Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Sponsor: Pfizer Inc
Investigational Product: tofacitinib
Clinical Study Report Synopsis: Protocol A3921288
Protocol Title: A Phase 3b/4, Multi-Center, Double-Blind, Randomized, Parallel Group
Study of Tofacitinib (CP-690,550) in Subjects With Ulcerative Colitis in Stable Remission
Investigators: Refer to Appendix 16.1.4.1 for a list of investigators involved in this study.
Study Center(s): A total of 69 sites randomized subjects from the following countries:
Belgium (1), Canada (2), Czech Republic (1), France (2), Germany (1), Hungary (3), Italy(1), Japan (14), Republic of Korea (3), Netherlands (1), New Zealand (3), Poland (2),Russian Federation (2), Serbia (5), Slovakia (3), South Africa (4), Spain (1), Ukraine (4),
United Kingdom (1), and the United States (15). Refer to Appendix 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: 16 November 2017
Study Completion Date: Data Cut Off Date: 20 February 2020
Report Date: 22 July 2020
Previous Report Date(s): Not applicable
Phase of Development: Phase 3b/4
Study Objectives and Endpoints:
Table S1.

Study Objectives and Endpoints

Type
Primary Efficacy
Efficacy

Objective
To evaluate the efficacy of
tofacitinib in subjects in stableremission on 10 mg twice
daily (BID) who decrease thedose to and remain on 5 mg
BID (“5 mg BID dose group”)
compared to subjects
remaining on 10 mg BID.

Secondary Efficacy

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Endpoint

Remission based on
modified Mayo score at
Month 6.

Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Table S1.

Study Objectives and Endpoints
Type

Efficacy

SafetySafetyObjective
To evaluate the efficacy of
tofacitinib in subjects in stableremission on 10 mg BID who
decrease the dose to andremain on 5 mg BID (“5 mg
BID dose group”) compared tosubjects remaining on 10 mg
BID.

To evaluate the safety of
tofacitinib in subjects in stableremission on 10 mg BID who
decrease the dose to andremain on 5 mg BID (“5 mg
BID dose group”) compared to

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Page 2Endpoint
Time to loss of remission
based on modified Mayoscore.



Remission at all
applicable scheduled visits
based on the following:
modified Mayo score(excluding Month 6),
modified partial Mayoscore (PMS), total Mayoscore, and PMS.



Change from baseline (ofStudy A3921288) at all
applicable scheduled visits
in the following: modified
Mayo score, modified
PMS, total Mayo score,and PMS.



Mucosal healing at all
applicable scheduledvisits.



Clinical response based on
Mayo score at all
applicable scheduledvisits.



Change from baseline at
all applicable scheduledvisits in fecal calprotectin(FCP) and high sensitivity
C-reactive protein(hsCRP) levels.



Incidence and severity ofadverse events (AEs).



Incidence of serious
infections.

Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Table S1.

Study Objectives and Endpoints
Type

Objective
subjects remaining on 10 mg
BID.

Endpoint
Incidence and severity ofclinical laboratory
abnormalities and change
from baseline in clinicallaboratory values.



Incidence of vital signabnormalities and change
from baseline in vital
signs.



Incidence of clinicallysignificant changes inphysical examinations
from baseline.



Adjudicated safety events(eg, opportunistic
infections, malignancy,
gastrointestinal
perforation, andcardiovascular events).

METHODS
Study Design: This study enrolled subjects from the ongoing open-label long-term
extension (LTE) Study A3921139 who were in stable remission (see Diagnosis and Main
Criteria for Inclusion below) on tofacitinib 10 mg BID for at least 6 months and not receiving
any corticosteroids to treat their ulcerative colitis (UC) for at least 4 weeks prior toenrollment. Subjects must have received tofacitinib 10 mg BID for a minimum of
2 consecutive years in the ongoing open-label LTE Study A3921139 prior to enrollment.
Subjects enrolling under Amendment 2 must not have had any risk factors for pulmonary
embolism.
Approximately 130 subjects were estimated to be enrolled into this study (based on
availability of eligible subjects from the ongoing open-label LTE Study A3921139 and basedon the conservative assumptions of the attrition rate of 50% - 60% in the ongoing open-label
LTE Study A3921139). Eligible subjects were randomized in a 1:1 allocation ratio to receive
either tofacitinib 5 mg BID or 10 mg BID at baseline of this study. Subjects were stratified
at baseline based on the endoscopic subscore (ESS) (0 versus 1) of their most recent
endoscopy (Figure S1).

