A Phase 2b Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Active Non-segmental Vitiligo Subjects

• ClinicalTrials.gov Identifier: NCT03715829
• Recruitment Status: Completed
• First Posted: October 23, 2018
• Results First Posted: March 25, 2022
• Last Update Posted: March 25, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This is a Phase 2b, randomized, double blind, parallel group, multicenter study with an extension period. The study will have a maximum duration of approximately 60 weeks. This includes an up to 4 weeks Screening Period, a 24 week dose ranging period, an up to 24 week extension period and a 8 week Follow up Period.

Condition or disease	Intervention/treatment	Phase
Active Non-segmental Vitiligo	Drug: PF-06651600; Drug: placebo; Drug: PF06700841; Device: narrow-band UVB phototherapy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 366 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Dose ranging period is a parallel design. Extension period is a sequential design.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Dose ranging period is blinded. The partially blinded extension period includes open arms and blinded arms.
• Primary Purpose: Treatment
• Official Title: A PHASE 2B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-06651600 WITH A PARTIALLY BLINDED EXTENSION PERIOD TO EVALUATE THE EFFICACY AND SAFETY OF PF-06651600 AND PF-06700841 IN SUBJECTS WITH ACTIVE NON-SEGMENTAL VITILIGO
• Actual Study Start Date: November 26, 2018
• Actual Primary Completion Date: February 5, 2021
• Actual Study Completion Date: February 5, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Induction dose 1 given once a day(QD) for 4 weeks followed by maintenance dose A given QD for 20 weeks	Drug: PF-06651600; Induction dose 1. Oral tablet taken QD; Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD
Experimental: Cohort 2; Induction dose 2 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks	Drug: PF-06651600; Induction dose 2. Oral tablet taken QD; Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD
Experimental: Cohort 3; Maintenance dose A given QD for 24 weeks	Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD
Experimental: Cohort 4; Maintenance dose B given QD for 24 weeks	Drug: PF-06651600; Maintenance Dose B. Oral tablet taken QD
Experimental: Cohort 5; Maintenance dose C given QD for 24 weeks	Drug: PF-06651600; Maintenance Dose C. Oral tablet taken QD
Placebo Comparator: Cohort 6; Placebo given QD for 24 weeks	Drug: placebo; placebo
Experimental: Extension Cohort 1; 4 week drug holiday (no drug given) followed by PF-06700841 oral tablet QD for 20 weeks	Drug: PF06700841; Oral tablet taken QD
Experimental: Extension Cohort 2; Induction dose 1 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks in conjunction with narrow band UVB phototherapy	Drug: PF-06651600; Induction dose 1. Oral tablet taken QD; Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD; Device: narrow-band UVB phototherapy; Phototherapy will be combined with PF-06651600
Experimental: Extension Cohort 3; Induction dose 1 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks	Drug: PF-06651600; Induction dose 1. Oral tablet taken QD; Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD
Experimental: Extension Cohort 4; Maintenance dose A given QD for 24 weeks	Drug: PF-06651600; Maintenance dose A. Oral tablet taken QD
Experimental: Extension Cohort 5; Maintenance dose B given QD for 24 weeks	Drug: PF-06651600; Maintenance Dose B. Oral tablet taken QD
No Intervention: Extension Cohort 6; Observation period for 24 weeks

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Central Read Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 - Dose Ranging (DR) Period [ Time Frame: Baseline, Week 24 (Baseline was defined as the last measurement prior to Study Day 18) ]
   Central read F-VASI was assessed based on the facial photographs taken at the site. Central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area. The higher score of F-VASI signified severer symptoms of non-segmental vitiligo. Percent change from baseline in central read F-VASI = ((post-baseline central read F-VASI - baseline central read F-VASI)/baseline central read F-VASI)×100. A negative percent change from baseline in central read F-VASI signified an improvement.
2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) up to Week 24 - DR Period [ Time Frame: 24 weeks ]
   Adverse Event (AE) was defined as any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. SAE was defined as any untoward medical occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; or that was considered to be an important medical event. Causality to study treatment was determined by the investigator.
3. Number of Participants With the TEAEs of Anaemia, Neutropenia, Thrombocytopenia and Lymphopenia - DR Period [ Time Frame: Baseline up to Week 24 ]

   An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. The abnormal test findings, clinically significant signs and symptoms of anaemia, neutropenia, thrombocytopenia and lymphopenia were reported as AEs. The clinical significance was determined by the investigator.

