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Clinical Trial Results:
A Phase 2 Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of PF-06823859 in Adult Subjects With Dermatomyositis

Summary
EudraCT number	2020-004228-41
Trial protocol	DE PL HU IT ES
Global end of trial date	28 Nov 2022

Results information
Results version number	v1(current)
This version publication date	12 Jul 2023
First version publication date	12 Jul 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C0251002

ISRCTN number

US NCT number

NCT03181893

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235E 42nd Street, New York, United States, 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Nov 2022

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy, safety, and tolerability of PF 06823859 in participants with moderate to severe DM.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Spain: 2

Country: Number of subjects enrolled

United States: 66

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

32, 9, 16 and 18 subjects were treated in Stage 1, Stage 2, Amended Stage 2 and Stage 3, respectively. A fixed sequence design with crossover at Week 12 was employed in Amended Stage 2 and Stage 3 to provide all subjects with the opportunity to receive active drug during the treatment period.

Screening details

A total of 75 subjects were randomized at 19 centers in 5 countries

Period 1 title

Baseline to Week 12 (All Stages)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo (Stage 1)

Arm description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 1.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo administration took place on Day 1, Week 4 and Week 8 in Stage 1 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

PF-06823859 600 mg intravenous (IV) (Stage 1)

Arm description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.

Arm type

Experimental

Investigational medicinal product name

PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF 06823859 100 mg/mL solution for Injection administered on Day 1, Week4, and Week 8 in Stage 1 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

Placebo (Stage 2)

Arm description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 2.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo administration took place on Day 1, Week 4 and Week 8 in Stage 2 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

PF-06823859 150 mg IV (Stage 2)

Arm description

Subjects in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 in Stage 2.

Arm type

Experimental

Investigational medicinal product name

PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF 06823859 100 mg/mL solution for Injection administered on Day 1, Week4, and Week 8 in Stage 2 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

PF-06823859 600 mg IV (Stage 2)

Arm description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 2.

Arm type

Experimental

Investigational medicinal product name

PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF 06823859 100 mg/mL solution for Injection administered on Day 1, Week4, and Week 8 in Stage 2 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

Placebo then PF-06823859 150 mg IV (Amended Stage 2)

Arm description

Subjects in this group were randomized to placebo then PF-06823859 150 mg in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20. After the treatment period ended at Week 24, subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo or PF-06823859 administration (as dedicated by the treatment sequence) took place on Day 1, Weeks 4, 8, 12, 16 and 20 in Amended Stage 2 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

Placebo then PF-06823859 600 mg IV (Amended Stage 2)

Arm description

Subjects in this group were randomized to placebo then PF-06823859 600 mg in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20. After the treatment period ended at Week 24, subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF-06823859 150 mg IV then Placebo (Amended Stage 2)

Arm description

Subjects in this group were randomized to PF-06823859 150 mg then placebo in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20. After the treatment period ended at Week 24, subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF-06823859 600 mg IV then Placebo (Amended Stage 2)

Arm description

Participants in this group were randomized to PF-06823859 600 mg then placebo in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20 . After the treatment period ended at Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo then PF-06823859 600 mg IV (Stage 3)

Arm description

Subjects in this group were randomized to placebo then PF-06823859 600 mg with a treatment switch at Week 12 in Stage 3. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20. After Week 12, subjects were switched to the other treatment in the sequence. After the treatment period ended at Week 24, subjects entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo or PF-06823859 administration (as dedicated by the treatment sequence) took place on Day 1, Weeks 4, 8, 12, 16 and 20 in Stage 3 over the course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump.

PF-06823859 600 mg IV then placebo (Stage 3)

Arm description

Subjects in this group were randomized to 600 mg PF-06823859 then placebo with a treatment switch at Week 12 in Stage 3. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20. After Week 12, subjects were switched to the other treatment in the sequence. After the treatment period ended at Week 24, subjects entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Started	10	22	1	5	3	2	1	10	3	9	9
Completed	9	20	1	5	3	2	1	10	3	9	9
Not completed	1	2	0	0	0	0	0	0	0	0	0
Consent withdrawn by subject	-	1	-	-	-	-	-	-	-	-	-
Adverse event, non-fatal	1	1	-	-	-	-	-	-	-	-	-

Period 2 title

Weeks 12-24 (Amended Stage 2, Stage 3)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo then PF-06823859 150 mg IV (Amended Stage 2)

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo then PF-06823859 600 mg IV (Amended Stage 2)