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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
This study will have a total of 42 months of treatment duration. The primary analysis was
conducted after the last subject enrolled reached their Month 6 study visit. The initial
treatment assignment at baseline will remain double-blinded to the site and the subject.
Any time after Month 1, subjects who experienced flare could have had their dose escalated.
Flare was defined by meeting 1 of the following 4 criteria:
1. An increase in rectal bleeding subscore by at least 1 point and an increase in ESS by
at least 1 point; OR
2. An increase in rectal bleeding subscore by at least 2 points and an ESS >0; OR
3. An increase in stool frequency subscore by at least 2 points and an increase in the
ESS by at least 1 point; OR
4. An increase in ESS by at least 2 points.
Subjects with confirmed flare were eligible for a dose escalation.
Figure S1. Study Design

Diagnosis and Main Criteria for Inclusion: Key inclusion criteria were as follows:
1. Subjects enrolled in Study A3921139 who had received tofacitinib 10 mg BID for aminimum of 2 consecutive years in Study A3921139 prior to and including baselineof Study A3921288.
2. Subjects who were in stable remission on tofacitinib 10 mg BID for the 6 month
period in Study A3921139 up to and including baseline of Study A3921288, defined
as meeting all of the following criteria:

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Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
a. A partial Mayo score 2, with no individual subscore >1 and a rectal bleeding
subscore of 0 at each study visit where data were available during the 6 month
period in Study A3921139 prior to and including baseline of Study A3921288;
b. AND at least 1 assessment of remission based on Mayo score;

If an endoscopy was not completed 6 months prior to baseline of
Study A3921288, then an endoscopy performed in Study A3921139 with an
ESS of 0 or 1, was required prior to randomization into Study A3921288.

All available assessments based on Mayo score during this period must haveshown remission.

c. AND subjects must not have been receiving any corticosteroid therapy for their
UC for at least 4-weeks prior to baseline.
Study Treatment: Eligible subjects were randomized in a 1:1 allocation ratio to receive
either tofacitinib 5 mg BID or 10 mg BID at baseline of Study A3921288. Subjects werestratified at baseline based on the ESS (0 versus 1) of their most recent endoscopy.
Subjects who met the protocol definition for flare could have had a dose increase to
10 mg BID or remained on 10 mg BID, depending on their initial treatment assignment,
provided that the subject did not have any of the risk factors for pulmonary embolism(beginning with Protocol Amendment 2).
Details of the investigational product used in the is study are shown in Table S2.
Table S2. Investigational Product Description
Investigational
Product Description
Placebo for Tofacitinib
Citrate 5 mg Film
Coated Tablet
Placebo for Tofacitinib
Citrate 5 mg Film
Coated Tablet
Tofacitinib Citrate
5 mg Film Coated
TabletTofacitinib Citrate
5 mg Film Coated
TabletVendor Lot
NumberR73682

Pfizer Lot
Number16-005146

Strength/Potency

Dosage Form

0 mg

Tablet

R7368316-005147

0 mg

Tablet

S2691817-000460

5 mg

TabletX20921

18-002302

5 mg

TabletEfficacy Evaluations:

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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Mayo Score
The Mayo score is an instrument designed to measure disease activity of UC. Mayo score
ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higherscores indicating more severe disease.
stool frequency (0-3).



rectal bleeding (0-3).

findings of flexible sigmoidoscopy (0-3).



physician global assessment (PGA) (0-3).

Endpoints based on total Mayo score are defined below:Remission: total Mayo score of 2 points or lower, with no individual subscoreexceeding 1 point and a rectal bleeding subscore of 0.