   An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs.

   Baseline was defined as the last measurement prior to first dosing (Day 1).

4. Number of Participants With Clinically Meaningful Changes From Baseline in Lipid Profile up to Week 24 - DR Period [ Time Frame: Baseline up to Week 24 ]

   Participants had to abstain from all food and drink (except water and non-investigational products) for an 8-hour overnight fast prior to fasting lipid profile panel collection. Fasting lipid assessment included total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. The clinical meaningfulness was determined by the investigator.

   Baseline was defined as the last measurement prior to first dosing (Day 1).

5. Number of Participants With Liver Function Test Values Meeting the Protocol-Specified Discontinuation Criteria - DR Period [ Time Frame: 24 weeks ]
   Liver function tests included tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin.
6. Number of Participants With TEAEs and SAEs - Extension (Ext) Period [ Time Frame: 24 weeks ]
   AE was defined as any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. SAE was defined as any untoward medical occurrence at any dose that resulted in death; was life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; or that was considered to be an important medical event. Causality to study treatment was determined by the investigator.
7. Number of Participants With the TEAEs of Anaemia, Neutropenia, Thrombocytopenia and Lymphopenia - Ext Period [ Time Frame: 24 weeks ]

   An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. The abnormal test findings, clinically significant signs and symptoms of anaemia, neutropenia, thrombocytopenia and lymphopenia were reported as AEs. The clinical significance was determined by the investigator.

   An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs.

8. Number of Participants With Clinically Meaningful Changes From Baseline in Lipid Profile - Ext Period [ Time Frame: 24 Weeks ]
   Participants had to abstain from all food and drink (except water and non-investigational products) for an 8-hour overnight fast prior to fasting lipid profile panel collection. Fasting lipid assessment included total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. The clinical meaningfulness was determined by the investigator.
9. Number of Participants With Liver Function Test Values Meeting the Protocol-Specified Discontinuation Criteria - Ext Period [ Time Frame: 24 weeks ]
   Liver function tests included tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin.

Secondary Outcome Measures :

1. Percentage of Participants Achieving Central F-VASI75 at Week 24 - DR Period [ Time Frame: Week 24 ]

   This outcome measure was the percentage of participants achieving at least 75% improvement from baseline in central read F-VASI (F-VASI75) at Week 24. A negative percent change from baseline in central read F-VASI signified an improvement. The central read F-VASI75 response rate was analyzed by first treating the missing data (non-COVID-19 related) as non responders and then applying Chan and Zhang exact confidence interval (CI) method at Week 24.

   Central read F-VASI75=1 if percent change from baseline ≥75; central read F-VASI75=0 if percent change from baseline <75. Percent change from baseline in F-VASI=((post-baseline F-VASI - baseline F-VASI)/baseline F-VASI)×100. Baseline was defined as the last measurement prior to study Day 18.

