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

Tracking Information

• First Submitted Date: October 19, 2018
• First Posted Date: October 23, 2018
• Results First Submitted Date: January 10, 2022
• Results First Posted Date: March 25, 2022
• Last Update Posted Date: March 25, 2022
• Actual Study Start Date: November 26, 2018
• Actual Primary Completion Date: February 5, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2022)

• 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.
• 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.
• 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).
• 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).
• 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.
• 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.
• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: October 19, 2018)

• Percent change from baseline of vitiligo area scoring index (VASI) at Week 24. [ Time Frame: baseline, 24 weeks ]
  assessment of overall vitiligo to measure efficacy of PF-06651600
• Number of treatment emergent adverse events (TEAEs) [ Time Frame: baseline up to end of study (56 weeks) ]
• Number of subjects with change from baseline in laboratory tests results [ Time Frame: baseline to end of study (56 weeks) ]
• Number of subjects reporting TEAEs [ Time Frame: baseline up to end of study (56 weeks) ]
• Number of specific clinical laboratory abnormalities [ Time Frame: baseline to end of study (56 weeks) ]
• Number of treatment emergent serious adverse events (TESAEs) [ Time Frame: baseline to end of study (56 weeks) ]
• number of subjects who experienced TESAEs [ Time Frame: baseline to end of study (56 weeks) ]

Current Secondary Outcome Measures (submitted: March 1, 2022)

• 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.
• 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).
• 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).
• 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.
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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.
• 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.
• 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.
• 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.
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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.

Original Secondary Outcome Measures (submitted: October 19, 2018)

• Percentage of subjects achieving at least 50% improvement in VASI from baseline (VASI50) at Week 24. [ Time Frame: 24 weeks ]
• Percent change from baseline in VASI [ Time Frame: baseline to week 20 ]
• Percent change from baseline in facial VASI [ Time Frame: baseline to week 24 ]
• Percent change from baseline in vitiligo extent score (VES) [ Time Frame: baseline to week 24 ]
• Percent change from baseline in self assessment vitiligo extent score (SA-VES) [ Time Frame: baseline to week 24 ]
• Absolute change from baseline in VASI [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving VASI50 [ Time Frame: baseline to week 20 ]
• Percentage of subjects achieving at least 75% improvement in VASI from baseline (VASI75) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 90% improvement in VASI from baseline (VASI90) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 100% improvement in VASI from baseline (VASI100) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving facial VASI50 [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving facial VASI75 [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving facial VASI90 [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving facial VASI100 [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 50% improvement in VES (VES50) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 75% improvement in VES (VES75) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 90% improvement in VES (VES90) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving at least 100% improvement in VES (VES100) [ Time Frame: baseline to week 24 ]
• Change from baseline in vitiligo specific quality of life (VitiQoL) [ Time Frame: baseline to week 24 ]
• Percentage of subjects achieving a static investigator global assessment (sIGA) 0 or 1 and 2 point or greater improvement [ Time Frame: week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2b Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Active Non-segmental Vitiligo Subjects
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Active Non-segmental Vitiligo

Intervention

• Drug: PF-06651600
  Induction dose 1. Oral tablet taken QD
• Drug: PF-06651600
  Induction dose 2. Oral tablet taken QD
• Drug: PF-06651600
  Maintenance dose A. Oral tablet taken QD
• Drug: PF-06651600
  Maintenance Dose B. Oral tablet taken QD
• Drug: PF-06651600
  Maintenance Dose C. Oral tablet taken QD
• Drug: placebo
  placebo
• Drug: PF06700841
  Oral tablet taken QD
• Device: narrow-band UVB phototherapy
  Phototherapy will be combined with PF-06651600

Study Arms

• Experimental: Cohort 1
  Induction dose 1 given once a day(QD) for 4 weeks followed by maintenance dose A given QD for 20 weeks
  Interventions:

  • Drug: PF-06651600
  • Drug: PF-06651600
• Experimental: Cohort 2
  Induction dose 2 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks
  Interventions:

  • Drug: PF-06651600
  • Drug: PF-06651600
• Experimental: Cohort 3
  Maintenance dose A given QD for 24 weeks
  Intervention: Drug: PF-06651600
• Experimental: Cohort 4
  Maintenance dose B given QD for 24 weeks
  Intervention: Drug: PF-06651600
• Experimental: Cohort 5
  Maintenance dose C given QD for 24 weeks
  Intervention: Drug: PF-06651600
• Placebo Comparator: Cohort 6
  Placebo given QD for 24 weeks
  Intervention: Drug: placebo
• Experimental: Extension Cohort 1
  4 week drug holiday (no drug given) followed by PF-06700841 oral tablet QD for 20 weeks
  Intervention: Drug: PF06700841
• 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
  Interventions:

  • Drug: PF-06651600
  • Drug: PF-06651600
  • Device: narrow-band UVB phototherapy
• Experimental: Extension Cohort 3
  Induction dose 1 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks
  Interventions:

  • Drug: PF-06651600
  • Drug: PF-06651600
• Experimental: Extension Cohort 4
  Maintenance dose A given QD for 24 weeks
  Intervention: Drug: PF-06651600
• Experimental: Extension Cohort 5
  Maintenance dose B given QD for 24 weeks
  Intervention: Drug: PF-06651600
• No Intervention: Extension Cohort 6
  Observation period for 24 weeks

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 4, 2020): 366
• Original Estimated Enrollment (submitted: October 19, 2018): 330
• Actual Study Completion Date: February 5, 2021
• Actual Primary Completion Date: February 5, 2021 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Germany, Italy, Japan, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03715829
• Other Study ID Numbers: B7981019; 2018-001271-20 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: March 2022