A Study of INCB018424 Phosphate Cream in Subjects With Vitiligo

Study Overview
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Brief Summary
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The purpose of this study will be to examine the efficacy, safety, and tolerability of ruxolitinib cream in subjects with vitiligo.

Official Title
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A Randomized, Double-Blind, Dose-Ranging Study of INCB018424 Phosphate Cream in Subjects With Vitiligo

Conditions
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Vitiligo

Intervention / Treatment
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* Drug: Ruxolitinib cream
* Drug: Vehicle cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of vitiligo. Vitiligo with depigmented areas including: at least 0.5% of the total body surface area (BSA) on the face (0.5% BSA is approximately equal to the area of the participant's palm [without digits]) AND at least 3% of the total BSA on nonfacial areas (3% BSA is approximately equal to the area of 3 of the participant's handprints [palm plus 5 digits]). Participants who agree to discontinue all agents used to treat vitiligo from screening through the final follow-up visit. Over-the-counter preparations deemed acceptable by the investigator and camouflage makeups are permitted. Exclusion Criteria: Conditions at baseline that would interfere with evaluation of vitiligo. Participants who are receiving any kind of phototherapy, including tanning beds. Participants with other dermatologic disease besides vitiligo whose presence or treatments could complicate the assessment of repigmentation. Participants who have used skin bleaching treatments for past treatment of vitiligo or other pigmented areas. Participants who have received any of the following treatments within the minimum specified timeframes. Use of any biologic, investigational, or experimental therapy or procedure for vitiligo within 12 weeks or 5 half-lives (whichever is longer) of screening. Use of laser or light-based vitiligo treatments, including tanning beds, within 8 weeks of screening. Use of immunomodulating oral or systemic medications (eg, corticosteroids, methotrexate, cyclosporine) or topical treatments that may affect vitiligo (eg, corticosteroids, tacrolimus/pimecrolimus, retinoids) within 4 weeks of screening. Use of any prior and concomitant therapy not listed above that may interfere with the objective of the study as per discretion of the investigator, including drugs that cause photosensitivity or skin pigmentation (eg, antibiotics such as tetracyclines, antifungals) within 8 weeks of screening. Participants with a clinically significant abnormal thyroid-stimulating hormone or free T4 at screening. Participants with protocol-defined cytopenias at screening Participants with severely impaired liver function. Participants with impaired renal function. Participants taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 half-lives, whichever is longer, before the baseline visit. Participants who have previously received JAK inhibitor therapy, systemic or topical.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib cream 1.5% twice daily (BID)<br>Ruxolitinib cream 1.5% BID for 52 weeks, followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;|
| Experimental: Ruxolitinib cream 1.5% once daily (QD)<br>Ruxolitinib cream 1.5% QD in the morning (vehicle cream in the evening) for 52 weeks, followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;Drug: Vehicle cream<br>* Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.<br>|
| Experimental: Ruxolitinib cream 0.5% QD<br>Ruxolitinib cream 0.5% QD in the morning (vehicle cream in the evening) for 52 weeks, followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;Drug: Vehicle cream<br>* Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.<br>|
| Experimental: Ruxolitinib cream 0.15% QD<br>Ruxolitinib cream 0.15% QD in the morning (vehicle cream in the evening) for 52 weeks (opportunity for re-randomization to a higher dose at Week 24 if < 25% improvement in F-VASI score), followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;Drug: Vehicle cream<br>* Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.<br>|
| Placebo Comparator: Vehicle BID<br>Vehicle cream BID for 24 weeks, followed by re-randomization to ruxolitinib cream 1.5% BID, 1.5% QD, or 0.5% QD for Weeks 24 to 52, followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;Drug: Vehicle cream<br>* Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Treated With Ruxolitinib Cream Who Achieved a ≥ 50% Improvement From Baseline in Facial Assessment of the Vitiligo Area and Severity Index Score (F-VASI50) Compared With Participants Treated With Vehicle at Week 24 | An F-VASI50 responder achieved at least 50% improvement from Baseline in F-VASI, measured by the percentage of vitiligo involvement (percentage of body surface area [BSA]) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). | Baseline; Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Facial Assessment of the Physician's Global Vitiligo Assessment (F-PhGVA) of Clear or Almost Clear | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. | Week 24 | 
