Final Clinical Study Report
Protocol B7451013

CLINICAL STUDY REPORT SYNOPSIS
Sponsor: Pfizer, Inc.
Investigational Product: PF-04965842 (abrocitinib)
Clinical Study Report Synopsis: Protocol B7451013
Protocol Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group,
Multi-Center Study to Evaluate the Efficacy and Safety of PF-04965842 Monotherapy in
Subjects Aged 12 Years and Older, With Moderate to Severe Atopic Dermatitis
Investigators: Refer to Appendix 16.1.4.1 for a list of investigators involved in this study.
Study Center(s): A total of 391 subjects were randomized at 102 sites in 13 countries,
including sites in the United States (n=19), Poland (n=14), Republic of Korea (n=10), Japan(n=8), Australia (n=7), Bulgaria (n=7), Canada (n=7), Germany (n=7), United Kingdom(n=6), China (n=5), Latvia (n=5), Hungary (n=4), and Czech Republic (n=3). Refer toAppendix 16.1.4.1 for a list of sites involved in this study.
Publications Based on the Study: None
Study Initiation Date: First Subject First Visit (FSFV): 29 June 2018.
Study Completion Date: Last Subject Last Visit (LSLV): 13 August 2019.
Report Date: 13 January 2020
Previous Report Date(s): Not Applicable.
Phase of Development: Phase 3
Primary and Secondary Study Objectives and Endpoints:
Table S1. Study Objectives and Endpoints
Type
Primary
Efficacy

Objective

Endpoint

 To assess the efficacy of
PF-04965842 compared withplacebo in subjects aged
12 years and older withmoderate to severe atopic
dermatitis (AD).

 Response based on the Investigator’s
Global Assessment (IGA) score of clear(0) or almost clear (1) (on a 5 point scale)and a reduction from baseline of 2 points
at Week 12. The baseline will be definedas the IGA score on Day 1 pre-dose.
 Response based on the Eczema Area andSeverity Index ≥75% improvement frombaseline (EASI-75) response at Week 12.
The baseline will be defined as the EASI
score on Day 1 pre-dose.

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Protocol B7451013

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives and Endpoints
Secondary
Efficacy

 To evaluate the effect of
PF-04965842 on additional
efficacy endpoints andpatient-reported outcomesover time in subjects aged
12 years and older withmoderate to severe atopic
dermatitis.

Patient-Reported
Outcomes

Page 2

Key Secondary Efficacy Endpoints:
 Response based on at least 4 points
improvement in the severity of pruritus
numerical rating scale (NRS) frombaseline at Weeks 2, 4, and 12.
 Change from Baseline in Pruritus andSymptoms Assessment for Atopic
Dermatitis (PSAAD) total score at
Week 12.
Secondary Efficacy Endpoints:
 Response based on at least 4 points
improvement in the severity of pruritus
numerical rating scale, (describedinterchangeably as Peak Pruritus
Numerical Rating Scale [PP-NRS]) frombaseline at all scheduled time points otherthan Weeks 2, 4 and 12.
 Time from baseline to achieve at least 4
points improvement in the severity ofpruritus NRS scale.
 Response based on the EASI-75 at allscheduled time points except Week 12.
 Response based on the IGA of clear (0) or
almost clear (1) and 2 point reduction
from baseline at all scheduled time points
except Week 12.
Other Efficacy Endpoints:
 Response based on a 50% and 90%
improvement in the EASI total score(EASI-50 and EASI-90) at all scheduled
time points.
 Change from baseline in the percentage
Body Surface Area (BSA) affected at allscheduled time points.
 Response based on a 50% and 75%
improvement in Scoring Atopic Dermatitis(SCORAD) (SCORAD50, SCORAD75)
from baseline at all scheduled time points.
 Change from baseline at all scheduled
time points in SCORAD subjective
assessments of itch and sleep loss.d
 Change from baseline at Week 12 in
Dermatology Life Quality Index (DLQI)

Final Clinical Study Report
Protocol B7451013

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives and Endpoints

Safety To evaluate the safety andtolerability of PF-04965842
in subjects aged 12 years andolder with moderate to severe