2. Percentage of Participants Achieving T-VASI50 at Week 24 - DR Period [ Time Frame: Week 24 ]
   Total body VASI (T-VASI) was calculated using a formula that included contribution from 6 different body regions (possible range, 0-100) with a modified method: T-VASI= Ʃ[Hand Units]×[Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 separate and mutually exclusive regions: face/neck, hands, upper extremities (excluding hands), trunk, lower extremities (excluding feet), and feet. The extent of depigmentation was expressed by percentages: 0, 10%, 25%, 50%, 75%, 90% or 100%. The data below was the percentage of participants achieving at least 50% improvement from baseline in T-VASI (T-VASI50) at Week 24. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
3. Percent Change From Baseline in T-VASI at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
   The T-VASI was calculated using a formula that included contribution from 6 different body regions (possible range, 0-100) with a modified method: VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 separate and mutually exclusive regions: face/neck, hands, upper extremities (excluding hands), trunk, lower extremities (excluding the feet), and feet. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. Percent change from baseline in T-VASI=((post-baseline T-VASI - baseline T-VASI)/baseline T-VASI)×100. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
4. Percent Change From Baseline in Central Read F-VASI at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ]

   The central read F-VASI was assessed based on the facial photographs taken at the site. The central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area.

   Percent change from baseline in central read F-VASI = ((post-baseline central read F-VASI - baseline central read F-VASI)/baseline central read F-VASI)×100. Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to Study Day 18.

5. Percent Change From Baseline in Local F-VASI at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]

   The site assessment of the F-VASI was calculated using a formula that included contribution from face (possible range, 0.00 4.00): Local F-VASI = [Digit Units] × [Depigmentation] × 0.1. Scalp, neck, eyebrows, eyelashes, and vermilion were excluded from this calculation. The volar surface of 1 digit (the participant's thumb) was approximately 0.1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of face. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%.

   Percent change from baseline in Local F-VASI = ((post baseline Local F-VASI - baseline Local F-VASI)/baseline Local F-VASI)×100. Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).

6. Percent Change From Baseline in SA-VES at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 16 and 24 ]
   The Self-Assessment Vitiligo Extent Score (SA-VES) was a validated patient report outcome measurement instrument to provide information about disease extent. Vitiligo Extent Score (VES) was a measure to express the overall vitiligo involvement of the body (extent). Clinical illustrations for 19 separate body areas that reflected different degrees of involvement (1%, 5%, 10%, 25%, 50% and 75% depigmentation) were chosen to represent the participant's skin lesions to get the total extent of the disease. VES was a sum of all surface measurement that was similar to VASI. Baseline was defined as the last measurement prior to first dosing (Day 1).
7. Absolute Change From Baseline in T-VASI at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]

   The T-VASI was calculated using a formula that included contribution from 6 different body regions (possible range, 0-100) with a modified method: VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 separate and mutually exclusive regions: face/neck, hands, upper extremities (excluding hands), trunk, lower extremities (excluding the feet), and feet. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%.

   The absolute change from baseline in T-VASI was analyzed using the ANCOVA analysis. Negative change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).