Clinical response: decrease from baseline in total Mayo score of the Induction study,of at least 3 points and at least 30%, with an accompanying decrease in the subscore
for rectal bleeding of at least 1 point, or absolute subscore for rectal bleeding of
0 or 1.

Mucosal healing: an ESS of 0 or 1.

Modified Mayo score consists of stool frequency subscore, rectal bleeding subscore and ESS(ie, total Mayo score without PGA).
Endpoints based on modified Mayo score are defined below:Remission: an ESS of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding
subscore of 0.

Partial Mayo Score
A PMS is an instrument designed to measure disease activity of UC without endoscopy.
PMS ranges from 0 to 9 points. It consists of 3 subscores, each graded from 0 to 3 withhigher scores indicating more severe disease.
stool frequency (0-3);



rectal bleeding (0-3);

physician global assessment (PGA) (0-3).
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Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Endpoints based on PMS are defined below:Remission: PMS of 2 points or lower, with no individual subscore exceeding 1 point
and a rectal bleeding subscore of 0.

Modified PMS consists of stool frequency and rectal bleeding subscores (ie, PMS without
PGA).
Endpoints based on modified PMS are defined below:Remission: stool frequency subscore of 0 or 1, and a rectal bleeding subscore of 0.

Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, and/or Other Evaluations:
No pharmacokinetic, pharmacodynamic or pharmacogenomic evaluations were performed inthis study.
Safety Evaluations: Safety was assessed by vital signs (blood pressure, pulse rate, andtemperature), physical examinations, clinical laboratory tests (including FCP and hsCRP) andthe spontaneous reporting of AEs, in all subjects who received at least 1 dose ofinvestigational product.
Statistical Methods:
Analysis of the Primary Endpoint
The primary efficacy endpoint was remission based on modified Mayo score at Month 6. For
dose comparison between tofacitinib 10 mg BID and 5 mg BID, the stratified estimation of
the treatment difference between tofacitinib 10 mg BID and 5 mg BID in the proportion ofsubjects was presented along with its 95% confidence interval (CI) with the ESS at baseline(0 versus 1) as the stratification factor. The Cochran Mantel Haenszel (CMH) weight
method was used for the stratified estimation of the treatment difference. The stratified CI
was constructed using the NewCombe method by Yan and Su.
In addition, p-values based on CMH Chi-square test stratified by ESS at baseline (0 versus 1)
were presented.
Analysis of the Secondary Endpoints
Binary secondary efficacy endpoints were analyzed using the same approach as described forthe primary efficacy endpoint.
For continuous efficacy endpoints based on total Mayo score evaluated for primary objectiveat Month 6, the change from baseline was analyzed using an analysis of covariance(ANCOVA) model with dose group, the ESS at baseline (0 versus 1) as factors and baseline
score as a covariate. Otherwise, for continuous efficacy endpoints, the change from baseline
was analyzed using linear mixed effects model with baseline value, dose group, the ESS at
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Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
baseline (0 versus 1), visit, and dose group by visit interaction all as fixed effects, and subject
as a random effect. The adjusted estimations and associated 95% CI for the overall
difference between the 2 dose groups was computed for each visit.
Time to loss of remission (flare) based on modified Mayo score was estimated using a
log-rank test stratified by ESS at baseline (0 versus 1). In addition, cumulative event rates
and associated CIs were estimated from the Kaplan-Meier curves for each dose group. The
dose comparison for the proportions of the event were made using Wald test statistics.
FCP and hsCRP, and their change from baseline were summarized descriptively for each
visit by dose group.
The FCP and hsCRP data were also log-transformed (natural logarithm) for the analyses.
The change from baseline was analyzed using the same approach as the continuous efficacy
endpoints.
The safety data were summarized in accordance with Pfizer Data Standards.
RESULTS
Subject Disposition and Demography: Subject disposition is presented in Figure S2.


A total of 140 subjects were randomized into the study, with 70 subjects randomized toeach treatment group.

Discontinuation rates were similar between treatment groups.



The most common reasons for discontinuation were AEs (5 subjects) and withdrawal bysubject (5 subjects) in the tofacitinib 5 mg BID group, and withdrawal by subject(10 subjects) in the tofacitinib 10 mg BID group.