Arm description

Subjects in this group were randomized to placebo then PF-06823859 600 mg in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and seek 20. After the treatment period ended at Week 24, Subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF-06823859 150 mg IV then Placebo (Amended Stage 2)

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF-06823859 600 mg IV then Placebo (Amended Stage 2)

Arm description

Subjects in this group were randomized to PF-06823859 600 mg then placebo in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and Week 20 . After the treatment period ended at Week 24, subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo then PF-06823859 600 mg IV (Stage 3)

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

PF-06823859 600 mg IV then placebo (Stage 3)

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo and PF-06823859

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 2 ^[1]	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Started	2	1	10	3	9	9
Completed	2	1	9	2	8	8
Not completed	0	0	1	1	1	1
Consent withdrawn by subject	-	-	-	-	1	-
Adverse event, non-fatal	-	-	-	-	-	1
Unspecified	-	-	1	1	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The number of subjects (2 subjects) started from Week 12 is same as the number of subjects completing the preceding period (2 subjects).

Baseline characteristics

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Reporting group title

Placebo (Stage 1)

Reporting group description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 1.

Reporting group title

PF-06823859 600 mg intravenous (IV) (Stage 1)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.

Reporting group title

Placebo (Stage 2)

Reporting group description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

PF-06823859 150 mg IV (Stage 2)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

PF-06823859 600 mg IV (Stage 2)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

Placebo then PF-06823859 150 mg IV (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Amended Stage 2)

Reporting group description

Reporting group title

PF-06823859 150 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Stage 3)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then placebo (Stage 3)

Reporting group description

Reporting group values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)	Total
Number of subjects	10	22	1	5	3	2	1	10	3	9	9	75
Age Categorical
Units: Participants
18-64 Years	8	18	1	4	2	1	1	8	3	8	8	62
65-84 Years	2	4	0	1	1	1	0	2	0	1	1	13
>=85 Years	0	0	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	50.20 ( 14.054 )	54.41 ( 13.154 )	42.00 ( 99999 )	51.60 ( 15.726 )	45.67 ( 23.714 )	64.00 ( 1.414 )	44 ( 99999 )	53.90 ( 10.999 )	47.00 ( 13.115 )	47.44 ( 12.126 )	42.44 ( 16.697 )	-
Sex: Female, Male
Units: Participants
Female	9	20	1	5	3	2	1	10	2	6	7	66
Male	1	2	0	0	0	0	0	0	1	3	2	9
Race/Ethnicity, Customized
Units: Subjects
White	9	20	1	5	3	2	1	9	3	8	8	69
Black or African American	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	1	0	1	0	2
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0
Other	0	0	0	0	0	0	0	0	0	0	0	0
Multiracial	1	0	0	0	0	0	0	0	0	0	0	1
Not reported	0	2	0	0	0	0	0	0	0	0	1	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	2	2	1	0	1	0	0	1	1	3	2	13
Not Hispanic or Latino	8	20	0	5	2	2	1	9	2	6	7	62
Unknown	0	0	0	0	0	0	0	0	0	0	0	0
Not Reported	0	0	0	0	0	0	0	0	0	0	0	0

End points

Top of page

Reporting group title

Placebo (Stage 1)

Reporting group description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 1.

Reporting group title

PF-06823859 600 mg intravenous (IV) (Stage 1)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.

Reporting group title

Placebo (Stage 2)

Reporting group description

Subjects in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

PF-06823859 150 mg IV (Stage 2)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

PF-06823859 600 mg IV (Stage 2)

Reporting group description

Subjects in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 2.

Reporting group title

Placebo then PF-06823859 150 mg IV (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Amended Stage 2)

Reporting group description

Reporting group title

PF-06823859 150 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Stage 3)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then placebo (Stage 3)

Reporting group description

Reporting group title

Placebo then PF-06823859 150 mg IV (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Amended Stage 2)

Reporting group description

Subjects in this group were randomized to placebo then PF-06823859 600 mg in Amended Stage 2. Study intervention or placebo administration (as dictated by the treatment sequence) occurred on Day 1, Week 4, Week 8, Week 12, Week 16, and seek 20. After the treatment period ended at Week 24, Subjects then entered a 4-month follow-up period or rolled over to the long-term extension study.