8. Percentage of Participants Achieving T-VASI50 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
   T-VASI was calculated by a formula that included contribution from 6 body regions (possible range, 0-100): T-VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 mutually exclusive regions: face/neck, hands, upper extremities, trunk, lower extremities, and feet. The extent of depigmentation was expressed by the percentages: 0, 10%, 25%, 50%, 75%, 90% or 100%. The outcome measure was the percentage of participants achieving at least 50% improvement from baseline in T-VASI (T-VASI50). Percent change from baseline in T-VASI=((post-baseline T-VASI - baseline T-VASI)/baseline T-VASI)×100. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
9. Percentage of Participants Achieving T-VASI75 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
   T-VASI was calculated by a formula that included contribution from 6 body regions (possible range, 0-100): T-VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 mutually exclusive regions: face/neck, hands, upper extremities, trunk, lower extremities, and feet. The extent of depigmentation was expressed by the percentages: 0, 10%, 25%, 50%, 75%, 90% or 100%. The outcome measure was the percentage of participants achieving at least 75% improvement from baseline in T-VASI (T-VASI75). Percent change from baseline in T-VASI=((post-baseline T-VASI - baseline T-VASI)/baseline T-VASI)×100. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
10. Percentage of Participants Achieving T-VASI90 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    T-VASI was calculated by a formula that included contribution from 6 body regions (possible range, 0-100): T-VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 mutually exclusive regions: face/neck, hands, upper extremities, trunk, lower extremities, and feet. The extent of depigmentation was expressed by the percentages: 0, 10%, 25%, 50%, 75%, 90% or 100%. The outcome measure was the percentage of participants achieving at least 90% improvement from baseline in T-VASI (T-VASI90). Percent change from baseline in T-VASI=((post-baseline T-VASI - baseline T-VASI)/baseline T-VASI)×100. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
11. Percentage of Participants Achieving T-VASI100 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    T-VASI was calculated using a formula that included contribution from 6 body regions (possible range, 0-100): T-VASI = Ʃ [Hand Units] × [Depigmentation]. One hand unit, which encompassed the palm plus the volar surface of all the digits, was approximately 1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of each body region. The body was divided into 6 mutually exclusive regions: face/neck, hands, upper extremities, trunk, lower extremities, and feet. The extent of depigmentation was expressed by the percentages: 0, 10%, 25%, 50%, 75%, 90% or 100%. This outcome measure was the percentage of participants achieving 100% improvement from baseline in T-VASI (T-VASI100). Percent change from baseline in T-VASI = ((post-baseline T-VASI - baseline T-VASI)/baseline T-VASI)×100. Negative percent change from baseline in T-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
12. Percentage of Participants Achieving Central Read F-VASI50 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ]
    The central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area. Percent change from baseline in F-VASI = ((post-baseline F-VASI - baseline F-VASI)/baseline F-VASI)×100. This outcome measure was the percentage of participants achieving at least 50% improvement in central read F-VASI from baseline (F-VASI50). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to Study Day 18.
13. Percentage of Participants Achieving Central Read F-VASI75 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ]
    The central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area. Percent change from baseline in F-VASI = ((post-baseline F-VASI - baseline F-VASI)/baseline F-VASI)×100. This outcome measure was the percentage of participants achieving at least 75% improvement in central read F-VASI from baseline (F-VASI75). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to Study Day 18.
14. Percentage of Participants Achieving Central Read F-VASI90 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ]
    The central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area. Percent change from baseline in F-VASI = ((post-baseline F-VASI - baseline F-VASI)/baseline F-VASI)×100. This outcome measure was the percentage of participants achieving at least 90% improvement in central read F-VASI from baseline (F-VASI90). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to Study Day 18.
15. Percentage of Participants Achieving Central Read F-VASI100 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ]
    The central read F-VASI was calculated using a formula that included contribution of affected facial surface areas showing all 6 different depigmentation rates (0.1, 0.25, 0.5, 0.75, 0.9 and 1) with a modified method: F-VASI (central read)=Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]. Face was defined as the area from the hairline on top of the forehead to the jawline at the bottom of the cheeks. F-VASI (central read) ranged from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as the value between 0.0 to 1.0) being 4% of total Body Surface Area. Percent change from baseline in F-VASI = ((post-baseline F-VASI - baseline F-VASI)/baseline F-VASI)×100. This outcome measure was the percentage of participants achieving at least 100% improvement in central read F-VASI from baseline (F-VASI100). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to Study Day 18.
16. Percentage of Participants Achieving Local F-VASI50 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    The site assessment of the F-VASI was calculated using a formula that included contribution from face (possible range, 0-4): Local F-VASI = [Digit Units] × [Depigmentation] × 0.1. Scalp, neck, eyebrows, eyelashes, and vermilion were excluded from this calculation. The volar surface of 1 digit (the participant's thumb) was approximately 0.1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of face. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. Percent change from baseline in Local F-VASI = ((post baseline Local F-VASI - baseline Local F-VASI)/baseline Local F-VASI)×100. This outcome measure was the percentage of participants achieving at least 50% improvement in site assessment F-VASI from baseline (F-VASI50). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
17. Percentage of Participants Achieving Local F-VASI75 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    The site assessment of the F-VASI was calculated using a formula that included contribution from face (possible range, 0-4): Local F-VASI = [Digit Units] × [Depigmentation] × 0.1. Scalp, neck, eyebrows, eyelashes, and vermilion were excluded from this calculation. The volar surface of 1 digit (the participant's thumb) was approximately 0.1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of face. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. Percent change from baseline in Local F-VASI = ((post baseline Local F-VASI - baseline Local F-VASI)/baseline Local F-VASI)×100. This outcome measure was the percentage of participants achieving at least 75% improvement in site assessment F-VASI from baseline (F-VASI75). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
18. Percentage of Participants Achieving Local F-VASI90 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    The site assessment of the F-VASI was calculated using a formula that included contribution from face (possible range, 0-4): Local F-VASI = [Digit Units] × [Depigmentation] × 0.1. Scalp, neck, eyebrows, eyelashes, and vermilion were excluded from this calculation. The volar surface of 1 digit (the participant's thumb) was approximately 0.1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of face. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. Percent change from baseline in Local F-VASI = ((post baseline Local F-VASI - baseline Local F-VASI)/baseline Local F-VASI)×100. This outcome measure was the percentage of participants achieving at least 90% improvement in site assessment F-VASI from baseline (F-VASI90). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
19. Percentage of Participants Achieving Local F-VASI100 at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    The site assessment of the F-VASI was calculated using a formula that included contribution from face (possible range, 0-4): Local F-VASI = [Digit Units] × [Depigmentation] × 0.1. Scalp, neck, eyebrows, eyelashes, and vermilion were excluded from this calculation. The volar surface of 1 digit (the participant's thumb) was approximately 0.1% of the total body surface area and was used as a guide to estimate the baseline percentage of vitiligo involvement of face. The extent of depigmentation was expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. Percent change from baseline in Local F-VASI = ((post baseline Local F-VASI - baseline Local F-VASI)/baseline Local F-VASI)×100. This outcome measure was the percentage of participants achieving 100% improvement in site assessment F-VASI from baseline (F-VASI100). Negative percent change from baseline in F-VASI signified an improvement. Baseline was defined as the last measurement prior to first dosing (Day 1).
20. Change From Baseline in Total VitiQoL Score at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 16 and 24 ]

