Long-Term 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 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 alopecia areata. Eligible patients from the prior studies B7931005 (NCT02974868) and B7981015 (NCT03732807) will have an opportunity to enroll as well as patients who have not previously participated in either of these studies. The study is open-label and all patients entering the study will receive active study drug. A sub-study of approximately 60 adult patients who are participating in the B7981032 study will be conducted at select sites in the US, Australia and Canada. The sub-study will evaluate the immune response to tetanus and meningococcal vaccines in patients who have received a minimum of 6 months of 50 mg PF-06651600.

Official Title
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A PHASE 3 OPEN-LABEL, MULTI-CENTER, LONG-TERM STUDY INVESTIGATING THE SAFETY AND EFFICACY OF PF-06651600 IN ADULT AND ADOLESCENT PARTICIPANTS WITH ALOPECIA AREATA

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: PF-06651600
* Biological: Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine
* Biological: Meningococcal (groups A, C, W-135 and Y [ACWY]) oligosaccharide diphtheria CRM197 conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria- For de novo participants and participants from Study B7931005 and B7981015 with >30 days between first visit in B7981032 and last dose in the prior study: Clinical diagnosis of alopecia areata (AA) with no other cause of hair loss. Androgenetic alopecia coexistent with AA is allowed. De novo participants >=12 to <18 years of age: >=50% terminal hair loss of the scalp due to AA, including alopecia totalis and alopecia universalis De novo participants >=18 years of age and participants from Study B7931005 or B7981015 with >30 days between first visit in B7981032 and last dose in the prior study: >=25% terminal hair loss of the scalp due to AA, including alopecia totalis and alopecia universalis No evidence of terminal scalp hair regrowth within 6 months (de novo only) Current episode of terminal scalp hair loss <=10 years (de novo only) Exclusion Criteria- For de novo participants and participants from Study B7931005 and B7981015 with >30 days between first visit in B7981032 and last dose in the prior study: Hearing loss with progression over previous 5 years, or sudden hearing loss, or middle or inner ear disease, or other auditory condition that is considered acute, fluctuating or progressive History of or current malignancies with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ History of a single episode of disseminated herpes zoster or disseminated herpes simplex, or a history of more than one episode of localized, dermatomal herpes zoster Infection requiring hospitalization, or parenteral antimicrobial therapy within 6 months prior to Day 1 Exclusion criteria for all participants: - Participants who have previously taken Janus kinase (JAK) inhibitors other than PF-06651600 must have received the last dose >12 weeks prior to the screening visit