Reporting group title

PF-06823859 150 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then Placebo (Amended Stage 2)

Reporting group description

Reporting group title

Placebo then PF-06823859 600 mg IV (Stage 3)

Reporting group description

Reporting group title

PF-06823859 600 mg IV then placebo (Stage 3)

Reporting group description

Primary: Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 12 (Stage 1, Stage 2 and Amended Stage 2)

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End point title

Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 12 (Stage 1, Stage 2 and Amended Stage 2) ^[1]

End point description

The treatment effect was defined as the difference (mean chg from baseline at Week12 in the active treatment group minus that in the placebo group) in the mean change of CDASI activity score from baseline at Week 12. The score (range: 0-100) consists of the extent score (ES), Gottorn hands score (GHS), peringual score (PS) and allopecia score (AS). ES (range: 0-90) was obtained by summing up scores for the total erythema (ER [0-45], redness of the skin or mucous membranes), scaling (SC [0-30], peeling of the skin) and erosion/ulceration (EU [0-15], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule’s characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.

End point type

Primary

End point timeframe

Baseline and Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This is primary endpoint for arms in Stage 1, Stage 2, and amended Stage 2. The statistics for arms in Stage 3 are reported in the secondary endpoint.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	9	21	1	5	3	2	1	10	3
Units: Units on a scale
arithmetic mean (standard deviation)	-3.44 ( 5.270 )	-19.62 ( 9.140 )	5.00 ( 99999 )	-17.40 ( 9.290 )	-26.00 ( 7.937 )	-3.00 ( 8.485 )	3.00 ( 99999 )	-16.40 ( 5.835 )	-15.33 ( 6.028 )

PF-06823859 600 mg vs Placebo (Stage 1)

Comparison groups

Placebo (Stage 1) v PF-06823859 600 mg intravenous (IV) (Stage 1)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001

Method

LANCOVA-P model

Parameter type

Mean difference (final values)

Point estimate

-14.82

Confidence interval

level

90%

sides

2-sided

lower limit

-20.26

upper limit

-9.37

Variability estimate

Standard error of the mean

Dispersion value

3.183

Primary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3) ^[2] ^[3]

End point description

Adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 40 that were absent before treatment or that worsened relative to pretreatment state.

End point type

Primary

End point timeframe

Up to Week 40

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for the safety endpoint.
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Subjects
TEAEs	7	8
SAEs	0	2

No statistical analyses for this end point

Primary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 3)

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End point title

Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 3) ^[4] ^[5]

End point description

Hemoglobin(HGB),hematocrit,erythrocytes(ery.),HDL cholesterol(chl.)<0.8*lower limit of normal(LLN);reticulocytes (ret.), ret./ery.(%)<0.5*LLN,>1.5*upper limit of normal (ULN);ery. mean corpuscular(EMC) volume,EMC HGB concentration,potassium,chloride,calcium,bicarbonate<0.9*LLN,>1.1*ULN;platelets<0.5*LLN,>1.75*ULN; leukocytes(leu.),glucose<0.6*LLN,>1.5*ULN;lymphocytes(lym.), lym./leu.(%),neutrophils (neu.), neu./leu.(%), protein,albumin<0.8*LLN,>1.2*ULN;basophils(bas.), bas./leu.(%), eosinophils(eos.), eos./leu., monocytes(mon.), mon./leu.(%), urate>1.2*ULN;bilirubin (total, direct,indirect)>1.5*ULN;aspartate/alanine aminotransferase,gamma glutamyl transferase,lactate dehydrogenase,alkaline phosphatase>3.0*ULN;urea nitrogen,creatinine,triglycerides, chl.>1.3*ULN; sodium <0.95*LLN,>1.05*ULN; creatine kinase >2.0*ULN;Urine: pH<4.5,>8;glucose, ketones,protein, HGB,urobilinogen,bilirubin,nitrite,leukocyte esterase>=1;ery., leu.>= 20;hyaline casts>1;bacteria>20.

End point type

Primary

End point timeframe

Up to Week 40

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for the safety endpoint.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Subjects	0	1

No statistical analyses for this end point

Primary: Number of Subjects With Vital Sign Abnormalities (Stage 3)

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End point title

Number of Subjects With Vital Sign Abnormalities (Stage 3) ^[6] ^[7]

End point description

Abnormality in vital signs: Sitting pulse rate <40 beats per minute (bpm) to >120 bpm, sitting diastolic blood pressure (DBP) < 50 millimeter of mercury (mmHg), sitting systolic blood pressure (SBP) <90 mmHg.