Page 3or Children’s DLQI (CDLQI) and at allother scheduled time points.
 Change from baseline at Week 12 in
Hospital Anxiety and Depression Scale(HADS) and at all other scheduled time
points.
 Change from baseline at Week 12 inPatient-Oriented Eczema Measure(POEM) and at all other scheduled time
points.
 Change from baseline of Patient Global
Assessment (PtGA) at Week 12 and at allother scheduled time points.
 Change from baseline of EuroQol Qualityof Life 5-Dimension 5-Level Scale(EQ-5D-5L) or EuroQol Quality of Life
5-Dimension Youth Scale (EQ-5D-Y) at
Week 12 and at all other scheduled time
points.
 Change from baseline of Functional
Assessment of Chronic Illness Therapy
Fatigue Scale (FACIT-F) or Pediatric
FACIT-F (Peds-FACIT-F) at Week 12 andat all other scheduled time points.
 Change from baseline of Short Form-36v2(SF-36v2), acute at Week 12 and at allother scheduled time points.
 Change from baseline of Work
Productivity and Activity Impairment
Questionnaire: Atopic Dermatitis(WPAI:AD) at Week 12 and at all otherscheduled time points.
 Response based on at least 4 points
improvement in the frequency of pruritus
numerical rating scale (NRS) frombaseline at all scheduled time points.a
 Time from baseline to achieve at least 4
points improvement in the frequency ofpruritus NRS scale.a Incidence of treatment emergent adverse
events.
 Incidence of serious adverse events(SAEs) and adverse events (AEs) leading
to discontinuation.

Final Clinical Study Report
Protocol B7451013

CLINICAL STUDY REPORT SYNOPSISMETHODS
Study Design: This was a randomized, double-blind, placebo-controlled, parallel-group,
Phase 3 study to evaluate the efficacy and safety of PF-04965842 (henceforth referred to as
abrocitinib) monotherapy in subjects aged 12 years and older with moderate-to-severe AD
and a body weight ≥40 kg. The treatment duration was 12 weeks. Subjects were screened
within 28 days prior to the first dose of investigational product to confirm that they met the
subject selection criteria for the study. A total of 391 subjects were enrolled from 106 sites
located globally.
Subjects who continued to meet eligibility criteria at baseline underwent Day 1/ baseline
assessments and were randomized in a 2:2:1 ratio to receive abrocitinib 200 mg once daily(QD), abrocitinib 100 mg QD, or placebo. Randomization was stratified by baseline disease
severity (moderate [IGA = 3] vs. severe [IGA = 4] AD), and age <18 and ≥18 years of age.
Diagnosis and Main Criteria for Inclusion: The study population consisted of subjects
aged ≥12 years who met all the following AD criteria:

Clinical diagnosis of chronic AD for at least 1 year prior to Day 1 and had
confirmed AD (Hanifin and Rajka criteria of AD) at the screening and baseline
visits;Documented recent history (within 6 months before the screening visit) of
inadequate response to treatment with topical medications for at least 4 weeks, orfor whom topical treatments are otherwise medically inadvisable (eg, because ofimportant side effects or safety risks), or who have required systemic therapies forcontrol of their disease;Moderate to severe AD (affected BSA 10%, IGA 3, EASI 16, and pruritus
numeric rating scale [NRS] 4 on the day of the baseline visit).

Study Treatment: Subjects were dispensed 2 bottles at each dispensing visit and were to
take one tablet from each bottle, once daily, preferably in the morning, at approximately thesame time of day for 12 weeks (Table S2).

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Table S2. Investigational Product Description
Investigational Product
Description

Vendor Lot
Number

Pfizer Lot Number

Strength/Potency

Dosage Form

PF-04965842 100 mg
round white film coatedtablet (DC)

100 mgTabletPF-04965842 100 mg
round white film coatedtablet (DC)

100 mgTabletPF-04965842 100 mg
round white film coatedtablet (DC)

100 mgTabletPlacebo for
PF-04965842 roundwhite film coated tablet(9 mm)

0 mg

TabletPlacebo for
PF-04965842 roundwhite film coated tablet(9 mm)

0 mg

TabletEfficacy Evaluations:
The co-primary endpoints were:

Response based on the IGA score of clear (0) or almost clear (1); and a reduction frombaseline of 2 points at Week 12.

Response based on the EASI 75% improvement from baseline (EASI-75) at Week 12.

The key secondary efficacy endpoints analyzed were:

Response based on ≥4 points improvement from baseline in the pruritus NRS (NRS4) for
severity at Weeks 2, 4, and 12;

Change from baseline in PSAAD at Week 12.

The secondary efficacy endpoints analyzed were the following:Response based on NRS4 for severity at all time points other than Weeks 2, 4, and 12.

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CLINICAL STUDY REPORT SYNOPSIS
Time to achieve a ≥4-point improvement from baseline in the numerical rating scale(NRS) for severity of pruritus.

Response based on the EASI-75 at all scheduled time points except Week 12.

Response based on the IGA for clear (0) or almost clear (1); and 2 points reduction frombaseline at all scheduled time points except Week 12.

The other secondary efficacy endpoints analyzed were the following:Response based on the IGA for clear (0) at all scheduled time points.

Response based on a 50%, 90%, and =100% improvement in the EASI total score(EASI-50, EASI-90, and EASI-100) at all scheduled time points.