| Percentage of Participants Who Achieved a ≥ 50% Improvement From Baseline in Full Body Assessment of Vitiligo Area and Severity Index (T-VASI) at Week 52 | T-VASI was measured by the percentage of vitiligo involvement from all body regions (percentage of BSA; assessed by the Investigator) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was derived by multiplying the vitiligo involvement values by the percentage of affected skin for each body site and summing all values (possible range: 0-100; lower scores indicate increased improvement). | Baseline; Week 52 | 
| Dose Response on Percentage Change From Baseline in F-VASI |  | up to 156 weeks | 
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Grade 3 or Higher TEAE up to Week 24 | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was an AE reported for the first time or the worsening of a pre-existing event after first application of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. | up to 24 weeks | 
| Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE up to Week 52 | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was an AE reported for the first time or the worsening of a pre-existing event after first application of study drug. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. | up to 52 weeks | 
| Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE From Week 24 to Week 52 | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was an AE reported for the first time or the worsening of a pre-existing event after first application of study drug. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. | Week 24 to Week 52 | 
| Number of Participants Who Applied Ruxolitinib 1.5% Cream BID Throughout Study Participation With Any TEAE and Any Grade 3 or Higher TEAE | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was an AE reported for the first time or the worsening of a pre-existing event after first application of study drug. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. | up to Week 156 | 
| Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE From Week 52 to Week 156 | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was an AE reported for the first time or the worsening of a pre-existing event after first application of study drug. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. | Week 52 to Week 156 | 
| Mean Change From Baseline in F-VASI Score at Week 24 | F-VASI was measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; Week 24 | 
| Mean Change From Baseline in F-VASI Score at Weeks 52, 104, and 156 | F-VASI was measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; Weeks 52, 104, and 156 | 
| Percentage Change From Baseline in F-VASI Score at Week 24 | F-VASI was measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in F-VASI Score at Weeks 52, 104, and 156 | F-VASI was measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Weeks 52, 104, and 156 | 
| Percentage of Participants Who Achieved an F-VASI50 at Weeks 52, 104, and 156 | An F-VASI50 responder achieved at least 50% improvement from Baseline in F-VASI, measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). | Baseline; Weeks 52, 104, and 156 | 
| Percentage Change From Baseline in F-BSA Repigmentation at Week 24 | F-BSA involvement was the proportion of the facial body surface area with vitiligo. The area Face was defined as including the area on the forehead to the original hairline, on the cheek to the jawline vertically and laterally from the corner of the mouth to the tragus. The area Face did not include the surface area of the lips, scalp, ears, or neck, but included the nose and eyelids. Body surface area assessment was performed by the Palmar Method. Body surface area was estimated to the nearest 0.1%. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in F-BSA Repigmentation at Weeks 52, 104, and 156 | F-BSA involvement was the proportion of the facial body surface area with vitiligo. The area Face was defined as including the area on the forehead to the original hairline, on the cheek to the jawline vertically and laterally from the corner of the mouth to the tragus. The area Face did not include the surface area of the lips, scalp, ears, or neck, but included the nose and eyelids. Body surface area assessment was performed by the Palmar Method. Body surface area was estimated to the nearest 0.1%. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Weeks 52, 104, and 156 | 