End point type

Primary

End point timeframe

Baseline up to Week 40

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for the safety endpoint.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Subjects
Sitting SBP Value <90 mmHg	0	0
Sitting DBP Value <50 mmHg	0	0
Sitting Pulse Rate Value <40 bpm	0	0
Sitting Pulse Rate Value >120 bpm	0	0

No statistical analyses for this end point

Primary: Number of Subjects With Electrocardiogram (ECG) Abnormalities (Stage 3)

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End point title

Number of Subjects With Electrocardiogram (ECG) Abnormalities (Stage 3) ^[8] ^[9]

End point description

ECG abnormalities criteria included: 1) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >=30, increase from baseline >=60; 2) Pulse rate (PR) (msec): >=300, change from baseline (Chg) >=25% or 50%; 3) QT (msec): >=500; 4) QRS (msec): >=200, Chg >=25% or 50%. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure.

End point type

Primary

End point timeframe

Baseline up to Week 40

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for the safety endpoint.
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Subjects
PR Interval Aggregate Value >=300 msec	0	0
QRS Duration Aggregate Value >=200 msec	0	0
QT Interval Aggregate Value >=500 msec	0	0
QTcF Interval Aggregate 450<=Value<480 msec	0	1
QTcF Interval Aggregate 480<=Value<500 msec	1	0
QTcF Interval Aggregate Value >=500 msec	0	0
PR %Chg >=25% or >=50%	0	0
QRS Duration %Chg >=25% or >=50%	0	0
30<=QTcF Chg (msec)<60	0	0
QTcF Chg (msec) >=60	0	1

No statistical analyses for this end point

Secondary: Number of Subjects With TEAEs and SAEs (Stage 1 and Stage 2)

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End point title

Number of Subjects With TEAEs and SAEs (Stage 1 and Stage 2) ^[10]

End point description

AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 28 that were absent before treatment or that worsened relative to pretreatment state.

End point type

Secondary

End point timeframe

Up to Week 28

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)
Number of subjects analysed	10	22	1	5	3
Units: Subjects
TEAEs	8	20	1	5	3
SAEs	1	2	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With TEAEs and SAEs (Amended Stage 2)

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End point title

Number of Subjects With TEAEs and SAEs (Amended Stage 2) ^[11]

End point description

AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 40 that were absent before treatment or that worsened relative to pretreatment state.

End point type

Secondary

End point timeframe

Up to Week 40

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	2	1	10	3
Units: Subjects
TEAEs	1	1	8	3
SAEs	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)

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End point title

Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2) ^[12]

End point description

HGB,hematocrit,ery.,HDL chl.<0.8*LLN;ret., ret./ery. (%)<0.5*LLN,>1.5*ULN;EMC volume,EMC HGB,EMC HGB concentration,potassium,chloride,calcium,bicarbonate<0.9*LLN,>1.1*ULN;platelets<0.5*LLN,>1.75*ULN;leu.,glucose<0.6*LLN,>1.5*ULN;lym., lym./leu.(%), neu., neu./leu. (%), protein,albumin <0.8*LLN,>1.2*ULN;bas., bas./leu.(%), eos., eos./leu., mon., mon./leu.(%), urate >1.2*ULN;bilirubin (total, direct, indirect)>1.5*ULN;aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase>3.0*ULN;urea nitrogen, creatinine, triglycerides, chl.>1.3*ULN; sodium <0.95*LLN,>1.05*ULN; creatine kinase >2.0*ULN;Urine: pH<4.5,>8;glucose, ketones, protein, HGB, urobilinogen,bilirubin,nitrite,leukocyte esterase>=1;ery., leu.>= 20;hyaline casts>1;bacteria>20. Clinical significance of laboratory parameters was determined at the investigator's discretion.

End point type

Secondary

End point timeframe

Up to Week 28

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)
Number of subjects analysed	10	22	1	5	3
Units: Subjects	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Amended Stage 2)

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End point title

Number of Subjects With Clinically Significant Laboratory Abnormalities (Amended Stage 2) ^[13]

End point description

End point type

Secondary

End point timeframe

Up to Week 40

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	2	1	10	3
Units: Subjects	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Sign Abnormalities (Stage 1 and Stage 2)

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End point title

Number of Subjects With Vital Sign Abnormalities (Stage 1 and Stage 2) ^[14]

End point description

Abnormality in vital signs: Sitting pulse rate <40 bpm to >120 bpm, sitting DBP < 50 mmHg, sitting SBP <90 mmHg.