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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Figure S2. Subject Disposition

Subjects who discontinued due to an AE of ‘worsening UC’ were summarized under lack of efficacy.

Efficacy Results:
Primary Endpoint Result
Remission Based on Modified Mayo Score at Month 6
The proportion of subjects in remission based on modified Mayo score at Month 6 washigher for the tofacitinib 10 mg BID (90.0%) group compared with the tofacitinib 5 mg BID
group (77.1%) with a difference of 12.9% (95% CI: 0.5, 25.0).
Secondary Endpoint Results
Consistent results were observed in the secondary endpoints to support the results of the
primary endpoint.
Remission (Based on Total Mayo Score)

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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
The proportion of subjects in remission based on total Mayo score at Month 6 was higher forthe tofacitinib 10 mg BID (87.1%) group compared with the tofacitinib 5 mg BID group(75.7%) with a difference of 11.4% (95% CI: -1.5, 24.1).
Mucosal Healing
The proportion of subjects with mucosal healing at Month 6 was higher for the tofacitinib
10 mg BID (91.4%) group compared with the tofacitinib 5 mg BID group (80.0%) with adifference of 11.4% (95% CI: -0.3, 23.1).
Clinical Response
The proportion of subjects with a clinical response at Month 6 was higher for the tofacitinib
10 mg BID (95.7%) group compared with the tofacitinib 5 mg BID group (84.3%) with adifference of 11.4% (95% CI: 1.3, 22.0).
Remission Based on Modified Partial Mayo Score and Partial Mayo ScoreFor all subjects, the proportions of subjects in remission based on modified partial Mayoscore (PMS) and PMS were higher for the tofacitinib 10 mg BID group compared withthe tofacitinib 5 mg BID group at each time point assessed (Months 1, 3 and 6).
At Month 1, 91.4% in the tofacitinib 10 mg BID group and 88.6% in the tofacitinib
5 mg BID group with a difference of 2.9% (95% CI:-7.5, 13.4) for both modified
PMS and PMS.

At Month 3, 92.9% in the tofacitinib 10 mg BID group and 81.4% in the tofacitinib
5 mg BID group with a difference of 11.4% (95% CI: 0.1, 22.8) for both modified
PMS and PMS.

At Month 6, 95.7% in the tofacitinib 10 mg BID group and 81.4% in the tofacitinib
5 mg BID group with a difference of 14.3% (95% CI: 2.9, 25.2) for modified PMS
and 94.3% in the tofacitinib 10 mg BID group and 80.0% in the tofacitinib 5 mg BID
group with a difference of 14.3% (95% CI: 2.4, 25.6) for PMS.

Change From Baseline of Modified Mayo and Total Mayo Score at Month 6
The least square (LS) mean [standard error (SE)] for the change from baseline ofmodified Mayo score at Month 6 was lower for the tofacitinib 10 mg BID group (0.3[0.2]) compared with the tofacitinib 5 mg BID group (0.6 [0.2]) based on ANCOVA.

The LS mean [SE] for the change from baseline of total Mayo score at Month 6 waslower for the tofacitinib 10 mg BID group (0.4 [0.3]) compared with the tofacitinib 5 mg
BID group (0.9 [0.2]) based on ANCOVA.

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CLINICAL STUDY REPORT SYNOPSIS
Change From Baseline of Modified Partial Mayo Score and Partial Mayo Score
The LS mean changes (SE) from baseline for the modified PMS and PMS remained low
over time (Months 1, 3 and 6) and were either the same or similar for both dose groups.


At Month 1, 0.2 (0.1) in the tofacitinib 10 mg BID group and 0.1 (0.1) in thetofacitinib 5 mg BID group for modified PMS and 0.2 (0.1) for both dose groups forPMS.

At Month 3, 0.1 (0.1) in the tofacitinib 10 mg BID group and 0.2 (0.1) in thetofacitinib 5 mg BID group for modified PMS and 0.2 (0.1) in the tofacitinib 10 mg
BID and 0.3 (0.1) in the tofacitinib 5 mg BID group for PMS.