    The Vitiligo-Specific Quality of Life (VitiQoL) instrument was a reliable and validated vitiligo disease-specific health-related quality of life (HRQoL) instrument which measured concepts relevant to vitiligo participants. The VitiQoL was a 15-item PRO measure which measured concepts of symptoms, daily activities, leisure activities, work, personal relationships and treatment. Responses ranged from "not at all" (scored 0) to "most of the time" (scored 6) and gave a minimum and maximum score from 0 to 90, with higher scores representing greater burden. The VitiQoL total score was calculated as sum of items 1-15.

    The change from baseline in total VitiQoL score was analyzed using the mixed-effect models repeated measures (MMRM) analysis. Baseline was defined as the last measurement prior to first dosing (Day 1).

21. Change From Baseline in VitiQoL Participation Limitation Domain Score at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 16 and 24 ]

    The VitiQoL was a reliable and validated vitiligo disease specific HRQoL instrument which measured concepts relevant to vitiligo participants. The VitiQoL was a 15-item PRO measure which measured concepts of symptoms, daily activities, leisure activities, work, personal relationships and treatment. Responses ranged from "not at all" (scored 0) to "most of the time" (scored 6) and gave a minimum and maximum score from 0 to 90, with higher scores representing greater burden. The VitiQoL Participation Limitation domain score was the sum of items 3, 4, 6, 9, 10, 11, 14 and ranged from 0 to 42.

    The change from baseline in VitiQoL Participation Limitation Domain Score was analyzed using the MMRM analysis. Baseline was defined as the last measurement prior to first dosing (Day 1).

