Topical Ruxolitinib Evaluation in Vitiligo Study 1 (TRuE-V1)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib cream in adolescent and adult participants with non-segmental vitiligo for whom total body involved vitiligo area (facial and nonfacial) does not exceed 10% body surface area (BSA).

Official Title
-----------------
Topical Ruxolitinib Evaluation in Vitiligo Study 1 (TRuE-V1): A Phase 3, Double-Blind, Randomized, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream Followed by an Extension Period in Participants With Vitiligo

Conditions
-----------------
Non-segmental Vitiligo

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Clinical diagnosis of non-segmental vitiligo with depigmented area including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, ≥ 3 T-VASI, and total body vitiligo area (facial and nonfacial) not exceeding 10% BSA. Agree to discontinue all agents used to treat vitiligo from screening through the final safety follow-up visit. Over-the-counter preparations deemed acceptable by the investigator and camouflage makeups are permitted. Must be willing to take appropriate contraceptive measures to avoid pregnancy or fathering a child for the duration of study participation. Key Exclusion Criteria: No pigmented hair within any of the vitiligo areas on the face. Other forms of vitiligo (eg, segmental) or other differential diagnosis of vitiligo or other skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor). Have used depigmentation treatments (eg, monobenzone) for past treatment of vitiligo or other pigmented areas. Use of protocol-defined treatments within the indicated washout period before baseline.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will receive ruxolitinib cream or vehicle for 24 weeks, after which they will be offered the opportunity to continue in the treatment extension period. Participants initially randomized to vehicle will be crossed over to active drug, and participants treated with ruxolitinib cream will receive an additional 28 weeks of treatment with ruxolitinib cream.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-Blind Period: Ruxolitinib cream 1.5% BID<br>Participants applied ruxolitinib 1.5% cream twice daily (BID) for 24 weeks. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;|
| Placebo Comparator: Double-Blind Period: Vehicle cream BID<br>Participants applied matching vehicle cream BID for 24 weeks. | Drug: Vehicle<br>* Vehicle cream is a topical formulation applied as a thin film to affected areas.<br>|
| Experimental: Treatment-Extension Period: Ruxolitinib cream 1.5% BID<br>Participants who completed the Week 24 assessments with no safety concerns could continue into the 28-week Treatment-Extension Period. Participants who applied ruxolitinib cream 1.5% BID during the Double-Blind Period continued to apply ruxolitinib cream 1.5% BID for an additional 28 weeks in the Treatment-Extension Period. | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;|
| Experimental: Treatment-Extension Period: Vehicle cream to Ruxolitinib cream 1.5% BID<br>Participants who completed the Week 24 assessments with no safety concerns could continue into the 28-week Treatment-Extension Period. Participants who applied vehicle cream BID during the Double-Blind Period applied ruxolitinib cream 1.5%m BID for 28 weeks in the Treatment-Extension Period. | 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<br>* Vehicle cream is a topical formulation applied as a thin film to affected areas.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a ≥ 75% Improvement From Baseline in the Face Vitiligo Area Scoring Index (F-VASI75) Score at Week 24 | An F-VASI75 responder achieved at least 75% 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 Achieving a ≥ 50% Improvement From Baseline in the Face Vitiligo Area Scoring Index (F-VASI50) Score 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 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 | 
| Percentage of Participants Achieving a ≥ 90% Improvement From Baseline in the Face Vitiligo Area Scoring Index (F-VASI90) Score at Week 24 | An F-VASI90 responder achieved at least 90% 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; Week 24 | 
| Percentage of Participants Achieving a ≥ 50% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI50) Score at Week 24 | A T-VASI50 responder achieved at least 50% improvement from Baseline in T-VASI, calculated with contributions from 6 sites. The percentage of vitiligo involvement was estimated in hand units (percentage of BSA 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 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 of Participants Achieving a Vitiligo Noticeability Scale (VNS) of 4 or 5 at Week 24 | The VNS is a patient-reported measure of vitiligo treatment success that is rated on a 5-point scale. The Baseline facial photograph was shown to the participants for reference, and a mirror was provided for the participants to assess the vitiligo on their face. The participant was asked to respond to the following query: Compared with before treatment, how noticeable is the vitiligo now? Responses: (1) more noticeable, (2) as noticeable, (3) slightly less noticeable, (4) a lot less noticeable, and (5) no longer noticeable. | Baseline; Week 24 | 