At Month 6, 0.2 (0.1) in the tofacitinib 10 mg BID group and 0.1 (0.1) in thetofacitinib 5 mg BID group for modified PMS and 0.3 (0.1) for both dose groups for
PMS.

Subgroup Analyses
Subgroup analyses were conducted for the primary efficacy and secondary efficacy endpoints
for ESS at baseline (0, 1), prior tumor necrosis factor inhibitor (TNFi) failure (Y/N) and prior
TNFi exposure (Y/N).
Remission Based on Modified Mayo Score at Month 6
The proportion of subjects in remission based on modified Mayo score at Month 6 washigher in both dose groups for subjects with a baseline ESS=0 compared with subjects
with a baseline ESS=1.



For both subgroups based on baseline ESS=0 and ESS=1, the proportion of subjects inremission based on modified Mayo score at Month 6 was higher in the tofacitinib 10 mg
BID group compared with the tofacitinib 5 mg BID group.

The observed difference between tofacitinib 10 mg BID and 5 mg BID in proportions ofsubjects in remission at Month 6 was higher in the subgroup with baseline ESS=1 than
the subgroup with baseline ESS=0.


ESS=0: 92.2% for the tofacitinib 10 mg BID group compared with 82.4% for thetofacitinib 5 mg BID group with a difference of 9.8% (95% CI: -3.0, 22.6).



ESS=1: 84.2% for the tofacitinib 10 mg BID group and 63.2% for the tofacitinib
5 mg BID group with a difference of 21.1% (95% CI: -6.1, 48.2).

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Final Clinical Study Report
Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSISThe proportions of subjects in remission based on modified Mayo score at Month 6 in thesubgroup with prior TNFi failure and the subgroup without prior TNFi failure werehigher in the tofacitinib 10 mg BID group compared with the tofacitinib 5 mg BID group.

The observed difference between tofacitinib 10 mg BID and 5 mg BID in proportions ofsubjects in remission at Month 6 was higher in the subgroup with prior TNFi failure than
the subgroup without prior TNFi failure.

Prior TNFi failure=Yes: 91.4% for the tofacitinib 10 mg BID group compared with
74.1% for the tofacitinib 5 mg BID group with a difference of 17.4% (95% CI: -1.6,
36.3).



Prior TNFi failure=No: 88.6% for the tofacitinib 10 mg BID group and 79.1% for thetofacitinib 5 mg BID group with a difference of 9.5% (95% CI: -6.6, 25.6).

Trends were similar for the subgroup of prior TNFi exposure.

Subgroup results were similar for the secondary endpoints of remission based on total Mayoscore at Month 6, remission based on modified partial Mayo score and partial Mayo score,mucosal healing at Month 6, and clinical response.
Time to Loss of Remission (Flare) Based on Modified Mayo Score
Any time after Month 1, subjects who experienced flare may have had their dose escalated.
In the tofacitinib 10 mg BID group, 4 subjects had a dose escalation action taken
although the dose was not actually changed; 3 subjects prior to or at Month 6 (study
day ≤190).

In the tofacitinib 5 mg BID group, 12 subjects had a dose escalation to 10 mg BID;
9 subjects prior to or at Month 6 (study day ≤190).

The estimated rates (%) of having loss of remission were numerically lower in the tofacitinib
10 mg BID group compared with the tofacitinib 5 mg BID group at Months 1, 3 and 6(Figure S3). Prior to or at Month 6, there were 4 subjects in the tofacitinib 10 mg BID groupand 10 subjects in the tofacitinib 5 mg BID group that experienced loss of remission.
At Month 1: 1.43% in the tofacitinib 10 mg BID group compared with 2.90% in thetofacitinib 5 mg BID group with a difference of -1.47 (95% CI: -6.31, 3.37).

At Month 3: 1.43% in the tofacitinib 10 mg BID group compared with 5.84% in thetofacitinib 5 mg BID group with a difference of -4.41 (95% CI: -10.62, 1.80).

