PF-06651600 for the Treatment of Alopecia Areata

Study Overview
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Brief Summary
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This is a global Phase 2b/3 study to evaluate the safety and effectiveness of an investigational study drug (called PF-06651600) in adults and adolescents (12 years and older) who have 50% or greater scalp hair loss. The study is placebo-controlled, meaning that some patients entering the study will not receive active study drug but will receive tablets with no active ingredients (a placebo). This is a dose-ranging study, investigating 5 different dosing regimens. It will be double-blinded, meaning that the sponsor, the study doctors, the staff, and the patients will not know whether a patient is on active study drug (or the dose) or placebo.

Official Title
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A PHASE 2B/3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF PF-06651600 IN ADULT AND ADOLESCENT ALOPECIA AREATA (AA) SUBJECTS WITH 50% OR GREATER SCALP HAIR LOSS

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: PF-06651600 Induction Dose
* Drug: PF-06651600 Maintenance Dose #1
* Drug: PF-06651600 Maintenance Dose #2
* Drug: PF-06651600 Maintenance Dose #3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of alopecia areata with no other cause of hair loss ≥50% hair loss of the scalp, including alopecia totalis and alopecia universalis, without evidence of terminal hair regrowth within 6 months Current episode of hair loss ≤10 years Exclusion Criteria: Other types of alopecia or other diseases that can cause hair loss Other scalp diseases that could interfere with assessment of hair loss/regrowth Subjects with shaved heads must not enter the study until hair has grown back & is considered stable by the investigator Any previous use of any Janus kinase (JAK) inhibitor