| Percentage Change From Baseline in T-BSA Repigmentation at Week 24 | T-BSA involvement was the proportion of the body surface area with vitiligo. Body surface area assessment was performed by the Palmar Method. Body surface area was estimated to the nearest 0.1%. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in T-BSA Repigmentation at Weeks 52, 104, and 156 | T-BSA involvement was the proportion of the body surface area with vitiligo. Body surface area assessment was performed by the Palmar Method. Body surface area was estimated to the nearest 0.1%. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Percentage change = ([post-Baseline value minus Baseline value]/Baseline value) X 100. | Baseline; Weeks 52, 104, and 156 | 
| Mean Change From Baseline in T-VASI Score at Week 24 | T-VASI was calculated with contributions from 6 sites. The percentage of vitiligo involvement was estimated in hand units (percentage of BSA estimated to nearest 0.1%) by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate percent BSA vitiligo involvement. The degree of depigmentation for each site was estimated to the nearest percentage: 0% (no depigmentation present), 10% (only specks of depigmentation present), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site and summing the values (range: 0-100; lower scores indicate increased improvement). Change from Baseline (BL) was calculated as the post-BL value minus the BL value. | Baseline; Week 24 | 
| Mean Change From Baseline in T-VASI Score at Weeks 52, 104, and 156 | T-VASI was calculated with contributions from 6 sites. The percentage of vitiligo involvement was estimated in hand units (percentage of BSA estimated to nearest 0.1%) by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate percent BSA vitiligo involvement. The degree of depigmentation for each site was estimated to the nearest percentage: 0% (no depigmentation present), 10% (only specks of depigmentation present), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site and summing the values (range: 0-100; lower scores indicate increased improvement). Change from BL was calculated as the post-BL value minus the BL value. | Baseline; Weeks 52, 104, and 156 | 
| Percentage Change From Baseline in T-VASI Score at Week 24 | T-VASI was calculated with contributions from 6 sites. The percentage of vitiligo involvement was estimated in hand units (percentage of BSA estimated to nearest 0.1%) by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate percent BSA vitiligo involvement. The degree of depigmentation for each site was estimated to the nearest percentage: 0% (no depigmentation present), 10% (only specks of depigmentation present), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site and summing the values (range: 0-100; lower scores indicate increased improvement). | Baseline; Week 24 | 
| Percentage Change From Baseline in T-VASI Score at Weeks 52, 104, and 156 | T-VASI was calculated with contributions from 6 sites. The percentage of vitiligo involvement was estimated in hand units (percentage of BSA estimated to nearest 0.1%) by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate percent BSA vitiligo involvement. The degree of depigmentation for each site was estimated to the nearest percentage: 0% (no depigmentation present), 10% (only specks of depigmentation present), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site and summing the values (range: 0-100; lower scores indicate increased improvement). | Baseline; Weeks 52, 104, and 156 | 
| Mean Change From Baseline in Vitiligo European Task Force (VETF) Scale Scores at Week 24: Total Spreading | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Week 24 | 
| Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Spreading | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Weeks 52 and 104 | 
| Mean Change From Baseline in VETF Scale Scores at Week 24: Total Percentage Area | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Week 24 | 
| Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Percentage Area | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Weeks 52 and 104 | 
| Percentage Change From Baseline in VETF Scale Scores at Week 24: Total Percentage Area | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Week 24 | 
| Percentage Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Percentage Area | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Weeks 52 and 104 | 
| Mean Change From Baseline in VETF Scale Scores at Week 24: Total Staging | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Week 24 | 
| Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Staging | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Weeks 52 and 104 | 
| Percentage Change From Baseline in VETF Scale Scores at Week 24: Total Staging | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Week 24 | 