Percent change from baseline at all scheduled time points in the EASI total score.



Change from baseline in %BSA (from EASI) affected at all scheduled time points.



Proportion of patients with %BSA (from EASI) <5% at all scheduled time points.

Response based on a 50% and 75% improvement in SCORAD (SCORAD50,SCORAD75) from baseline at all scheduled time points.



Percent change from baseline at all scheduled time points in the SCORAD total score.



Change from baseline at all scheduled time points in SCORAD subjective visual analog
scale (VAS) assessments of sleep loss.

The patient-reported outcome (PRO) secondary endpoints analyzed were the following:

Change from baseline in DLQI/CDLQI at all scheduled time points.



Change from baseline in each component (anxiety and depression) of the HADS score at
all scheduled time points.



Change from baseline in POEM at all scheduled time points.



Change from baseline in PtGA at all scheduled time points.



Change from baseline in EQ-5D-5L/EQ-5D-Y at all scheduled time points.



Change from baseline in FACIT-F/Peds-FACIT-F at Week 12.

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Final Clinical Study Report
Protocol B7451013

CLINICAL STUDY REPORT SYNOPSIS
Statistical Methods: Abrocitinib 200 mg QD was declared superior to placebo if the null
hypothesis of no difference between abrocitinib 200 mg QD versus placebo for bothco-primary endpoints was rejected at the 5% significance level. Similarly,
abrocitinib 100 mg QD was declared superior to placebo if the null hypothesis of
no difference between abrocitinib 100 mg QD versus placebo for both co-primary endpoints
was rejected at the significance level specified below.
A sequential Bonferroni-based iterative multiple testing procedure to strongly control thefamilywise Type 1 error at 5% was used for testing each of the two abrocitinib doses(200 mg QD and 100 mg QD) versus placebo on the primary and key secondary endpoints.
The procedure belonged to a class of consonant multiple test procedures, which are a
subclass of the closed test procedures.
For co-primary and secondary endpoints, binary data at each scheduled visit were analyzed.
The test of hypothesis between the abrocitinib treatment groups versus the placebo groupwere conducted by the Cochran-Mantel-Haenszel (CMH) statistic adjusting for the effect ofrandomization strata; p-values from the CMH statistic were used to establish the superiorityof each dose of abrocitinib to placebo in binary responses. The proportion of responders in
the abrocitinib treatment groups versus the placebo group were summarized by the difference
and its 95% confidence interval (CI) obtained by normal approximation. The difference inproportions was calculated within each randomization stratum. The final estimate of thedifference in proportions was a weighted average of these stratum-specific estimates using
CMH weights. Estimates of the difference in proportions along with the two-sided 95% CI
were also provided for the abrocitinib 200 mg QD group versus the abrocitinib 100 mg QD
group. No hypotheses were tested. In this analysis, subjects who permanently discontinued
study for any reason were defined as “non-responders” at all subsequent visits.
For secondary endpoints, the proportion of responders in each treatment group along with thedifferences in proportion of responders among each pair of treatment groups were obtainedusing the methods described above. To account for the responses which were missing
because the data could not be assessed at the scheduled visits of Weeks 2, 4, 8, and 12 inseveral subjects, a hybrid approach was used. First, an imputation model based on a
generalized linear mixed model (GLMM) was fit to the observed data with treatment, visit,
and treatment-by-visit interaction as fixed factors and a subject-specific normally-distributed
random effect. Second, any responses which were missing due to the subject discontinuingpermanently or due to a rescue medication were defined as “non-response”. Third, any other
response which remained missing at any intermittent visits was multiply imputed under the
missing at random (MAR) assumption. The multiple imputation methodology was used withthe missing not at random (MNAR) weights taken as zero (ie, assuming MAR).
The change from baseline in the PSAAD score was analyzed as longitudinal continuous data.
A mixed-effect, repeated measures (MMRM) model was used. The fixed effects oftreatment, visit, treatment-by-visit interaction, and randomization stratification factors were
included. Visit was modeled as a categorical covariate. An unstructured covariance matrix

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was assumed for the model errors. A compound symmetry covariance matrix was used if themodel with unstructured covariance did not converge.
When modeling the change from baseline values, the variable for visit started with the first
postbaseline visit, and the actual baseline value was included as a covariate. At each visit,
estimates of least squares mean (LSM) values and the LSM differences between the
abrocitinib treated groups and the placebo group were derived from the model. The
corresponding p-values, standard errors, and 95% CIs were also derived from the model.
Estimates of the difference in LSMs along with the two-sided 95% CI were also provided forthe abrocitinib 200 mg QD group versus the abrocitinib 100 mg QD group. No hypotheses
were tested. The MMRM yielded valid inferences in the presence of missing datamechanism which was assumed to be MAR.
RESULTS
Subject Disposition and Demography: A total of 554 subjects were screened and391 subjects were randomized. Higher proportions of subjects in the abrocitinib treatmentgroups completed the study compared with the placebo group (Table S3). The proportion ofsubjects who discontinued was higher in the placebo group compared with either abrocitinib
treatment group; this was primarily accounted for by a higher proportion of subjects who
discontinued due to withdrawal by subject, AEs, and lack of efficacy.