22. Change From Baseline in VitiQoL Stigma Domain Score at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 16 and 24 ]

    The VitiQoL was a reliable and validated vitiligo disease specific HRQoL instrument which measured concepts relevant to vitiligo participants. The VitiQoL was a 15-item PRO measure which measured concepts of symptoms, daily activities, leisure activities, work, personal relationships and treatment. Responses ranged from "not at all" (scored 0) to "most of the time" (scored 6) and gave a minimum and maximum score from 0 to 90, with higher scores representing greater burden. The VitiQoL Stigma domain score was the sum of items 1, 2, 5, 7 and 15, and ranged from 0 to 30.

    The change from baseline in VitiQoL Stigma Domain Score was analyzed using the MMRM analysis. Baseline was defined as the last measurement prior to first dosing (Day 1).

23. Change From Baseline in VitiQoL Behaviors Domain Score at Designated Time Points - DR Period [ Time Frame: Baseline, Weeks 4, 16 and 24 ]

    The VitiQoL was a reliable and validated vitiligo disease specific HRQoL instrument which measured concepts relevant to vitiligo participants. The VitiQoL was a 15-item PRO measure which measured concepts of symptoms, daily activities, leisure activities, work, personal relationships and treatment. Responses ranged from "not at all" (scored 0) to "most of the time" (scored 6) and gave a minimum and maximum score from 0 to 90, with higher scores representing greater burden. The VitiQoL Behaviors domain score was the sum of items 8, 12 and 13, and ranged from 0 to 18.

    The change from baseline in VitiQoL Behaviors Domain Score was analyzed using the MMRM analysis. Baseline was defined as the last measurement prior to first dosing (Day 1).

24. Percentage of Participants Achieving sIGA 0 or 1 and at Least a 2-Point Improvement at Week 24 - DR Period [ Time Frame: Week 24 ]

    The percentage of participants achieving a static Investigator Global Assessment (sIGA) Score 0/1 and sIGA ≥2-point improvement at Week 24 was presented in this outcome measure. The sIGA score ranged from 0 to 4.

    The sIGA Score 0 represented "Clear" with no signs of loss of pigmentation with natural light or with Woods lamp examination.

    The sIGA Score 1 represented "Almost Clear" with the following descriptors:

    • Faint, barely detectable loss of pigmentation mainly located on dorsal hands, feet, bony prominences, and/or limited areas.
    • Approximately 90% pigmentation within lesions.
    • No or rare signs of Koebner phenomenon, confetti like or trichrome lesions could be present.

    The sIGA Scores 2, 3 and 4 represented "Mild Vitiligo", "Moderate Vitiligo" and "Severe Vitiligo", respectively.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female subjects between 18-65 years of age, inclusive, at time of informed consent.
• Must have moderate to severe active non-segmental vitiligo.

Exclusion Criteria:

• History of human immunodeficiency virus (HIV) or positive HIV serology at screening,
• Infected with hepatitis B or hepatitis C viruses.
• Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Contacts and Locations

Locations

United States, California

Marvel Research, LLC

Huntington Beach, California, United States, 92647

University of California, Irvine, Dermatology Clinical Research Center

Irvine, California, United States, 92697

Vitiligo and Pigmentation Institute Of Southern California

Los Angeles, California, United States, 90036

Dermatology Specialist, Inc.

Murrieta, California, United States, 92562

Dermatology Specialists, Inc.

Oceanside, California, United States, 92056

UC Davis Health

Sacramento, California, United States, 95816

United States, Connecticut

Brookside Dermatology Associates

Bridgeport, Connecticut, United States, 06606

New England Research Associates, LLC

Bridgeport, Connecticut, United States, 06606

United States, Florida

New Horizon Research Center

Miami, Florida, United States, 33165

Park Avenue Dermatology

Orange Park, Florida, United States, 32073

ForCare Clinical Research

Tampa, Florida, United States, 33613

United States, Illinois

Advanced Skin and MOHS Surgery Center, c/o TrialSpark, Inc.

