A Study of INCB018424 Phosphate Cream in Subjects With Vitiligo

Phase 2

Completed

Conditions: Vitiligo

Interventions: Drug: Ruxolitinib cream
Drug: Vehicle cream

Registration Number: NCT03099304

Lead Sponsor: Incyte Corporation

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 157

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Ruxolitinib cream 0.5% QD	Ruxolitinib cream	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.
Ruxolitinib cream 0.15% QD	Ruxolitinib cream	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.
Ruxolitinib cream 1.5% twice daily (BID)	Ruxolitinib cream	Ruxolitinib cream 1.5% BID for 52 weeks, followed by ruxolitinib cream 1.5% BID in a 104-week open-label extension.
Ruxolitinib cream 0.15% QD	Vehicle cream	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.
Vehicle BID	Ruxolitinib cream	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.
Ruxolitinib cream 1.5% once daily (QD)	Ruxolitinib cream	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.
Vehicle BID	Vehicle cream	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.
Ruxolitinib cream 1.5% once daily (QD)	Vehicle cream	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.
Ruxolitinib cream 0.5% QD	Vehicle cream	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline; 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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE up to Week 52	up to 52 weeks	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.
Percentage of Participants Who Achieved a Facial Assessment of the Physician's Global Vitiligo Assessment (F-PhGVA) of Clear or Almost Clear	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.
Dose Response on Percentage Change From Baseline in F-VASI	up to 156 weeks
Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE From Week 24 to Week 52	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.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Grade 3 or Higher TEAE up to Week 24	up to 24 weeks	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.
Percentage of Participants Who Achieved an F-VASI50 at Weeks 52, 104, and 156	Baseline; 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).
Mean Change From Baseline in T-VASI Score at Week 24	Baseline; 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.
Number of Participants Who Applied Ruxolitinib 1.5% Cream BID Throughout Study Participation With Any TEAE and Any Grade 3 or Higher TEAE	up 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.
Percentage Change From Baseline in T-BSA Repigmentation at Weeks 52, 104, and 156	Baseline; 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.
Percentage Change From Baseline in T-VASI Score at Week 24	Baseline; 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).
Percentage Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Percentage Area	Baseline; Weeks 52 and 104	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).
Mean Change From Baseline in VETF Scale Scores at Week 24: Total Staging	Baseline; Week 24	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).
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	Baseline; 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).
Mean Change From Baseline in F-VASI Score at Weeks 52, 104, and 156	Baseline; 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.
Percentage Change From Baseline in F-VASI Score at Week 24	Baseline; 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.
Percentage Change From Baseline in F-BSA Repigmentation at Week 24	Baseline; 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.
Mean Change From Baseline in Vitiligo European Task Force (VETF) Scale Scores at Week 24: Total Spreading	Baseline; Week 24	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).
Number of Participants With Any TEAE and Any Grade 3 or Higher TEAE From Week 52 to Week 156	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.
Percentage Change From Baseline in T-BSA Repigmentation at Week 24	Baseline; 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.
Mean Change From Baseline in T-VASI Score at Weeks 52, 104, and 156	Baseline; 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.
Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Staging	Baseline; Weeks 52 and 104	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).
Percentage of Participants in Each Facial Assessment of the Physician's Global Vitiligo Assessment (F-PhGVA) Category at Week 24	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.
Mean Change From Baseline in F-VASI Score at Week 24	Baseline; 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.
Percentage Change From Baseline in F-VASI Score at Weeks 52, 104, and 156	Baseline; 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.
Percentage Change From Baseline in F-BSA Repigmentation at Weeks 52, 104, and 156	Baseline; 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.
Percentage Change From Baseline in T-VASI Score at Weeks 52, 104, and 156	Baseline; 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).
Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Spreading	Baseline; Weeks 52 and 104	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).
Mean Change From Baseline in VETF Scale Scores at Week 24: Total Percentage Area	Baseline; Week 24	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).
Percentage Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Staging	Baseline; Weeks 52 and 104	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).
Percentage of Participants in Each Patient Global Impression of Change for Vitiligo (PaGIC-V) Category at Week 24	Baseline; 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.
Percentage of Participants in Each PaGIC-V Category at Weeks 52, 104, and 156	Baseline; 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.
Time to Achieve an T-PhGVA of Clear or Almost Clear	up to 52 weeks	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.
Mean Change From Baseline in VETF Scale Scores at Weeks 52 and 104: Total Percentage Area	Baseline; Weeks 52 and 104	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).
Percentage Change From Baseline in VETF Scale Scores at Week 24: Total Percentage Area	Baseline; Week 24	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).
Percentage of Participants in Each Total Body Assessment of the PhGVA (T-PhGVA) Category at Week 24	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.
Percentage of Participants in Each Facial Assessment of the PaGVA (F-PaGVA) Category at Weeks 52, 104, and 156	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.
Percentage of Participants Who Report a PaGIC-V Score of Very Much Improved or Much Improved at Weeks 52, 104, and 156	Baseline; 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.
Time to Achieve an F-PhGVA of Clear or Almost Clear	up to 52 weeks	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.
Percentage Change From Baseline in VETF Scale Scores at Week 24: Total Staging	Baseline; Week 24	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).
Percentage of Participants in Each Total Body Assessment of the PaGVA (T-PaGVA) Category at Week 24	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.
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	up to 52 weeks	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).
Percentage of Participants in Each Facial Assessment of the PhGVA (F-PhGVA) Category at Weeks 52, 104 and 156	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.
Percentage of Participants in Each Total Body Assessment of the PhGVA (T-PhGVA) Category at Weeks 52, 104 and 156	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.
Percentage of Participants in Each Total Body Assessment of the PaGVA (T-PaGVA) Category at Weeks 52, 104, and 156	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.
Percentage of Participants Who Report a PaGIC-V Score of Very Much Improved or Much Improved at Week 24	Baseline; 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.
Percentage of Participants in Each Facial Assessment of the Patient's Global Vitiligo Assessment (F-PaGVA) Category at Week 24	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.
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	up to 52 weeks	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).
Time to Achieve a PaGIC-V of Very Much Improved or Much Improved	up to 52 weeks	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.