End point type

Secondary

End point timeframe

Up to Week 28

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)
Number of subjects analysed	10	22	1	5	3
Units: Subjects
Sitting SBP Value <90 mmHg	0	1	0	0	0
Sitting DBP Value <50 mmHg	0	0	0	0	0
Sitting Pulse Rate Value <40 bpm	0	0	0	0	0
Sitting Pulse Rate Value >120 bpm	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Sign Abnormalities (Amended Stage 2)

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End point title

Number of Subjects With Vital Sign Abnormalities (Amended Stage 2) ^[15]

End point description

Abnormality in vital signs: Sitting pulse rate <40 bpm to >120 bpm, sitting DBP < 50 mmHg, sitting SBP <90 mmHg.

End point type

Secondary

End point timeframe

Up to Week 40

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	2	1	10	3
Units: Subjects
Sitting SBP Value <90 mmHg	0	0	0	0
Sitting DBP Value <50 mmHg	0	0	0	0
Sitting Pulse Rate Value <40 bpm	0	0	0	0
Sitting Pulse Rate Value >120 bpm	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With ECG Abnormalities (Stage 1 and Stage 2)

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End point title

Number of Subjects With ECG Abnormalities (Stage 1 and Stage 2) ^[16]

End point description

End point type

Secondary

End point timeframe

Up to Week 28

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)
Number of subjects analysed	10	22	1	5	3
Units: Subjects
PR Interval Aggregate Value >=300 msec	0	0	0	0	0
QRS Duration Aggregate Value >=200 msec	0	0	0	0	0
QT Interval Aggregate Value >=500 msec	0	0	0	0	0
QTcF Interval Aggregate 450<=Value<480 msec	3	1	0	1	0
QTcF Interval Aggregate 480<=Value<500 msec	0	0	0	0	0
QTcF Interval Aggregate Value >=500 msec	0	1	0	0	0
PR %Chg >=25% or >=50%	0	0	0	0	0
QRS Duration %Chg >=25% or >=50%	0	0	0	0	0
30<=QTcF Chg (msec)<60	0	0	0	0	0
QTcF Chg (msec) >=60	0	1	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With ECG Abnormalities (Amended Stage 2)

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End point title

Number of Subjects With ECG Abnormalities (Amended Stage 2) ^[17]

End point description

End point type

Secondary

End point timeframe

Up to Week 40

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints were reported by stages. All the arms in the baseline period reported statistics.

End point values	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	2	1	10	3
Units: Subjects
PR Interval Aggregate Value >=300 msec	0	0	0	0
QRS Duration Aggregate Value >=200 msec	0	0	0	0
QT Interval Aggregate Value >=500 msec	0	0	0	0
QTcF Interval Aggregate 450<=Value<480 msec	1	0	3	0
QTcF Interval Aggregate 480<=Value<500 msec	0	0	0	0
QTcF Interval Aggregate Value >=500 msec	0	0	0	0
PR %Chg >=25% or >=50%	0	0	0	0
QRS Duration %Chg >=25% or >=50%	0	0	0	0
30<=QTcF Chg (msec)<60	1	0	1	0
QTcF Chg (msec) >=60	0	0	0	0

No statistical analyses for this end point

Secondary: Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2)

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End point title

Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2) ^[18]

End point description

The treatment effect was defined as the difference (mean change from baseline at Weeks 1, 4, 8 in the active treatment group minus the mean change from baseline at Weeks 1, 4, 8 in the placebo group) in the mean change of CDASI activity score from baseline at scheduled timepoints. The score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER [0-45], redness of the skin or mucous membranes), scaling (SC [0-30], peeling of the skin) and erosion/ulceration (EU [0-15], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule’s characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.

End point type

Secondary

End point timeframe

Baseline, Week 1, Week 4, and Week 8 (except for Week 12 which is a primary outcome measure)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Change from baseline in CDASI activity score for arms in Stage 3 was reported in the next end point.

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)
Number of subjects analysed	10	21	1	5	3	2	1	10	3
Units: Units on a scale
arithmetic mean (standard deviation)
Week 1	-2.60 ( 4.326 )	-19.62 ( 9.140 )	1.00 ( 99999 )	-9.80 ( 12.174 )	-2.33 ( 1.528 )	-6.50 ( 6.364 )	0.00 ( 99999 )	-8.70 ( 5.638 )	-6.67 ( 2.517 )
Week 4	-2.44 ( 8.126 )	-12.00 ( 10.277 )	3.00 ( 99999 )	-11.20 ( 10.986 )	-15.00 ( 7.550 )	-3.00 ( 7.071 )	-1.00 ( 99999 )	-14.40 ( 7.648 )	-14.00 ( 2.000 )
Week 8	-4.22 ( 6.942 )	-17.19 ( 9.595 )	4.00 ( 99999 )	-14.20 ( 5.020 )	-18.67 ( 10.066 )	-2.50 ( 7.778 )	-2.00 ( 99999 )	-17.80 ( 7.540 )	-14.00 ( 4.000 )