Chicago, Illinois, United States, 60657

United States, Maryland

Chevy Chase Dermatology Center (TrialSpark, Inc.)

Chevy Chase, Maryland, United States, 20815

TrialSpark - Samantha Toerge, MD

Chevy Chase, Maryland, United States, 20815

TrialSpark - Ronald Shore, MD

Rockville, Maryland, United States, 20852

United States, Massachusetts

Tobias & Battite, Inc.

Boston, Massachusetts, United States, 02111

Tufts Medical Center

Boston, Massachusetts, United States, 02111

UMass Memorial Medical Center, Hahnemann Campus

Worcester, Massachusetts, United States, 01605

Investigational Drug Service Pharmacy

Worcester, Massachusetts, United States, 01655

UMass Memorial Medical Center Ear Nose and Throat

Worcester, Massachusetts, United States, 01655

University of Massachusetts Medical School

Worcester, Massachusetts, United States, 01655

United States, Michigan

Henry Ford Hospital Department of Dermatology

Detroit, Michigan, United States, 48202

United States, Minnesota

University of Minnesota Department of Dermatology

Minneapolis, Minnesota, United States, 55455

United States, New Jersey

The Dermatology Group, P.C.

Verona, New Jersey, United States, 07044

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10003

Upper West Side Dermatology c/o TrialSpark, Inc

New York, New York, United States, 10023

MDCS: Medical Dermatology & Cosmetic Surgery (TrialSpark, Inc.)

New York, New York, United States, 10065

South Nassau Dermatology

Oceanside, New York, United States, 11572

TrialSpark, Inc. - Russell W. Cohen, MD

Oceanside, New York, United States, 11572

United States, North Carolina

PMG Research of Wilmington, LLC

Wilmington, North Carolina, United States, 28411

United States, Ohio

Remington-Davis, Inc. Clinical Research

Columbus, Ohio, United States, 43215

ForeFront Dermatology

Columbus, Ohio, United States, 43220

United States, Oklahoma

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, United States, 74136

United States, Texas

University Physicians Group

Austin, Texas, United States, 78701

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390-9191

Pickens Academic Tower

Houston, Texas, United States, 77030

The University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Virginia

Virginia Clinical Research, Inc

Norfolk, Virginia, United States, 23502

Tamjidi Skin Institute (TrialSpark, Inc.)

Vienna, Virginia, United States, 22182

Australia, New South Wales

The Skin Hospital

Darlinghurst, New South Wales, Australia, 2010

Premier Specialists Pty Ltd

Kogarah, New South Wales, Australia, 2217

Australia, Queensland

Veracity Clinical Research Pty Ltd

Woolloongabba, Queensland, Australia, 4102

Australia, Victoria

Skin Health Institute

Carlton, Victoria, Australia, 3053

Sinclair Dermatology

East Melbourne, Victoria, Australia, 3002

The Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

The Royal Melbourne Hospital

Parkville, Victoria, Australia, 3052

Belgium

Hôpital Erasme Dermatology

Brussels, Belgium, 1070

UZ Brussel - Dermatology

Brussel, Belgium, 1090

UZ Gent - Dermatology

Gent, Belgium, 9000

Canada, British Columbia

Dr. Chih-ho Hong Medical Inc.

Surrey, British Columbia, Canada, V3R 6A7

Enverus Medical Research

Surrey, British Columbia, Canada, V3V 0C6

University of British Columbia

Vancouver, British Columbia, Canada, V5Z 4E8

Canada, Manitoba

Wiseman Dermatology Research Inc.

Winnipeg, Manitoba, Canada, R3M 3Z4

Canada, Ontario

CCA Medical Research

Ajax, Ontario, Canada, L1S 7K8

Guenther Research Inc.

London, Ontario, Canada, N6A 3H7

Lynderm Research Inc.