| Percentage Change From Baseline in Facial Body Surface Area (F-BSA) 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 to the jawline and laterally from the corner of the mouth to the tragus. The area Face did not include 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 (BL) value minus BL value]/BL value) X 100. | Baseline; Week 24 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period | 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. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. | from the time of Informed Consent Form signing until at least 30 days after the last application of study drug (up to Week 24) | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Treatment-Extension Period | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. | from the completion of the Week 24 assessments until at least 30 days after the last application of study drug (up to Week 52 + 30 days) | 
| Percentage of Participants Achieving a ≥ 25% Improvement in the Face Vitiligo Area Scoring Index (F-VASI25) Score at Week 24 | An F-VASI25 responder achieved at least 25% 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; Week 24 | 
| Percentage of Participants Achieving a ≥ %25, ≥ %50, ≥ 75%, and ≥ 90% Improvement in the Face Vitiligo Area Scoring Index (F-VASI25/50/75/90) Score at Week 52 | An F-VASI25/50/75/90 responder achieved at least 25/50/75/90% 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; Week 52 | 
| Percentage Change From Baseline in F-VASI 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-BL value minus BL value]/BL value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in F-VASI at Week 52 | 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-BL value minus BL value]/BL value) X 100. | Baseline; Week 52 | 
| Percentage Change From Baseline in F-BSA at Week 52 | 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 to the jawline and laterally from the corner of the mouth to the tragus. The area Face did not include 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-BL value minus BL value]/BL value) X 100. | Baseline; Week 52 | 
| Percentage Change From Baseline in T-VASI 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). Percentage change = ([post-BL value minus BL value]/BL value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in T-VASI at Week 52 | 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 = ([post-BL value minus BL value]/BL value) X 100. | Baseline; Week 52 | 
| Percentage Change From Baseline in T-BSA 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-BL value minus BL value]/BL value) X 100. | Baseline; Week 24 | 
| Percentage Change From Baseline in T-BSA at Week 52 | 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-BL value minus BL value]/BL value) X 100. | Baseline; Week 52 | 
| Percentage of Participants Achieving a ≥ 25%, ≥ 75%, and ≥ 90% Improvement in the Total Body Vitiligo Area Scoring Index (T-VASI25/75/90) Score at Week 24 | A T-VASI25/75/90 responder achieved at least 25/75/90% improvement from Baseline in T-VASI, 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 of Participants Achieving a ≥ 25%, ≥ 50%, ≥ 75%, and ≥ 90% Improvement in the Total Body Vitiligo Area Scoring Index (T-VASI25/50/75/90) Score at Week 52 | A T-VASI25/50/75/90 responder achieved ≥25/50/75/90% improvement from Baseline in T-VASI, 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 52 | 
| Percentage of Participants in Each Category of VNS During the Treatment Period (Double-Blind and Treatment-Extension Periods) | The VNS is a patient-reported measure of vitiligo treatment success that is rated on a 5-point scale. The Baseline facial photograph was shown to the participants for reference, and a mirror was provided for the participants to assess the vitiligo on their face. The participant was asked to respond to the following query: Compared with before treatment, how noticeable is the vitiligo now? Responses: (1) more noticeable, (2) as noticeable, (3) slightly less noticeable, (4) a lot less noticeable, and (5) no longer noticeable. | Baseline; Week 24 and Week 52 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 24 | The DLQI is a 10-question validated questionnaire for use in participants aged 16 years and over to measure how much the skin problem has affected the participant over the previous 7 days. Each question is scored as: very much = 3; a lot = 2; a little = 1; not at all = 0; not relevant = 0. For Question 7, Prevented work or studying = 3. The DLQI was calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Baseline; Week 24 | 
| Change From Baseline in DLQI at Week 52 | The DLQI is a 10-question validated questionnaire for use in participants aged 16 years and over to measure how much the skin problem has affected the participant over the previous 7 days. Each question is scored as: very much = 3; a lot = 2; a little = 1; not at all = 0; not relevant = 0. For Question 7, Prevented work or studying = 3. The DLQI was calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Baseline; Week 52 | 
| Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) During the Treatment Period (Double-Blind and Treatment-Extension Periods) | The DLQI is a 10-question validated questionnaire for use in participants aged 16 years and over to measure how much the skin problem has affected the participant over the previous 7 days. The CDLQI is the youth/children's version of the DLQI and was completed by adolescents aged ≥ 12 years to < 16 years. Each question is scored as: very much = 3; quite a lot = 2; only a little = 1; not at all = 0; question unanswered = 0. For Question 7: Prevented school = 3. The CDLQI was calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Baseline; Week 24 and Week 52 | 
| Trough Plasma Concentrations of Ruxolitinib at Weeks 4, 24, and 40 | Trough plasma concentration was defined as the measurement of the plasma concentration of ruxolitinib before drug application. | pre-dose at Weeks 4, 24, and 40 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitiligo, non-segmental, JAK inhibitor