Trial Locations

Locations (26): NORTHWESTERN UNIVERSITY, 676 N Saint Clair
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Chicago, Illinois, United States
WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DERMATOLOGY, 969 N. Mason Road
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Saint Louis, Missouri, United States
CENTRAL SOONER RESEARCH, 900 N Porter Ave
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Norman, Oklahoma, United States
DAWES FRETZIN CLINICAL RESEARCH GROUP, 8103 Clearvista Parkway
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Indianapolis, Indiana, United States
HAMZAVI DERMATOLOGY, 3031 W Grand Blvd
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Detroit, Michigan, United States
UNIVERSITY OF ALABAMA AT BIRMINGHAM (UAB), 1802 6th Ave S
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Birmingham, Alabama, United States
NORTHWEST AR CLINICAL TRIALS CENTER, PLLC/HULL DERMATOLOGY, PA, 500 S 52nd Street
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Rogers, Arkansas, United States
THE VITILIGO & PIGMENTATION INSTITUE OF SOUTHERN CALIFORNIA, 5670 Wilshire Boulevard
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Los Angeles, California, United States
DERMATOLOGY RESEARCH ASSOCIATES- LOS ANGELES, 8930 S Sepulveda Blvd
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Los Angeles, California, United States
DERMATOLOGY SPECIALISTS, 3629 Vista Way
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Oceanside, California, United States
LEAVITT MEDICAL ASSOCIATES OF FLORIDA INC/ AMERIDERM RESEARCH, 725 W Granada Blvd
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Ormond Beach, Florida, United States
EMORY UNIVERSITY, 1525 Clifton Road
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Atlanta, Georgia, United States
DS RESEARCH, 2241 Green Valley Road
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New Albany, Indiana, United States
TULANE UNIVERSITY, 1415 Tulane Avenue
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New Orleans, Louisiana, United States
Tufts Medical Center, 260 Tremont Street
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Boston, Massachusetts, United States
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI MEDICAL CENTER- DERMATOLOGY ASSOCIATES, 5 E 98th Street
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New York, New York, United States
ACTIVMED PRACTICES & RESEARCH, INC, 110 Corporate Drive
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Portsmouth, New Hampshire, United States
WAKE FOREST UNIVERSITY HEALTH SCIENCES, Medical Center Boulevard
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Winston-Salem, North Carolina, United States
RHODE ISLAND HOSPITAL, 593 Eddy Street
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Providence, Rhode Island, United States
ARLINGTON RESEARCH CENTER, INC., 711 East Lamar Boulevard
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Arlington, Texas, United States
MENTER DERMATOLOGY RESEARCH INSTITUTE, 3900 Junius Street
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Dallas, Texas, United States
UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, DEPARTMENT OF DERMATOLOGY, 5323 Harry Hines Blvd
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Dallas, Texas, United States
THE DERMATOLOGY AND LASER CENTER OF SAN ANTONIO, 7810 Louis Pasteur
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San Antonio, Texas, United States
CLINICAL RESEARCH CENTER OF CT, 27 Hospital Avenue
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Danbury, Connecticut, United States
BURKE PHARMACEUTICAL RESEARCH LLC, 3633 Central Ave
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Hot Springs, Arkansas, United States
UNIVERSITY OF MASSACHUESETTS, 364 Plantation Street
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Worcester, Massachusetts, United States