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

• Abrocitinib 100 mg (Drug): In the initial treatment period, Abrocitinib 100 mg, administered as two tablets to be taken orally once daily.
• Abrocitinib 200 mg (Drug): In the initial treatment period, Abrocitinib 200 mg, administered as two tablets to be taken orally once daily.
• Placebo (Drug): 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.
• Abrocitinib 100 mg (Drug): 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.
• Abrocitinib 100 mg (Drug): In the secondary treatment period, Abrocitinib 100 mg, administered as one tablet to be taken orally once daily.
• Abrocitinib 200 mg (Drug): In the secondary treatment period, Abrocitinib 200 mg, administered as two tablets to be taken orally once daily.

Primary outcomes

• 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]: The incidence of treatment emergent adverse events
• 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]: The incidence of serious adverse events and adverse events leading to discontinuation
• 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 clinical laboratory values
• 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 electrocardiogram (ECG) measurements
• 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]: Change from baseline in vital signs

Secondary outcomes

• Investigator's Global Assessment (IGA) [Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92]: 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
• Eczema Area and Severity Index (EASI) [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]: 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
• Pruritus Numerical Rating Scale (NRS) [Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92]: 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
• Patient Global Assessment (PtGA) [Baseline, Week 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92]: Change from baseline of PtGA at all scheduled time points
• Body Surface Area (BSA) affected [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 the percentage BSA affected at all scheduled time points
• Dermatology Life Quality Index (DLQI) or Children's DLQI (CDLQI) [Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92]: Change from baseline in DLQI or CDLQI at all scheduled time points
• Patient Oriented Eczema Measure (POEM) [Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92]: Change from baseline in POEM at all scheduled time points
• Hospital Anxiety and Depression Scale (HADS) [Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 64, Week 72, Week 84, Week 92, Week 96]: Change from baseline in HADS at all scheduled time points
• EuroQol Quality of Life 5 Dimension 5 Level Scale (EQ-5D-5L) or EuroQol Quality of Life 5 Dimension Youth Scale (EQ-5D-Y) [Baseline, Week 24, Week 48, Week 60, Week 72, Week 92]: Change from baseline of EQ-5D-5L or EQ-5D-Y at all scheduled time points
• Steroid-Free Days [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]: Number of steroid-free days will be assessed throughout the duration of the study.
• Serum Hs-CRP Levels [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 at all scheduled time points
• Change in height standard deviation score (SDS) [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) at all scheduled time points
• 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]: Proportion of abnormal findings in knee MRI in adolescent subjects exposed to abrocitinib 100mg and 200mg QD

Sex: All, ages: 12 Years to any

Inclusion Criteria:

1. 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.
2. 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.
3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
4. 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.
5. 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:

   1. Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to allocation to treatment.
   2. 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:

1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
2. Have medically confirmed ovarian failure; or
3. 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
   1. 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.
   2. 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.
   3. 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.
   4. Ongoing adverse event in the qualifying Parent study which in the opinion of the investigator, or sponsor, is an ongoing safety concern.
   5. 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.

439 more sites not listed.

• Results publication: Pink AE, Rice ZP, Gooderham MJ, Wang F, Wollenberg A, Biswas P, Chan G, Alderfer J, Watkins M. Does Baseline Severity of Atopic Dermatitis Impact the Long-Term Efficacy of Abrocitinib? Post-hoc Analysis of Two Randomized Trials. Dermatol Ther (Heidelb). 2026 Oct 8. doi: 10.1007/s13555-026-01937-1. Online ahead of print. PMID 42844558
• Results publication: Weidinger S, Reich K, Issa N, Hong HC, Bunick CG, Biswas P, Chan G, Guler E, Watkins M, Alderfer J. Abrocitinib Achieves Early and Complete/Near-Complete Skin Clearance Plus Itch-Free State in Atopic Dermatitis: Phase 3 Pooled Post Hoc Analysis. Dermatol Ther (Heidelb). 2026 Aug;16(8):4217-4225. doi: 10.1007/s13555-026-01833-8. Epub 2026 Jun 27. PMID 42365219
• Results publication: Silverberg JI, Simpson EL, Farooqui SA, Chan G, Biswas P, Guler E. Efficacy and Safety of Variable-Dose Versus Continuous-Dose Abrocitinib Treatment in Patients with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis. Dermatol Ther (Heidelb). 2026 May 20. doi: 10.1007/s13555-026-01778-y. Online ahead of print. PMID 42162528
• Results publication: Paller AS, Eichenfield LF, Irvine AD, Flohr C, Wollenberg A, Barbarot S, Bangert C, Spergel JM, Selfridge A, Biswas P, Fan H, Alderfer J, Watkins M, Koppensteiner H. Integrated Efficacy and Safety Analysis of Abrocitinib in Adolescents With Moderate-to-Severe Atopic Dermatitis. Allergy. 2025 Aug;80(8):2213-2224. doi: 10.1111/all.16512. Epub 2025 Mar 3. PMID 40028832
• Results publication: Silverberg JI, Simpson EL, Pink AE, Weidinger S, Chan G, Biswas P, Clibborn C, Guler E. Switching from Dupilumab to Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of Efficacy After Treatment With Dupilumab in JADE DARE. Dermatol Ther (Heidelb). 2025 Feb;15(2):367-380. doi: 10.1007/s13555-024-01320-y. Epub 2025 Feb 4. PMID 39903335
• Results publication: Silverberg JI, Thyssen JP, Lazariciu I, Myers DE, Guler E, Chovatiya R. Abrocitinib may improve itch and quality of life in patients with itch-dominant atopic dermatitis. Skin Health Dis. 2024 May 5;4(4):e382. doi: 10.1002/ski2.382. eCollection 2024 Aug. PMID 39104653
• Results publication: Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, Egeberg A, Valdez H, Zhang M, Farooqui SA, Romero W, Thorpe AJ, Rojo R, Johnson S. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. Am J Clin Dermatol. 2021 Sep;22(5):693-707. doi: 10.1007/s40257-021-00618-3. Epub 2021 Aug 18. PMID 34406619

• Pfizer CT.gov Call Center, Study director, Pfizer

NIH grants: 2023