At Month 6: 5.74% in the tofacitinib 10 mg BID group compared with 14.77% in thetofacitinib 5 mg BID group with a difference of -9.03 (95% CI: -19.10, 1.03).
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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS
Figure S3. Kaplan‑Meier Plot of Time to Loss of Remission (Flare) based on Modified
Mayo Score by Dose Group (FAS)

Change from Baseline in Fecal Calprotectin and hsCRP Levels
FCP Levels
Median baseline FCP values were similar between the treatment groups, 48.0 µg/g and 54.0µg/g in the tofacitinib 10 mg BID group and tofacitinib 5 mg BID group, respectively.


There were no meaningful differences in FCP values between the dose groups over time.

hsCRP Levels
Baseline median hsCRP values were similar between the treatment groups, 0.7 mg/L and 0.5
mg/L in the tofacitinib 10 mg BID group and tofacitinib 5 mg BID group, respectively.


At Months 1 and 3, the LS mean in the tofacitinib 10 mg BID group showed a decrease
from baseline (-0.3 and -0.1, respectively) in hsCRP compared with the tofacitinib 5 mg
BID group which showed an LS mean increase (0.2 and 0.3, respectively) from baseline
using linear mixed-effects model).

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CLINICAL STUDY REPORT SYNOPSISAt Month 6, the tofacitinib 10 mg BID group showed a lower LS mean increase frombaseline in hsCRP (0.1) compared with the tofacitinib 5 mg BID group (0.3) using linear
mixed-effects model.

Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Immunogenicity and/or
Other Results: No pharmacokinetic, pharmacodynamic or pharmacogenomic evaluations
were performed in this study.
Safety Results:
Data collected after dose escalation from tofacitinib 5 mg BID to 10 mg BID was notincluded in the safety analyses.
The proportion of subjects who experienced all-causality treatment-emergent adverse
events (TEAEs) was similar between the treatment groups (Table S3).


The majority of reported all-causality TEAEs were mild to moderate in both
treatment groups; with the number of subjects with severe TEAEs lower in thetofacitinib 10 mg BID group (2 [2.9%] subjects) compared with the tofacitinib 5 mg
BID group (6 [8.6%] subjects).



There were 4 (5.7%) subjects with SAEs in each treatment group.

Two (2.9%) subjects discontinued the study due to AEs in the tofacitinib 10 mg BID
group compared with 7 (10.0%) subjects (1 [1.4%] subject discontinued study drug but
continued in the study) in the tofacitinib 5 mg BID group.

Two (2.9%) subjects in the tofacitinib 10 mg BID group and 3 (4.3%) subjects in thetofacitinib 5 mg BID group had temporary discontinuations.



No deaths were reported in this study.

No new or unexpected safety findings were observed.


Two cardiovascular events were confirmed by adjudication (1 pulmonary embolism
in the tofacitinib 10 mg BID group; 1 cerebrovascular accident in the tofacitinib 5 mg
BID group).



Four herpes zoster events were reported (1 in the tofacitinib 5 mg BID group; 3 in thetofacitinib 10 mg BID group); 1 herpes zoster event was reported in the tofacitinib
10 mg BID group that met criteria for an opportunistic infection (OI). No events
classified as serious herpes zoster.

No non-herpes zoster OIs were reported.

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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS

One malignancy excluding nonmelanoma skin cancer (NMSC) was confirmed by
adjudication (vulvar cancer in the tofacitinib 5 mg BID group).



One NMSC event was confirmed by adjudication (basal cell carcinoma in thetofacitinib 5 mg BID group).

One hepatic event was adjudicated and assessed as unlikely to be drug induced liver
injury; no potential or confirmed Hy’s Law cases.

No gastrointestinal perforations were reported.