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A<br>Induction dose given once daily (QD) for 4 weeks followed by maintenance dose #1 given QD for 44 weeks | Drug: PF-06651600 Induction Dose<br>* Oral tablets taken once daily (QD)<br>Drug: PF-06651600 Maintenance Dose #1<br>* Oral tablets taken QD<br>|
| Experimental: Sequence B<br>Induction dose given QD for 4 weeks followed by maintenance dose #2 given QD for 44 weeks | Drug: PF-06651600 Induction Dose<br>* Oral tablets taken once daily (QD)<br>Drug: PF-06651600 Maintenance Dose #2<br>* Oral tablets taken QD<br>|
| Experimental: Sequence C<br>Maintenance dose #1 given QD for 48 weeks | Drug: PF-06651600 Maintenance Dose #1<br>* Oral tablets taken QD<br>|
| Experimental: Sequence D<br>Maintenance dose #2 given QD for 48 weeks | Drug: PF-06651600 Maintenance Dose #2<br>* Oral tablets taken QD<br>|
| Experimental: Sequence E<br>Maintenance dose #3 given QD for 48 weeks | Drug: PF-06651600 Maintenance Dose #3<br>* Oral tablets taken QD<br>|
| Experimental: Sequence F<br>Placebo given QD for 24 weeks followed by induction dose given QD for 4 weeks then maintenance dose #1 given QD for 20 weeks | Drug: PF-06651600 Induction Dose<br>* Oral tablets taken once daily (QD)<br>Drug: PF-06651600 Maintenance Dose #1<br>* Oral tablets taken QD<br>Drug: Placebo<br>* Oral tablets taken QD<br>|
| Experimental: Sequence G<br>Placebo given QD for 24 weeks followed by maintenance dose #1 given QD for 24 weeks | Drug: PF-06651600 Maintenance Dose #1<br>* Oral tablets taken QD<br>Drug: Placebo<br>* Oral tablets taken QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Absolute Severity of Alopecia Tool (SALT) Score of Less Than or Equal to 20 at Week 24 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score less than or equal to (<=) 20 at week 24 were reported. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 24: Analysis 4 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <= 10 at week 24 were reported. | Week 24 | 
| Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 24: Analysis 1 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <= 10 at week 24 were reported. | Week 24 | 
| Percentage of Participants With Patient Global Impression of Change (PGI-C) Score of Moderately Improved or Greatly Improved at Week 24 | PGI-C is a self-administered questionnaire to evaluate the improvement or worsening of participant's AA as compared to the start of the study. PGI-C was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGI-C scores as follows: 1=greatly improved, 2=moderately improved, 3=slightly improved, 4=not changed, 5=slightly worsened, 6=moderately worsened and 7=greatly worsened. | Week 24 | 
| Exposure Response of PF-06651600 on Regrowth of Lost Hair Based on Absolute SALT Score of Less Than or Equal to 20 at Week 24: Maximum Effect (Emax) Model | The exposure response of Ritlecitinib (PF-06651600) on the regrowth of scalp hair was characterized using a Bayesian three-parameter hyperbolic Emax model for the SALT score <=20 at Week 24 with an additional term for effect of loading dose. In Emax exposure-response model the response function was the log odds of the percentage of participants with response based on SALT <=20 at Week 24, which was fit on the logistic scale and then back-transformed to percentage. The effect of loading dose is included as fixed factor in the model. The variable that represents loading dose has values of 1 for groups 200/50 mg once daily and 200/30 mg once daily and of 0 for the remaining groups. SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. | Week 24 | 
| Exposure Response of PF-06651600 on Regrowth of Lost Hair Based on Absolute SALT Score of Less Than or Equal to 10 at Week 24: Maximum Effect (Emax) Model | The exposure response of Ritlecitinib (PF-06651600) on the regrowth of scalp hair was characterized using a Bayesian three-parameter hyperbolic Emax model for the SALT score <=10 at Week 24 with an additional term for effect of loading dose. In Emax exposure-response model the response function was the log odds of the percentage of participants with response based on SALT <=10 at Week 24, which was fit on the logistic scale and then back-transformed to percentage. The effect of loading dose is included as fixed factor in the model. The variable that represents loading dose has values of 1 for groups 200/50 mg once daily and 200/30 mg once daily and of 0 for the remaining groups. SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. | Week 24 | 
| Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 20 at Week 4, 8, 12, 18, 28, 34, 40, and 48 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. | Week 4, 8, 12, 18, 28, 34, 40, and 48 | 
| Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 4, 8, 12, 18, 28, 34, 40, and 48 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <=10 were reported. | Week 4, 8, 12, 18, 28, 34, 40, and 48 | 
| Percentage of Participants With at Least 75% Improvement in SALT Score (SALT75) From Baseline at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. A SALT 75 response was a 75% or greater reduction from baseline in SALT score. | Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | 
| Change From Baseline in SALT Score at Week 4, 8, 12, 18, and 24 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. Baseline was defined as pre-dose on Day 1. | Baseline (Day 1), Week 4, 8, 12, 18, and 24 | 
| Change From Baseline in SALT Score at Week 28, 34, 40, and 48 | SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. Baseline was defined as pre-dose on Day 1. | Baseline (Day 1), Week 28, 34, 40, and 48 | 
| Percentage of Participants With at Least a 2 Grade Improvement From Baseline or a Score of 3 in Eyebrow Assessment (EBA) Score (Among Participants Without Normal EBA at Baseline) at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | EBA is a numeric rating scale developed to characterize eyebrow hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal), where, 0= no eyebrow, 1=minimal eyebrow, 2=moderate eyebrow and 3= normal eyebrow, where higher scores represent less hair loss of eyebrows. | Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | 
| Percentage of Participants With at Least a 2 Grade Improvement From Baseline or a Score of 3 in Eyelash Assessment (ELA) Score (Among Participants Without Normal ELA at Baseline) at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | ELA is a numeric rating scale developed to characterize eyelash hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal), where, 0=no eyelash, 1=minimal eyelash, 2=moderate eyelash and 3=normal eyelash, where higher scores represent less hair loss of eyelash. | Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 | 
| Percentage of Participants With Patient Global Impression of Change (PGI-C) Score of Moderately Improved or Greatly Improved at Week 4, 8, 12, 18, 24, 34, 40, and 48 | PGI-C is a self-administered questionnaire to evaluate the improvement or worsening of participant's AA as compared to the start of the study. PGI-C was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGI-C scores as follows: 1=greatly improved, 2=moderately improved, 3=slightly improved, 4=not changed, 5=slightly worsened, 6=moderately worsened and 7=greatly worsened. | Week 4, 8, 12, 18, 24, 34, 40, and 48 | 
| Change From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Week 4, 8, 12, 18, and 24: Emotional Symptoms and Activity Limitations | AAPPO scale is 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over past week. Items 1-4 assessed current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss'. Items 5-8 assessed emotional symptoms. Response choices on these items were scored from 0 ='never' to 4='always'. Items 9-11 assessed activity limitations. Response choices on these items were scored from 0='not at all' to 4='completely'. Change from baseline in AAPPO emotional symptoms sub score were calculated as mean of items 5-8 and ranged from 0(never) to 4(always), where higher scores indicated more emotional symptoms. Change from baseline in AAPPO activity limitations sub score was calculated as mean of items 9-11 and ranged from 0(not at all) to 4(completely), where higher scores indicated more activity limitations. Baseline was defined as pre-dose on Day 1. | Baseline (Day 1), Week 4, 8, 12, 18, and 24 | 
| Change From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Week 34, 40, and 48: Emotional Symptoms and Activity Limitations | AAPPO scale is 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over past week. Items 1-4 assessed current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss'. Items 5-8 assessed emotional symptoms. Response choices on these items were scored from 0 ='never' to 4='always'. Items 9-11 assessed activity limitations. Response choices on these items were scored from 0='not at all' to 4='completely'. Change from baseline in AAPPO emotional symptoms sub score were calculated as mean of items 5-8 and ranged from 0(never) to 4(always), where higher scores indicated more emotional symptoms. Change from baseline in AAPPO activity limitations sub score was calculated as mean of items 9-11 and ranged from 0(not at all) to 4(completely), where higher scores indicated more activity limitations. Baseline was defined as pre-dose on Day 1. | Baseline (Day 1), Week 34, 40, and 48 | 
| Percentage of Participants With Improvement From Baseline on Alopecia Areata Patient Priority Outcomes (AAPPO) Items 1-4 at Week 4, 8, 12, 18, 24, 34, 40, and 48 | AAPPO scale is a 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over the past week. Items 1-4 were to assess the current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on a scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss', where higher scores indicated more hair loss. | Week 4, 8, 12, 18, 24, 34, 40, and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alopecia, Alopecia totalis, Alopecia universalis, Patchy hair loss, Diffuse hair loss, Hair loss, Hair disease, PF-06651600, Ritlecitinib