A Study To Assess Adverse Events and Effectiveness of Upadacitinib Oral Tablets in Adult and Adolescent Participants With 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 (NSV). Adverse effects and change in disease activity will be assessed. Upadacitinib is an approved drug for various immune-mediated inflammatory diseases and is currently being investigated for the treatment of NSV. There will be 2 replicate studies running at the same time. In Period A, participants are placed in 1 of 2 groups called treatment arms. Each group receives a different treatment. There is a 1 in 3 chance that participants will receive placebo and 2 in 3 chance participants will receive upadacitinib. In Period B, all participants will be in one treatment arm where they all receive upadacitinib. Approximately 270 adult and adolescent participants with NSV will be enrolled in each study (540 participants total) at approximately 90 sites worldwide. In Period A, participants will receive oral tablets of upadacitinib or placebo once a day for 48 weeks. In Period B, participants will receive oral tablets of upadacitinib 15 mg once a day for 112 weeks. Participants will be followed up for 30 days. 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 Phase 3, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, and Tolerability of Upadacitinib in Adult and Adolescent Subjects With Non-Segmental Vitiligo Who Are Eligible for Systemic Therapy

Conditions
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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: Documented clinical diagnosis of non-segmented vitiligo (NSV). At Screening and Baseline Visits, participants must satisfy at least 1 of the following criteria: >= 0.5 F-VASI and 5 <= T-VASI < 50 AND have failed at least 1 topical corticosteroid and/or at least 1 topical calcineurin inhibitor for vitiligo; or >= 0.5 F-VASI and 5 <= T-VASI < 50 AND have a sign of actively progressing vitiligo; or >= 0.5 F-VASI and 10 <= T-VASI < 50. Exclusion Criteria: Segmental or localized vitiligo. History of active skin disease other than vitiligo that could interfere with the assessment of vitiligo. >33% leukotrichia in areas of vitiligo on the face or > 33% leukotrichia in areas of vitiligo on the body (including the face).

Ages Eligible for Study
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Minimum Age: 12 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study 1, Period A: Group 1<br>Participants will receive upadacitinib 15 mg once a day for 48 weeks. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: Rinvoq;|
| Experimental: Study 2, Period A: Group 1<br>Participants will receive upadacitinib 15 mg once a day for 48 weeks. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: Rinvoq;|
| Placebo Comparator: Study 1, Period A: Group 2<br>Participants will receive placebo once daily for 48 weeks. | Drug: Placebo<br>* Oral Tablets<br>|
| Placebo Comparator: Study 2, Period A: Group 2<br>Participants will receive placebo once a day for 48 weeks. | Drug: Placebo<br>* Oral Tablets<br>|
| Experimental: Study 1, Period B: Extension Period<br>Participants will receive upadacitinib 15 mg once daily for 112 weeks. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: Rinvoq;|
| Experimental: Study 2, Period B: Extension Period<br>Participants will receive upadacitinib 15 mg once daily for 112 weeks. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: Rinvoq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 48 | 
| Percentage of Participants Achieving Facial-Vitiligo Area Scoring Index (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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 48 | 
| 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. | Week 24 | 
| Percent Change from Baseline in 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. | Week 24 | 
| 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. | Week 48 | 
| Percentage of Participants Achieving F-VASI 90 (≥ 90% 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. | Week 48 | 
| Percentage of Participants Achieving T-VASI 75 (≥ 75% 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. | Week 48 | 
| Percentage of Participants Achieving Patient Global Impression of Noticeability (PGIN) Score of Not Noticeable at All (0) or A Little Noticeable (1) For Participants with a Score of Moderately Noticeable (2) or Very Noticeable (3) at Baseline | The PGIN is a single item questionnaire to measure the participant's impression of noticeability of their depigmented vitiligo skin that uses a 4-point rating scale scored from 0 to 3 points: Not noticeable at all (score = 0); A little noticeable (score = 1); Moderately noticeable (score = 2); and Very noticeable (score = 3). Higher scores indicate worse outcomes. | Week 48 | 
| Percentage of Participants Achieving Patient Global Impression of Severity of Vitiligo Sun Sensitivity Score of Not Sensitive at All (0) or Mildly Sensitive (1) For Participants with a Score of Moderately Sensitive (2) or Higher at Baseline | The Patient Global Impression of Severity of Vitiligo Sun Sensitivity is a single item questionnaire that measures the participant's impression of sensitivity in their depigmented vitiligo skin in the sun. The measure uses a 5-point rating scale scored from 0 to 4 points: Not sensitive at all (score = 0); Mildly sensitive (score = 1); Moderately sensitive (score = 2); Severely sensitive (score = 3); and Very severely sensitive (score = 4). A score of 99 indicates the subject responded with I was not in the sun over the past week. Higher scores indicate worse outcomes. | Week 48 | 
| Percentage of Participants Achieving 3D Imaging Facial Vitiligo 40 (≥ 40% Reduction in Facial Vitiligo Area Measured by 3D Digital Imaging from Baseline) (Study 1 Only) | 3D imaging will be used to objectively quantify the facial vitiligo area. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitiligo, Non-Segmented Vitiligo, Viti-Up, Upadacitinib