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br>Participants who did not previously receive study intervention in either study B7931005 or B7981015 will receive 200 milligrams (mg) PF-06651600, given as four 50 mg tablets once daily (QD) for 1 month, followed by 50 mg PF-06651600 tablet or capsule given QD for 59 months. Patients participating in the vaccine sub-study will receive the 2 vaccines or one of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 9 visit and prior to or on the Month 56 visit of the main B7981032 study. | Drug: PF-06651600<br>* 50 mg oral tablets/capsules<br>Biological: Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine<br>* Single intramuscular injection administered to patients participating in the vaccine sub-study<br>Biological: Meningococcal (groups A, C, W-135 and Y [ACWY]) oligosaccharide diphtheria CRM197 conjugate vaccine<br>* Single intramuscular injection administered to patients participating in the vaccine sub-study<br>|
| Experimental: Treatment sequence 2<br>Participants who previously received study intervention in either study B7931005 or B7981015 will receive 50 mg PF-06651600 tablet or capsule given QD for 59 months. Patients participating in the vaccine sub-study will receive the 2 vaccines or 1 of the 2 vaccines at the vaccine sub-study Day 1, which will occur at a scheduled study visit on or after the Month 6 visit and prior to or on the Month 56 visit of the main B7981032 study. | Drug: PF-06651600<br>* 50 mg oral tablets/capsules<br>Biological: Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine<br>* Single intramuscular injection administered to patients participating in the vaccine sub-study<br>Biological: Meningococcal (groups A, C, W-135 and Y [ACWY]) oligosaccharide diphtheria CRM197 conjugate vaccine<br>* Single intramuscular injection administered to patients participating in the vaccine sub-study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects reporting treatment-emergent adverse events |  | Baseline through Month 36 | 
| Number of subjects reporting serious adverse events |  | Baseline through Month 36 | 
| Number of subjects reporting adverse events leading to discontinuation |  | Baseline through Month 36 | 
| Number of subjects with clinically significant abnormalities in vital signs |  | Baseline through Month 36 | 
| Number of subjects with clinically significant abnormalities in clinical laboratory values |  | Baseline through Month 36 | 
| Vaccine sub-study: Percentage of subjects with a tetanus booster response | Tetanus booster response is defined as 1) ≥4 fold rise in anti-tetanus toxoid IgG antibody concentration at Day 30 if the pre-vaccination concentration was ≤2.7 IU/mL; 2) ≥2 fold rise in anti tetanus toxoid IgG antibody if the pre-vaccination concentration was >2.7 IU/mL | Vaccine sub-study Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with an absolute Severity of Alopecia Tool (SALT) Score <=10 | SALT is a quantitative assessment of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss). | Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, and 36 | 
| Percentage of subjects with an absolute Severity of Alopecia Tool (SALT) Score <=20 | SALT is a quantitative assessment of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss). | Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, and 36 | 
| Change from baseline in SALT score | SALT is a quantitative assessment of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss). | Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, and 36 | 
| Percentage of subjects with a 75% improvement in SALT score from baseline | SALT is a quantitative assessment of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss). | Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, and 36 | 
| Percentage of subjects with at least a 2 grade improvement or a score of 3 in Eyebrow Assessment (EBA) score | EBA is a numeric rating scale developed to characterize eyebrow hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal). | Months 1, 3, 6, 12, 18, 24, and 36 | 
| Percentage of subjects with at least a 2 grade improvement or a score of 3 in Eyelash Assessment (ELA) score | ELA is a numeric rating scale developed to characterize eyelash hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal). | Months 1, 3, 6, 12, 18, 24, and 36 | 
| Patient's Global Impression of Change (PGI-C) response, defined as PGI-C score of moderately improved or greatly improved | PGI-C is a self administered questionnaire evaluating improvement or worsening of the participant's alopecia areata as compared to the start of the study and uses a single item, Since the start of the study, my alopecia areata has: …, with 7 responses ranging from greatly improved to greatly worsened. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Change from baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) domains | The AAPPO scale is a self administered questionnaire that measures the symptoms of AA as well as psychological and functional impacts over the past week. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Change from baseline in the depression subscale score of the Hospital Anxiety and Depression Scale (HADS) | HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety; HADS-D assesses state of lost interest and diminished pleasure response. Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Change from baseline in the anxiety subscale score of the Hospital Anxiety and Depression Scale (HADS) | HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety; HADS-D assesses state of lost interest and diminished pleasure response. Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Improvement on the Hospital Anxiety and Depression Scale (HADS) among participants with a baseline subscale score indicative of depression who achieved a normal subscale score indicative of an absence of depression | HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety; HADS-D assesses state of lost interest and diminished pleasure response. Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Improvement on the Hospital Anxiety and Depression Scale (HADS) among participants with a baseline subscale score indicative of anxiety who achieved a normal subscale score indicative of an absence of anxiety | HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety; HADS-D assesses state of lost interest and diminished pleasure response. Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Months 1, 3, 6, 9, 12, 18, 24, and 36 | 
| Vaccine sub-study: Percentage of subjects with a meningococcal serogroup C response | Meningococcal serogroup C response is defined as achieving ≥1:8 human serum bactericidal activity (hSBA) (in participants with undetectable pre-vaccination assay titers) | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Percentage of subjects with anti-tetanus antibody level ≥1.0 IU/mL |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Percentage of subjects with anti-tetanus antibody level ≥0.1 IU/mL |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Percentage of subjects with ≥4x increase in anti-tetanus antibody level from baseline |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Fold increase in anti-tetanus levels above baseline values |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Geometric mean concentrations (GMCs) of anti-tetanus antibody levels |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Percentage of subjects with ≥1:4 hSBA (in subjects with undetectable pre-vaccination assay titers) for meningococcal serogroup C |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Geometric mean titers (GMTs) of antibodies for meningococcal serogroup C |  | Vaccine sub-study Day 1 and Month 1 | 
| Number of subjects reporting treatment-emergent adverse events |  | Month 37 through Month 60 | 
| Number of subjects reporting serious adverse events |  | Month 37 through Month 60 | 
| Number of subjects reporting adverse events leading to discontinuation |  | Month 37 through Month 60 | 
| Number of subjects with clinically significant abnormalities in vital signs |  | Month 37 through Month 60 | 
| Number of subjects with clinically significant abnormalities in clinical laboratory values |  | Month 37 through Month 60 | 
| Vaccine sub-study: Number of subjects reporting serious adverse events |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Number of subjects reporting adverse events |  | Vaccine sub-study Month 1 | 
| Vaccine sub-study: Number of subjects reporting adverse events leading to discontinuation |  | Vaccine sub-study Month 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alopecia, Alopecia Areata, Alopecia totalis, Alopecia universalis, Hair loss, JAK inhibitor, PF-06651600, Ritlecitinib