Study to Evaluate Efficacy and Safety of PF-04965842 With or Without Topical Medications in Subjects Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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B7451015 is a Phase 3 study to evaluate Abrocitinib with or without Topical Medications in patients aged 12 years and older who have moderate to severe atopic dermatitis and have completed a qualifying parent study. The efficacy and safety of two dosage strengths of Abrocitinib, 100 mg and 200 mg taken orally once daily, will be evaluated over variable lengths of study participation. The study consists of a 92 week initial treatment period followed by a variable length secondary treatment period during which subjects will receive treatment with open-label abrocitinib until availability of commercial product in their country, or until the sponsor terminates the study in that country. The B7451015 study also includes a sub-study evaluating whether abrocitinib has any potential effects on adolescent bone with regard to abnormal bone findings in knee MRI. The sub-study will be conducted in selected countries at selected sites. Eligible subjects are those who were 12 to <18 years of age at the screening visit of the qualifying parent study and who are currently participating in the main B7451015 study. The sub-study will include serial Magnetic Resonance Imaging (MRI) annually and continue until all enrolled subjects are 18 years of age and have been imaged at least once or have discontinued/withdrawn.

Official Title
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A PHASE 3 MULTI-CENTER, LONG-TERM EXTENSION STUDY INVESTIGATING THE EFFICACY AND SAFETY OF ABROCITINIB, WITH OR WITHOUT TOPICAL MEDICATIONS, ADMINISTERED TO SUBJECTS AGED 12 YEARS AND OLDER WITH MODERATE TO SEVERE ATOPIC DERMATITIS

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: Abrocitinib 100 mg
* Drug: Abrocitinib 200 mg
* Drug: Placebo
* Drug: Abrocitinib 100 mg
* Drug: Abrocitinib 100 mg
* Drug: Abrocitinib 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the subject or their parent(s)/legal guardian, if applicable, have been informed of all pertinent aspects of the study. Male or female subjects of 12 years of age or older, at the time of informed consent and meets inclusion criterion for minimum body weight (if applicable) from qualifying Parent study. Adolescent subjects below the age of 18 years old (or country-specific age of majority) will only be enrolled in this study if instructed by the sponsor and approved by the country or regulatory/health authority. If these approvals have not been granted, only subjects aged 18 years (or country-specific age of majority) and older will be enrolled. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Must have completed the full treatment period of a qualifying Parent study OR must have completed the full rescue treatment period of a qualifying Parent study (if applicable) OR must have completed the full open-label run-in period in B7451014 and did not meet the protocol-specified response criteria at Week 12. Female subjects who are of childbearing potential (which includes all female subjects aged 12 years and older, regardless of whether they have experienced menarche) must ot be intending to become pregnant, currently pregnant, or lactating. The following onditions apply: Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to allocation to treatment. Female subjects of childbearing potential must agree to use a highly effective method of contraception (as per Section 4.4.1) for the duration of the active treatment period and for at least 28 days after the last dose of investigational product. For Czech Republic only, 5 b. is revised and 5 c. is added to require: Female subjects of childbearing potential 15 years of age who are at risk of pregnancy must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of investigational product. c. Female subjects less than 15 years of age must not be sexually active, and abstinence per the below definition should be confirmed prior to enrollment. NOTE: Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with the study treatments) may obviate the need for contraception ONLY if this is the preferred and usual lifestyle of the subject. 6. Female subjects of non-childbearing potential must meet at least 1 of the following criteria: Have undergone a documented hysterectomy and/or bilateral oophorectomy; Have medically confirmed ovarian failure; or Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential. 7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during the study. 8. Must agree to avoid use of prohibited medications throughout the duration of the study. Exclusion Criteria Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Currently have active forms of other inflammatory skin diseases, ie, not AD or have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis, Lupus) at the time of Day -1 that would interfere with evaluation of atopic dermatitis or response to treatment. Discontinued from treatment (or rescue treatment period/open-label run-in period, if applicable) early in a qualifying Parent study OR triggered a discontinuation criterion at any point during the qualifying Parent study which in the opinion of the investigator, or sponsor, is an ongoing safety concern. Ongoing adverse event in the qualifying Parent study which in the opinion of the investigator, or sponsor, is an ongoing safety concern. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study. There are also additional separate inclusion and exclusion criteria to assess eligibility specifically for the B7451015 MRI sub-study.