| Percentage Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Staging | The VETF-proposed system combines analysis of extent (0%-100% BSA), stage of disease (staging), and disease progression (spreading); each component is evaluated and reported independently. Staging is based on cutaneous and hair pigmentation in vitiligo patches. Disease is staged 0 to 4 on the largest macule in each of 5 body regions, except hands and feet, which are assessed separately and globally as 1 unique area. Stage 0=normal pigmentation, Stage 1=incomplete pigmentation, Stage 2=complete depigmentation (a few white hairs do not change stage), Stage 3=partial hair whitening (<30%), Stage 4=complete hair whitening; total score of 0 (less severe disease) to 20 (more severe disease). Disease progression is based on assessing the largest patch in each of 5 body areas: -1=regressive vitiligo (ongoing subclinical repigmentation), 0=similar limits, 1=progressive vitiligo (ongoing subclinical depigmentation); total score of -5 (improving disease) to +5 (more severe disease spread). | Baseline; Weeks 52 and 104 | 
| Percentage of Participants in Each Facial Assessment of the Physician's Global Vitiligo Assessment (F-PhGVA) Category at Week 24 | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. | Week 24 | 
| Percentage of Participants in Each Facial Assessment of the PhGVA (F-PhGVA) Category at Weeks 52, 104 and 156 | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. | Weeks 52, 104, and 156 | 
| Percentage of Participants in Each Total Body Assessment of the PhGVA (T-PhGVA) Category at Week 24 | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. | Week 24 | 
| Percentage of Participants in Each Total Body Assessment of the PhGVA (T-PhGVA) Category at Weeks 52, 104 and 156 | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. | Weeks 52, 104, and 156 | 
| Percentage of Participants in Each Facial Assessment of the Patient's Global Vitiligo Assessment (F-PaGVA) Category at Week 24 | The severity of vitiligo was assessed by the participant using the PaGVA, which has a 5-point scale. The participant was asked the following: How severe is your vitiligo on your face (or total body) with respect to the area covered by white skin? Responses: 0=no white patches (no vitiligo); 1=mild; 2=moderate; 3=severe; 4=very severe. | Week 24 | 
| Percentage of Participants in Each Facial Assessment of the PaGVA (F-PaGVA) Category at Weeks 52, 104, and 156 | The severity of vitiligo was assessed by the participant using the PaGVA, which has a 5-point scale. The participant was asked the following: How severe is your vitiligo on your face (or total body) with respect to the area covered by white skin? Responses: 0=no white patches (no vitiligo); 1=mild; 2=moderate; 3=severe; 4=very severe. | Weeks 52, 104, and 156 | 
| Percentage of Participants in Each Total Body Assessment of the PaGVA (T-PaGVA) Category at Week 24 | The severity of vitiligo was assessed by the participant using the PaGVA, which has a 5-point scale. The participant was asked the following: How severe is your vitiligo on your face (or total body) with respect to the area covered by white skin? Responses: 0=no white patches (no vitiligo); 1=mild; 2=moderate; 3=severe; 4=very severe. | Week 24 | 
| Percentage of Participants in Each Total Body Assessment of the PaGVA (T-PaGVA) Category at Weeks 52, 104, and 156 | The severity of vitiligo was assessed by the participant using the PaGVA, which has a 5-point scale. The participant was asked the following: How severe is your vitiligo on your face (or total body) with respect to the area covered by white skin? Responses: 0=no white patches (no vitiligo); 1=mild; 2=moderate; 3=severe; 4=very severe. | Weeks 52, 104, and 156 | 
| Percentage of Participants in Each Patient Global Impression of Change for Vitiligo (PaGIC-V) Category at Week 24 | The PaGIC-V is an assessment of improvement by the participant. It is a 7-point scale comparing the vitiligo areas at Baseline with the participant's treated areas of vitiligo at the study visit. The participant answered the following: Since the start of the treatment you've received in this study, your vitiligo in areas treated with the study drug is: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. | Baseline; Week 24 | 
| Percentage of Participants in Each PaGIC-V Category at Weeks 52, 104, and 156 | The PaGIC-V is an assessment of improvement by the participant. It is a 7-point scale comparing the vitiligo areas at Baseline with the participant's treated areas of vitiligo at the study visit. The participant answered the following: Since the start of the treatment you've received in this study, your vitiligo in areas treated with the study drug is: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. | Baseline; Weeks 52, 104, and 156 | 