Table S3. Tofacitinib Protocol A3921288 Treatment-Emergent Adverse Events by
Dose Group (All Causalities) - Safety Analysis Set

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 (a)Subjects discontinued study drug due to AE and continue Study(b)
Subjects with dose reduced or temporary discontinuation due toadverse events

Tofacitinib 5 mg
BID
n (%)

Tofacitinib 10 mg
BID
n (%)

Total
n (%)

70

70

140

130
46 (65.7)
4 (5.7)6 (8.6)7 (10.0)
1 (1.4)143
49 (70.0)
4 (5.7)2 (2.9)2 (2.9)0273
95 (67.9)
8 (5.7)8 (5.7)9 (6.4)1 (0.7)3 (4.3)2 (2.9)5 (3.6)

Data cut-off: Feb 20, 2020.
Except for the Number of Adverse Events subjects are counted only once per treatment in each row.
Serious Adverse Events - according to the investigator's assessment.
(a) Subjects who have an AE record that indicates that the AE caused the subject to be discontinued from the study.
(b) Subjects who have an AE record that indicates that Action Taken with Study Treatment was Drug Withdrawn but AE
did not Cause the Subject to bediscontinued from Study.
MedDRA v22.1 coding dictionary applied.
PFIZER CONFIDENTIAL SDTM Creation: 12MAR2020 (15:21) Source Data: Table 16.2.7.1.1.a
Output File: ./ibd_cdisc/A3921288_pcd/adae_s020 Date of Generation: 15APR2020 (22:07)
Table 14.3.1.2.1.a is for Pfizer internal use.

Conclusion(s):Efficacy

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CLINICAL STUDY REPORT SYNOPSISThe proportion of subjects in modified Mayo remission at Month 6 (primary endpoint)
were 90.0% and 77.1% for the tofacitinib 10 mg BID and tofacitinib 5 mg BID groups,
respectively.

Consistent findings were observed for the secondary efficacy endpoints – remission,
mucosal healing and clinical response.



Observed differences between tofacitinib 10 mg BID and 5 mg BID across efficacy
endpoints at Month 6 were greater in the subgroup with baseline ESS of 1 than thesubgroup with baseline ESS of 0, however the confidence intervals overlap.


Observed differences between tofacitinib 10 mg BID and 5 mg BID across efficacy
endpoints at Month 6 were greater in the prior TNFi treatment failure subgroup than in
the subgroup without prior TNFi treatment failure, however the confidence intervals
overlap.


A higher observed proportion of subjects with an ESS of 0 maintained remission or
achieved other binary efficacy endpoints at Month 6 than the subjects with a baseline
ESS of 1 in the 5 mg BID group (ie, after dose reduction to 5 mg BID).

A slightly higher observed proportion of subjects without prior TNFi failure
maintained remission or achieved other binary efficacy endpoints at Month 6 than thesubjects with prior TNFi failure in the 5 mg BID group (ie, after dose reduction to
5 mg BID).

The biomarker analyses (hsCRP/FCP) performed were generally consistent between
tofacitinib 10 mg BID and tofacitinib 5 mg BID groups.

SafetyThe proportions of subjects with AEs and SAEs were similar between the tofacitinib
10 mg BID and tofacitinib 5 mg BID dose groups.



No deaths were reported in this study.

No new or unexpected safety findings were observed.


Two cardiovascular events were confirmed by adjudication (1 pulmonary embolism
in the tofacitinib 10 mg BID group; 1 cerebrovascular accident in the tofacitinib 5 mg
BID group).



Four herpes zoster events were reported (1 in the tofacitinib 5 mg BID group; 3 in thetofacitinib 10 mg BID group); 1 herpes zoster event was reported in the tofacitinib
10 mg BID group that met criteria for an opportunistic infection (OI). No events
classified as serious herpes zoster.
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Protocol A3921288 (Month 6 Primary Completion)

CLINICAL STUDY REPORT SYNOPSIS

No non-herpes zoster OIs were reported.

One malignancy excluding nonmelanoma skin cancer (NMSC) was confirmed by
adjudication (vulvar cancer in the tofacitinib 5 mg BID group).



One NMSC event was confirmed by adjudication (basal cell carcinoma in thetofacitinib 5 mg BID group).

One hepatic event was adjudicated and assessed as unlikely to be drug induced liver
injury; no potential or confirmed Hy’s Law cases.

No gastrointestinal perforations were reported.

PFIZER CONFIDENTIAL
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