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: Abrocitinib 100 mg<br>Abrocitinib 100 mg QD PO | Drug: Abrocitinib 100 mg<br>* In the initial treatment period, Abrocitinib 100 mg, administered as two tablets to be taken orally once daily.<br>Drug: Placebo<br>* For subjects whose dose was changed from 100 mg Abrocitinib to placebo, one tablet will be administered to be taken orally once daily for the remainder of the study.<br>Drug: Abrocitinib 100 mg<br>* In the secondary treatment period, Abrocitinib 100 mg, administered as one tablet to be taken orally once daily.<br>|
| Experimental: Abrocitinib 200 mg<br>Abrocitinib 200 mg QD PO | Drug: Abrocitinib 200 mg<br>* In the initial treatment period, Abrocitinib 200 mg, administered as two tablets to be taken orally once daily.<br>Drug: Abrocitinib 100 mg<br>* For subjects whose dose was changed from 200 mg Abrocitinib to 100 mg PF-04965842, one tablet will be administered to be taken orally once daily for the remainder of the study.<br>Drug: Abrocitinib 200 mg<br>* In the secondary treatment period, Abrocitinib 200 mg, administered as two tablets to be taken orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events | The incidence of treatment emergent adverse events | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Serious adverse events and adverse events leading to discontinuation | The incidence of serious adverse events and adverse events leading to discontinuation | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Change from baseline in clinical laboratory values | Change from baseline in clinical laboratory values | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Change from baseline in electrocardiogram (ECG) measurements | Change from baseline in electrocardiogram (ECG) measurements | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Change from baseline in vital signs | Change from baseline in vital signs | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment (IGA) | Response based on the IGA score of clear (0) or almost clear (1) (on a 5 point scale) and a reduction from baseline of >=2 points at all scheduled time points | Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | 
| Eczema Area and Severity Index (EASI) | Response based on greater than or equal to 50%, 75% and 90% improvement from baseline in the EASI total score (EASI50, EASI75, and EASI90) at all scheduled time points | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Pruritus Numerical Rating Scale (NRS) | Response based on an improvement greater than or equal to 3 points and greater than or equal to 4 points from baseline in the pruritus NRS at all scheduled time points | Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | 
| Patient Global Assessment (PtGA) | Change from baseline of PtGA at all scheduled time points | Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | 
| Body Surface Area (BSA) affected | Change from baseline in the percentage BSA affected at all scheduled time points | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Dermatology Life Quality Index (DLQI) or Children's DLQI (CDLQI) | Change from baseline in DLQI or CDLQI at all scheduled time points | Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | 
| Patient Oriented Eczema Measure (POEM) | Change from baseline in POEM at all scheduled time points | Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | 
| Hospital Anxiety and Depression Scale (HADS) | Change from baseline in HADS at all scheduled time points | Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 64, Week 72, Week 84, Week 92, Week 96 | 
| EuroQol Quality of Life 5 Dimension 5 Level Scale (EQ-5D-5L) or EuroQol Quality of Life 5 Dimension Youth Scale (EQ-5D-Y) | Change from baseline of EQ-5D-5L or EQ-5D-Y at all scheduled time points | Baseline, Week 24, Week 48, Week 60, Week 72, Week 92 | 
| Steroid-Free Days | Number of steroid-free days will be assessed throughout the duration of the study. | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Serum Hs-CRP Levels | Serum Hs-CRP levels at all scheduled time points | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Change in height standard deviation score (SDS) | Change in height standard deviation score (SDS) at all scheduled time points | Throughout study regardless of availability of commercial product until at least 2024, or until the sponsor terminates the study; an estimated maximum of 8 years | 
| Proportion of abnormal findings in knee MRI in adolescent subjects exposed to abrocitinib 100mg and 200mg QD | Proportion of abnormal findings in knee MRI in adolescent subjects exposed to abrocitinib 100mg and 200mg QD | Throughout sub-study until all enrolled subjects are 18 years of age and have been imaged at least once or have discontinued or withdrawn; an estimated maximum of 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, atopic dermatitis, atopic eczema, eczema, JAK, janus kinase, Magnetic Resonance Imaging