| Percentage of Participants Who Report a PaGIC-V Score of Very Much Improved or Much Improved at Week 24 | The PaGIC-V is an assessment of improvement by the participant. It is a 7-point scale comparing the vitiligo areas at Baseline with the participant's treated areas of vitiligo at the study visit. The participant answered the following: Since the start of the treatment you've received in this study, your vitiligo in areas treated with the study drug is: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. | Baseline; Week 24 | 
| Percentage of Participants Who Report a PaGIC-V Score of Very Much Improved or Much Improved at Weeks 52, 104, and 156 | The PaGIC-V is an assessment of improvement by the participant. It is a 7-point scale comparing the vitiligo areas at Baseline with the participant's treated areas of vitiligo at the study visit. The participant answered the following: Since the start of the treatment you've received in this study, your vitiligo in areas treated with the study drug is: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. | Baseline; Weeks 52, 104, and 156 | 
| Time to Achieve an F-VASI50: Number of Days From the Date of the First Application in the Double-Blind Period to the Date of the First Evaluation at Which the Participant Met the F-VASI50 Score | An F-VASI50 responder achieved at least 50% improvement from Baseline in F-VASI, measured by the percentage of vitiligo involvement (percentage of BSA) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment), or 100% (no pigment). The percentage of BSA (hand unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator using the Palmar Method. The Investigator used his/her hand to mimic the participant's hand size to evaluate the percentage of BSA vitiligo involvement. F-VASI was then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each site on the face and summing the values of all sites (possible range: 0-3; lower scores indicate increased improvement). | up to 52 weeks | 
| Time to Achieve a T-VASI50: Number of Days From the Date of the First Application in the Double-Blind Period to the Date of the First Evaluation at Which the Participant Met the T-VASI50 Score | A T-VASI50 responder achieved at least 50% improvement from Baseline in T-VASI. T-VASI was measured by the percentage of vitiligo involvement from all body regions (percentage of BSA; assessed by the Investigator) and the degree of depigmentation: 0% (no depigmentation), 10% (only specks of depigmentation), 25% (pigmented area exceeded depigmented area), 50% (depigmented and pigmented area was equal), 75% (depigmented area exceeded pigmented area), 90% (specks of pigment present), 100% (no pigment present). T-VASI was derived by multiplying the vitiligo involvement values by the percentage of affected skin for each body site and summing all values (possible range: 0-100; lower scores indicate increased improvement). | up to 52 weeks | 
| Time to Achieve an F-PhGVA of Clear or Almost Clear | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. Time to achieve an F-PhGVA response was defined as the number of days from the date of the first application in the Double-Blind Period to the date of the first evaluation at which the participant met the F-PhGVA score. | up to 52 weeks | 
| Time to Achieve an T-PhGVA of Clear or Almost Clear | The severity of vitiligo was assessed by the physician using the PhGVA, which has a 5-point scale. 0=clear, no signs of vitiligo; 1=almost clear, only specks of depigmentation present; 2=mild disease, pigmented and depigmented areas are equal; 3=moderate disease, more or complete depigmentation (may include < 30% hair whitening); 4=severe disease, complete depigmentation plus > 30% hair whitening. Time to achieve a T-PhGVA response was defined as the number of days from the date of the first application in the Double-Blind Period to the date of the first evaluation at which the participant met the T-PhGVA score. | up to 52 weeks | 
| Time to Achieve a PaGIC-V of Very Much Improved or Much Improved | The PaGIC-V is an assessment of improvement by the participant. It is a 7-point scale comparing the vitiligo areas at Baseline with the participant's treated areas of vitiligo at the study visit. The participant answered the following: Since the start of the treatment you've received in this study, your vitiligo in areas treated with the study drug is: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. Time to achieve a PaGIC-V response was defined as the number of days from the date of the first application in the Double-Blind Period to the date of the first evaluation at which the participant met the PaGIC-V score. | up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitiligo, depigmenting disorder, topical JAK inhibitor