Table S3. Disposition Events Summary

Number (%) of Subjects
Discontinued
Adverse Event
Death
Lack of Efficacy
Lost to Follow-Up
Protocol Deviation
Withdrawal By Subject
Other
Completed

Placebo(N=78)n (%)

PF-04965842
100mg QD
(N=158)n (%)

PF-04965842
200mg QD
(N=155)n (%)

26 (33.3)
8 (10.3)
07 (9.0)1 (1.3)
1 (1.3)9 (11.5)
052 (66.7)

21 (13.3)
5 (3.2)1 (0.6)5 (3.2)1 (0.6)
1 (0.6)6 (3.8)2 (1.3)137 (86.7)

14 (9.0)
5 (3.2)04 (2.6)
1 (0.6)
1 (0.6)
1 (0.6)2 (1.3)141 (91.0)

Completed means completed 12 weeks treatment.
SDTM Creation: 12SEP2019 (22:25) Source Data: adds Output
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CLINICAL STUDY REPORT SYNOPSIS
The analyses of the efficacy and PRO endpoints were performed using the Full Analysis Set(FAS) population, which was defined as all 391 randomized subjects who received at least
1 dose of study medication. Additional supportive analyses of the primary and key
secondary efficacy endpoints were performed for the per protocol analysis set (PPAS), which
excluded 25, 30, and 26 subjects in the abrocitinib 200 mg QD, abrocitinib 100 mg QD, andplacebo groups, respectively, resulting in an overall 79.2% of the total FAS population. The
analysis of AEs and laboratory data was performed for the Safety Analysis Set, which
comprised all subjects who received at least 1 dose of study medication and was identical to
the FAS population.
Baseline demographic and disease characteristics were balanced across treatment groups.
The median age of subjects randomized across treatment groups was 31.0 years, withapproximately 10% of subjects who were adolescents aged 12 to <18 years at the time ofscreening. The majority of subjects across treatment groups were white (59.3%); 33.0% of
all subjects were of Asian descent and 5.4% were Black or African American. The mediandisease duration (Q1, Q3) was approximately 19.6 years (9.2, 29.2). Randomized subjects
were representative of the moderate to severe AD population, with all subjects with moderate(67.8%) or severe (32.3%) IGA, median EASI score of 25.2, median PP-NRS of 7.0, andbaseline PRO values representative of a high burden of disease and impact on quality of life
(QoL).

Efficacy Results:
Co-Primary Endpoints
The study met both co-primary endpoints of IGA response at Week 12 and EASI-75 responseat Week 12 demonstrating that both abrocitinib 200 mg QD and 100 mg QD treatmentgroups were superior to the placebo group (Table S4 and Table S5). Additional supportive
sensitivity analysis results based on the PPAS and a tipping point analysis (where all missing
responses were multiply imputed) were consistent with the FAS primary analysis.

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CLINICAL STUDY REPORT SYNOPSIS
Table S4. Proportion of Subjects Achieving Investigator's Global Assessment (IGA)
Response of 'Clear' or 'Almost Clear' and >=2 Points Improvement fromBaseline at Week 12 - CMH (FAS, NRI)Nn (%)
95% CI

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

77
7 (9.1)(2.7, 15.5)

155
44 (28.4)(21.3, 35.5)

155
59 (38.1)(30.4, 45.7)

19.3(9.6, 29.0)
0.000828.7(18.6, 38.8)<.0001

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)
95% CI

9.7(-0.7, 20.0)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (Day 1).
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; N = number of subjects in the analysis set with NRI at the
specified visit; n (%) = number of subjects with response (percentage based on N); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference
for each randomization stratum using thenormal approximation of binomial proportions. The confidence interval for the response rate was based on normal
approximation (or the Clopper-Pearson exact method when there were no or if all were responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by randomization strata (baseline
disease severity and age category).
SDTM Creation: 12SEP2019 (22:27) Source Data: adad Output
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Table S5. Proportion of Subjects Achieving Eczema Area and Severity Index (EASI)
Response >= 75% Improvement from Baseline at Week 12 - CMH (FAS,
NRI)

N
n (%)
95% CI

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

77
8 (10.4)(3.6, 17.2)