Markham, Ontario, Canada, L3P 1X3

DermEdge Research

Mississauga, Ontario, Canada, L5H 1G9

North York Research Inc.

North York, Ontario, Canada, M2M 4J5

The Centre for Clinical Trials

Oakville, Ontario, Canada, L6J 7W5

The Centre for Dermatology

Richmond Hill, Ontario, Canada, L4B 1A5

K.Papp Clinical Research

Waterloo, Ontario, Canada, N2J 1C4

Canada, Quebec

Innovaderm Research Inc.

Montreal, Quebec, Canada, H2X 2V1

Diex Research Sherbrooke Inc.

Sherbrooke, Quebec, Canada, J1L 0H8

Canada

Centre de Recherche Dermatologique du Quebec metropolitain (CRDQ)

Quebec, Canada, G1V 4X7

Centre de Recherche Saint-Louis

Quebec, Canada, G1W 4R4

Centre de Recherche Saint-Louis

Quebec, Canada, G1W1S2

Germany

Fachklinik Bad Bentheim, Fachbereich Dermatologie und Allergologie, Dermatologische Ambulanz

Bad Bentheim, Germany, 48455

Universitaetsklinikum Erlangen Hautklinik Studienambulanz

Erlangen, Germany, 91054

Universitätsklinikum Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie

Frankfurt am Main, Germany, 60590

Universitaetsklinikum Schleswig-Holstein, Campus Luebeck CCIM

Luebeck, Germany, 23538

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Germany, 55131

Universitaetsklinikum Muenster

Muenster, Germany, 48149

Italy

Istituti Fisioterapici Ospitalieri, Istituto di Ricovero e Cura a Carattere Scientifico,

Roma, RM, Italy, 00144

Japan

Nagoya City University Hospital - Dermatology

Nagoya, Aichi, Japan, 467-8602

Tohoku University Hospital

Sendai, Miyagi, Japan, 980-8574

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, Japan, 113-8603

Tokyo Medical University Hospital

Shinjuku-ku, Tokyo, Japan, 160-0023

Yamanashi Prefectural Central Hospital

Kofu, Yamanashi, Japan, 400-8506

Korea, Republic of

Dongguk University Ilsan Hospital

Goyang-si, Gyeonggi-do, Korea, Republic of, 10326

The Catholic University of Korea, St. Vincent's Hospital

Suwon-si, Gyeonggi-do, Korea, Republic of, 16247

Ajou University Hospital

Suwon, Gyeonggi-do, Korea, Republic of, 16499

Inha University Hospital

Incheon, Korea, Republic of, 22332

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08041

Hospital Universitario Reina Sofia

Cordoba, Spain, 14004

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitari i Politecnic La Fe

Valencia, Spain, 46026

Taiwan

Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital

Kaohsiung, Taiwan, 83301

National Cheng Kung University Hospital

Tainan, Taiwan, 70403

National Taiwan University Hospital

Taipei, Taiwan, 10002

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] June 26, 2020

Statistical Analysis Plan  [PDF] February 25, 2021

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ezzedine K, Peeva E, Yamaguchi Y, Cox LA, Banerjee A, Han G, Hamzavi I, Ganesan AK, Picardo M, Thaci D, Harris JE, Bae JM, Tsukamoto K, Sinclair R, Pandya AG, Sloan A, Yu D, Gandhi K, Vincent MS, King B. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial. J Am Acad Dermatol. 2023 Feb;88(2):395-403. doi: 10.1016/j.jaad.2022.11.005. Epub 2022 Nov 9. Erratum In: J Am Acad Dermatol. 2023 Sep;89(3):639.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03715829
• Other Study ID Numbers: B7981019; 2018-001271-20 ( EudraCT Number )
• First Posted: October 23, 2018
• Results First Posted: March 25, 2022
• Last Update Posted: March 25, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Vitiligo; Hypopigmentation; Pigmentation Disorders; Skin Diseases; PF-06700841; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action