skin conditions that would interfere with evaluation of vitiligo, participants with uncontrolled thyroid disease, and participants with > 33% leukotrichia on the face or > 33% leukotrichia on the body (including face). Participants previously treated with any topical or systemic janus kinase (JAK) inhibitor or permanent skin bleaching agents. Participants treated with any systemic vitiligo therapy (e.g., methotrexate, mycophenolate mofetil, corticosteroids), supplemental vitiligo therapy (antioxidants/vitamins/herbal medicine/traditional Chinese medicine), and/or topical vitiligo therapy including permanent or temporary tattoos within a minimum of 30 days prior to the first dose of study drug (Note: Camouflage and makeup may be used). Participants treated with any phototherapy, including excimer (or other forms of laser therapy), within a minimum of 12 weeks prior to the first dose of study drug. Participants have history of malignancy other than successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery; History of an organ transplant which requires continued immunosuppression; History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment; Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded; Uncontrolled thyroid disease;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose A of Upadacitinib<br>Participants in this group will receive dose A of upadacitinib orally once daily (QD) for 52 weeks. | Drug: Upadacitinib<br>* Oral tablets<br>* Other names: RINVOQ;|
| Experimental: Dose B of Upadacitinib<br>Participants in this group will receive dose B of upadacitinib orally QD for 52 weeks. | Drug: Upadacitinib<br>* Oral tablets<br>* Other names: RINVOQ;|
| Experimental: Dose C of Upadacitinib<br>Participants in this group will receive dose C of upadacitinib orally QD for 52 weeks. | Drug: Upadacitinib<br>* Oral tablets<br>* Other names: RINVOQ;|
| Experimental: Placebo Followed by Dose A of Upadacitinib<br>Participants in this group will receive placebo for 24 weeks followed by dose A of upadacitinib orally QD for 28 weeks. | Drug: Upadacitinib<br>* Oral tablets<br>* Other names: RINVOQ;Drug: Placebo<br>* Oral tablets<br>|
| Experimental: Placebo Followed by Dose B of Upadacitinib<br>Participants in this group will receive placebo for 24 weeks followed by dose B of upadacitinib orally QD for 28 weeks. | Drug: Upadacitinib<br>* Oral tablets<br>* Other names: RINVOQ;Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3. | At 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3. | At 24 weeks | 
| Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3. | At 24 weeks | 
| Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area [BSA]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100. | At 24 weeks | 
| Percent Change From Baseline in T-VASI | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area [BSA]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100. | At 24 weeks | 
| Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score | The VitiQoL is a validated questionnaire used in clinical trials to assess stigma-related vitiligo impacts. The VitiQoL uses subject-elicited social, affective, and behavior items, asking the subject's appraisal of the vitiligo-related impacts over the last month. Fifteen items are scored on a 7-point scale ranging from 0 (Not at all) to 6 (All of the time). Item scores (0 to 6) are summed to provide a total score range of 0 to 90; higher scores indicate greater impairment of quality of life (QoL). | At 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitiligo, Non-segmental vitiligo (NSV), Upadacitinib, ABT-494, RINVOQ