155
69 (44.5)(36.7, 52.3)

154
94 (61.0)(53.3, 68.7)

33.9(23.3, 44.4)<.000150.5(40.0, 60.9)<.0001

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)
95% CI

16.5(5.6, 27.4)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (Day 1).
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; N = number of subjects in the analysis set with NRI at the
specified visit; n (%) = number of subjects with response (percentage based on N); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference
for each randomization stratum using thenormal approximation of binomial proportions. The confidence interval for the response rate was based on normal
approximation (or the Clopper-Pearson exact method when there were no or if all were responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by randomization strata (baseline
disease severity and age category).
SDTM Creation: 12SEP2019 (22:46) Source Data: adea Output
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Key Secondary Endpoints
Both key secondary endpoints were met. At Weeks 2, 4, and 12, both abrocitinib treatmentgroups had statistically significantly greater proportions of subjects achieving ≥4 points
improvement from baseline in severity of pruritus NRS (PP-NRS4) responders comparedwith the placebo group (Table S6). Separation from placebo in PP-NRS4 response began as
early as Week 2 in the abrocitinib 200 mg QD and 100 mg QD treatment groups.
At Week 12, the LSM of change from baseline in PSAAD scores showed statisticallysignificant decreases from baseline for both abrocitinib treatment groups compared with theplacebo group (Table S7).

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Table S6. Proportion of Subjects with >=4 Points at Baseline and Achieving >=4
Points Improvement from Baseline in Numeric Rating Scale for Severity ofPruritus - CMH (FAS, NRI after Dropout + MI for Intermittent Missing)

Week 2N
Estimated Response Rate (%)
95% CI

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

76
3.9
(0.0, 8.3)

156
23.1
(16.5, 29.7)

153
35.3
(27.7, 42.9)

19.2(11.0, 27.4)
0.0002

31.2(22.3, 40.2)<.0001

Active - Placebo
Estimate (%)
95% CI
Two-sided P-value
200 mg QD - 100 mg QD
Estimate (%)
95% CI
Week 4N
Estimated Response Rate (%)
95% CI

12.1(2.2, 22.1)
76
4.0(0.0, 8.4)

Active - Placebo
Estimate (%)
95% CI
Two-sided P-value

156
33.4
(25.8, 41.0)

153
52.8
(44.7, 60.8)

29.5(20.5, 38.4)<.0001

48.8(39.5, 58.2)<.0001200 mg QD - 100 mg QD
Estimate (%)
95% CI
Week 8N
Estimated Response Rate (%)
95% CI

19.4(8.4, 30.4)
76
12.0(4.6, 19.4)

Active - Placebo
Estimate (%)
95% CI
Two-sided P-value

156
40.4
(32.6, 48.2)

153
54.4
(46.4, 62.4)

28.5(17.8, 39.3)<.000142.4(31.4, 53.4)<.0001200 mg QD - 100 mg QD
Estimate (%)
95% CI
Week 12N
Estimated Response Rate (%)
95% CI

14.0(2.9, 25.1)
76
11.5(4.1, 19.0)

Active - Placebo
Estimate (%)
95% CI
Two-sided P-value

Page 14156
45.2(37.1, 53.3)

153
55.3
(47.2, 63.5)

33.7(22.8, 44.7)<.000143.9(32.9, 55.0)<.0001

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CLINICAL STUDY REPORT SYNOPSIS
Table S6. Proportion of Subjects with >=4 Points at Baseline and Achieving >=4
Points Improvement from Baseline in Numeric Rating Scale for Severity ofPruritus - CMH (FAS, NRI after Dropout + MI for Intermittent Missing)PlaceboPF-04965842
100mg QD

200 mg QD - 100 mg QD
Estimate (%)
95% CI

PF-04965842
200mg QD

10.2(-1.1, 21.5)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the measurement collected on or prior to Day 1.
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal. Any otherintermittent missing value was handled using multiple imputation.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; GLMM = generalized linear mixed model; MI = multiple
imputation; N = number of subjects in the analysis set with NRI + MI at the
specified visit with baseline >= 4; NRI = non-responder imputation.
At Week 2, no multiple imputations were performed because there were <= 5 subjects with missing responses in alltreatment groups.
SDTM Creation: 12SEP2019 (22:28) Source Data: adnr mif Output
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Table S7. Least Squares Mean of Change from Baseline in Pruritus and Symptoms
Assessment for Atopic Dermatitis (PSAAD) at Week 12 - MMRM (FAS,
OD)

N
LSM
95% CI

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

77

156

155

-0.8
(-1.3, -0.3)-2.4(-2.8, -2.1)-3.0(-3.3, -2.7)-1.7(-2.3, -1.1)<.0001-2.2(-2.8, -1.6)<.0001

Active - Placebo
LSM
95% CI
P-value
200 mg QD - 100 mg QD
LSM
95% CI-0.6(-1.0, -0.1)

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Table S7. Least Squares Mean of Change from Baseline in Pruritus and Symptoms
Assessment for Atopic Dermatitis (PSAAD) at Week 12 - MMRM (FAS,
OD)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the average of all values recorded between Day -6 and Day 1.
Weekly data were average values of daily observations over 7 days.
CI = confidence interval; LSM = least squares mean; N = number of subjects included in the analysis model; OD =observed data.
Mixed Model Repeated Measure (MMRM) contained fixed factors of treatment, visit, treatment by visit interaction,
randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.
SDTM Creation: 12SEP2019 (22:43) Source Data: adpu Output
File: ./nda1 cdisc/B7451013/adpu s103 Date of Generation: 18OCT2019 (10:27)
Table 14.2.4.2.3 is for Pfizer internal use.

Secondary Efficacy Endpoints
The secondary efficacy endpoints showed improved efficacy in both abrocitinib treatmentgroups compared with the placebo group.


At Week 8, both abrocitinib treatment groups had greater proportions of PP-NRS4
responders compared with the placebo group (Table S6).

The Kaplan-Meier analysis to estimate the time to first PP-NRS4 showed shorter mediantimes in both abrocitinib treatment groups compared with the placebo group (Figure S1).

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Protocol B7451013

CLINICAL STUDY REPORT SYNOPSISSCORAD Sleep Loss: Both abrocitinib treatment groups demonstrated decreases in
SCORAD VAS of sleep loss absolute and percent change from baseline compared with theplacebo group beginning at Week 2 that were maintained up to Week 12, except for Weeks 2
and 12 in the abrocitinib 100 mg QD group.
Patient-Reported Outcomes
DLQI/CDLQI: For DLQI (adult subjects), both abrocitinib treatment groups showeddecreased DLQI scores compared with the placebo group that occurred as early as Week 2
and were maintained up to Week 12. For CDLQI (adolescent subjects), the sample sizes
were low (15 subjects in the abrocitinib 200 mg QD group, 16 subjects in the abrocitinib
100 mg QD group, and 8 subjects in the placebo group) and showed decreased CDLQI scorescompared with the placebo group beginning as early as Week 2 in the abrocitinib 200 mg QD
group and at no time point in the abrocitinib 100 mg QD group.
HADS: The LSM of change from baseline in HADS anxiety sub-scores was improved(lower) for both abrocitinib treatment groups compared with the placebo group beginning at
Week 2 and maintained at all subsequent time points, except at Week 8 in the abrocitinib
100 mg QD group. The LSM of change from baseline in HADS depression sub-scores was
improved (lower) for both abrocitinib treatment groups compared with the placebo groupbeginning at Week 2 and maintained at all subsequent time points.
POEM: The LSM of change from baseline in POEM scores was improved (lower) for both
abrocitinib treatment groups compared with the placebo group beginning at Week 2 that weremaintained up to Week 12.
PtGA: The LSM of change from baseline in PtGA scores was improved (lower) for both
abrocitinib treatment groups compared with the placebo group beginning at Week 2 that weremaintained up to Week 12.
EQ-5D-5L/EQ-5D-Y: For the EQ-5D-5L index value, the LSM of change from baseline
was improved (higher) for both abrocitinib treatment groups compared with the placebogroup beginning at Week 2 that were maintained at all scheduled time points. For the
EQ-5D-5L EQ VAS score, the LSM of change from baseline was improved (higher) for both
abrocitinib treatment groups compared with the placebo group beginning at Week 2 that weremaintained at all scheduled time points, except for Week 8 in the abrocitinib 100 mg QD
group.
FACIT-F/ Peds-FACIT-F: The LSM of change from baseline for FACIT-F in adultsubjects was improved (higher scores) for both abrocitinib treatment groups compared withthe placebo group at Week 12. The LSM of change from baseline for Peds-FACIT-F inadolescent subjects was not different for both abrocitinib treatment groups compared with theplacebo group at Week 12; however, the number of adolescent subjects was low in alltreatment groups.

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Protocol B7451013

CLINICAL STUDY REPORT SYNOPSIS

The incidence of subjects who permanently discontinued from the study due to TEAEs
was lower in the abrocitinib treatment groups compared with the placebo group.



The incidence of subjects with temporary discontinuations of study drug due to a TEAE
was similar between the abrocitinib treatment groups and the placebo group.

Table S8. Treatment-Emergent Adverse Events (All Causalities)

Number (%) of Subjects
Subjects evaluable for adverse events
Number of adverse events
Subjects with adverse events
Subjects with serious adverse events
Subjects with severe adverse events
Subjects discontinued from study due to adverse events [1]Subjects discontinued study drug due to AE and continued Study [2]Subjects with temporary discontinuation due to adverse events

Placebon (%)

PF-04965842
100mg QDn (%)

PF-04965842
200mg QD
n (%)

78

158

155

70
42 (53.8)
1 (1.3)5 (6.4)10 (12.8)0
2 (2.6)204
99 (62.7)
5 (3.2)7 (4.4)6 (3.8)2 (1.3)8 (5.1)245
102 (65.8)
2 (1.3)6 (3.9)5 (3.2)05 (3.2)

Included data up to 28 days after last dose of study.
Except for the number of adverse events subjects were counted only once per treatment in each row.
Serious Adverse Events - according to the investigator's assessment[1] Subjects who had an AE record that indicated that the AE caused the subject to be discontinued from the study[2] Subjects who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE
did not cause the subject to be discontinued from study
MedDRA v22.0 coding dictionary applied.
SDTM Creation: 12SEP2019 (22:27) Source Data: adae Output
File: ./nda1 cdisc/B7451013/adae s010 Date of Generation: 18OCT2019 (00:24)
Table 14.3.1.2.1 is for Pfizer internal use.

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CLINICAL STUDY REPORT SYNOPSIS

Conclusions:
EFFICACY
Co-Primary Endpoints:
Both abrocitinib treatment groups (200 mg QD and 100 mg QD) met the co-primary
endpoints of IGA response of clear (0) or almost clear (1) and 2-points improvementfrom baseline at Week 12 and EASI response 75% improvement from baseline at
Week 12 compared with the placebo group.
o Statistically significantly higher placebo-corrected proportions of subjects achieved
IGA responses and EASI-75 responses for both abrocitinib treatment groups
compared with the placebo group.
o IGA responses and EASI-75 responses (placebo-corrected) in the abrocitinib 200 mg
QD group were approximately 50% higher than the abrocitinib 100 mg QD group.
o Sensitivity analyses of IGA and EASI-75 responses were consistent with the primary
analyses.
o The treatment effects for both IGA response and EASI-75 response were similar
across subgroups.

Key Secondary Endpoints:
Both abrocitinib treatment groups (200 mg QD and 100 mg QD) met the key secondary
endpoints of PP-NRS4 response at Weeks 2, 4, and 12, and PSAAD change frombaseline at Week 12.
o Both abrocitinib treatment groups (200 mg QD and 100 mg QD) showed statisticallysignificantly greater proportions of PP-NRS4 responders compared with the placebogroup at Weeks 2, 4, and 12. Separation from placebo in PP-NRS4 response began as
early as Week 2 in the abrocitinib 200 mg QD and 100 mg QD treatment groups thatwere maintained at all subsequent scheduled time points.
o Both abrocitinib treatment groups (200 mg QD and 100 mg QD) showed statisticallysignificant decreases from baseline in PSAAD scores compared with the placebogroup at Week 12. As early as Week 1, the LSM of change from baseline for both
abrocitinib treatment groups were decreased compared with the placebo group, andthe treatment effect of both abrocitinib groups plateaued after Week 5.

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CLINICAL STUDY REPORT SYNOPSIS
Other Secondary Endpoints:
Additional secondary efficacy endpoints (IGA, EASI, PP-NRS, BSA, and SCORAD)
demonstrated improved efficacy in both abrocitinib treatment groups compared with theplacebo group.
IGA

Both abrocitinib treatment groups showed higher IGA responses compared withplacebo at Week 2, suggesting early onset of the treatment effect, and responses weremaintained at Weeks 4 and 8.

EASIBoth abrocitinib treatment groups demonstrated higher EASI-50 responses and
EASI-90 responses compared with the placebo group.

The higher EASI-50 responses and EASI-90 responses compared with the placebogroup began as early as Week 2 and were maintained through Week 12.

Both abrocitinib treatment groups had higher EASI-75 responses compared withplacebo at Week 2, suggesting early onset of the treatment effect, and responses weremaintained at Weeks 4 and 8.

PP-NRSThe LSM of change from baseline in PP-NRS was lower in both abrocitinib groups
compared with the placebo group as early as Day 2 (24 hours after the first dose),demonstrating a rapid onset of the treatment effect, which was maintained throughWeek 12.



The median time to achieve first PP-NRS4 was faster in both abrocitinib treatmentgroups compared with the placebo group. In the abrocitinib 200 mg QD and 100 mg
QD groups, 50% improved by 29 days and 58 days, respectively, compared with theplacebo group.

BSA

Both abrocitinib treatment groups demonstrated decreases in absolute and percent
change from baseline in %BSA compared with the placebo group as early as Week 2that were maintained up to Week 12.

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Final Clinical Study Report
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CLINICAL STUDY REPORT SYNOPSISSCORADBoth abrocitinib treatment groups demonstrated higher SCORAD50 responses
compared with the placebo group as early as Week 2 that were maintained up to
Week 12.

Both abrocitinib treatment groups demonstrated higher SCORAD75 responses
compared with the placebo group beginning at Week 2 for the abrocitinib 200 mg QD
group and at Week 4 for the abrocitinib 100 mg QD group.

Both abrocitinib treatment groups demonstrated decreases in SCORAD total scoreabsolute and percent change from baseline compared with the placebo groupbeginning at Week 2 that were maintained up to Week 12.

Both abrocitinib treatment groups demonstrated decreases in SCORAD VAS of sleep
loss absolute change from baseline and percent change from baseline compared withthe placebo group beginning at Week 2 that were maintained up to Week 12, except
for percent change from baseline at Weeks 2 and 12 in the abrocitinib 100 mg QD
group.

Across all secondary efficacy endpoints evaluated, the treatment effect of the abrocitinib
200 mg QD group was consistently higher than the abrocitinib 100 mg QD group.

Patient-Reported Outcomes (PROs):

Favorable and improved differences across all PRO measures were observed for both
abrocitinib treatment groups compared with the placebo group at Week 12. For all adultmeasures assessed (DLQI, HADS, POEM, PtGA, EQ-5D-5L, FACIT-F, SF-36v2, and
WPAI:AD), treatment differences emerged as early as Week 2 and were maintained atsubsequent time points up to Week 12.


There was an improvement in dermatology-related QoL in the DLQI assessments inboth abrocitinib treatment groups compared with the placebo group.

An improvement in symptoms associated with depression and anxiety in the HADS
sub-scores in subjects in both abrocitinib treatment groups compared with the placebogroup was seen at all time points, except at Week 8 in the abrocitinib 100 mg QD
group for the HADS anxiety sub-score.

An improvement in the frequency of symptoms associated with atopic dermatitis in
the POEM assessment was seen in both abrocitinib treatment groups compared withthe placebo group.

An improvement in patient impression of severity of disease within the PtGA wasseen in both abrocitinib treatment groups compared with the placebo group.

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CLINICAL STUDY REPORT SYNOPSIS
SAFETY

Abrocitinib was well tolerated. Safety concerns were manageable.



A higher proportion of subjects with all-causality TEAEs occurred in the abrocitinib
groups compared with the placebo group.
o All-causality TEAEs that appeared more commonly in the abrocitinib groups relative
to the placebo group included nausea, headache, nasopharyngitis, upper respiratory
tract infection, and acne.
o Most all-causality TEAEs (>95%) were mild or moderate in severity.
o The incidence of severe TEAEs was similar between the abrocitinib treatment groups
and the placebo group, with most related to atopic dermatitis.
o TEAEs relating to atopic dermatitis exacerbation were more frequent in the placebogroup compared with the abrocitinib treatment groups.



The incidence of SAEs was low and similar in all treatment groups (1.3%-3.2%).

The incidence of subjects who permanently discontinued from the study due to TEAEs
was lower in the abrocitinib treatment groups compared with the placebo group.



There was one fatal event of sudden death in the abrocitinib 100 mg QD group, which
was assessed as not related to the study drug by the investigator and was confirmed tomeet criteria for a cardiovascular event.



The incidence of subjects with herpes zoster was low with 2/155 in the abrocitinib
200 mg QD group, 0/158 in the abrocitinib 100 mg QD group, and no subject in theplacebo group.



Platelet counts decreased in a dose-dependent manner in both abrocitinib groups with anadir at Week 4 and returned toward baseline through Week 12 despite continued
abrocitinib administration in the majority of subjects. Two (2) subjects in the abrocitinib
200 mg QD group met pre-specified monitoring criteria, but no subject met pre-specified
discontinuation criteria. Median lymphocyte counts, neutrophil counts, and hemoglobinvalues showed no clinically meaningful median changes.



There were increases in total cholesterol, LDL-cholesterol, and HDL-cholesterol, forwhich dose-dependent changes were observed for total cholesterol and HDL-cholesterol.
There were no changes over time in LDL/HDL ratio and triglycerides.

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CLINICAL STUDY REPORT SYNOPSIS

Dose-dependent increases in creatine kinase were observed in the abrocitinib groups
compared with the placebo group but were not clinically meaningful. There were no
TEAEs of rhabdomyolysis.



There were no malignancies or venous thromboembolic events across treatment groups.



There were no QTcF interval changes or vital signs changes of critical concern.

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