No statistical analyses for this end point

Secondary: Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)

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End point title

Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3) ^[19]

End point description

The treatment effect was defined as the difference (mean change from baseline at Weeks 1, 4, 8,12 in the active treatment group minus the mean change from baseline at Weeks 1, 4, 8, 12 in the placebo group) in the mean change of CDASI activity score from baseline at scheduled timepoints. The score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER [0-45], redness of the skin or mucous membranes), scaling (SC [0-30], peeling of the skin) and erosion/ulceration (EU [0-15], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule’s characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.

End point type

Secondary

End point timeframe

Baseline, Week 1, Week 4, Week 8 and Week 12

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics for other arms were reported in the previous end point.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Units on a scale
arithmetic mean (standard deviation)
Week 1	-2.00 ( 3.808 )	-2.11 ( 2.522 )
Week 4	-3.78 ( 5.333 )	-5.11 ( 5.555 )
Week 8	-5.00 ( 7.382 )	-7.78 ( 6.667 )
Week 12	-5.89 ( 8.177 )	-8.56 ( 7.923 )

No statistical analyses for this end point

Secondary: Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)

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End point title

Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)

End point description

The CDASI activity score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER [0-45], redness of the skin or mucous membranes), scaling (SC [0-30], peeling of the skin) and erosion/ulceration (EU [0-15], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule’s characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.

End point type

Secondary

End point timeframe

Baseline, Week 1, Week 4, Week 8 and Week 12

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	10	22	1	5	3	2	1	10	3	9	9
Units: Units on a scale
arithmetic mean (standard deviation)
Baseline	31.50 ( 11.750 )	33.23 ( 10.323 )	23.00 ( 99999 )	28.60 ( 9.017 )	37.00 ( 9.644 )	26.00 ( 5.657 )	37.00 ( 99999 )	35.40 ( 13.226 )	30.00 ( 7.937 )	17.22 ( 11.595 )	12.56 ( 8.095 )
Week 1	28.90 ( 12.982 )	27.68 ( 8.962 )	24.00 ( 99999 )	18.80 ( 6.535 )	34.67 ( 9.713 )	19.50 ( 0.707 )	37.00 ( 99999 )	26.70 ( 12.667 )	23.33 ( 9.018 )	15.22 ( 9.846 )	10.44 ( 6.894 )
Week 4	28.11 ( 16.136 )	21.23 ( 11.182 )	26.00 ( 99999 )	17.40 ( 2.408 )	22.00 ( 12.490 )	23.00 ( 1.414 )	36.00 ( 99999 )	21.00 ( 10.677 )	16.00 ( 9.539 )	13.44 ( 8.819 )	7.44 ( 5.503 )
Week 8	26.33 ( 13.892 )	15.29 ( 6.157 )	27.00 ( 99999 )	14.40 ( 5.857 )	18.33 ( 5.508 )	23.50 ( 2.121 )	35.00 ( 99999 )	17.60 ( 10.895 )	16.00 ( 11.269 )	12.22 ( 10.883 )	4.78 ( 4.116 )
Week 12	27.11 ( 14.903 )	12.86 ( 5.876 )	28.00 ( 99999 )	11.20 ( 4.817 )	11.00 ( 3.464 )	23.00 ( 2.828 )	40.00 ( 99999 )	19.00 ( 14.087 )	14.67 ( 9.504 )	11.33 ( 9.206 )	4.00 ( 3.464 )

No statistical analyses for this end point

Secondary: Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)

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End point title

Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)

End point description

The Damage Score (DS) was calculated as a sum of the total poilkiloderma score (POLS), total calcinosis score (CALS) and Gotorn’s hands damage score (GHDS). The POLS characterizes specific dispigmentation in the particulal area and calcinosis score characterizes calcification of the skin in the particular area. The POLS and the CALS are summed up over 15 individual areas in the body and each of them has range 0-15. The GHDS has the range 0-2 so that the DS has the range 0-32.

End point type

Secondary

End point timeframe

Baseline, Week 1, Week 4, Week 8 and Week 12

End point values	Placebo (Stage 1)	PF-06823859 600 mg intravenous (IV) (Stage 1)	Placebo (Stage 2)	PF-06823859 150 mg IV (Stage 2)	PF-06823859 600 mg IV (Stage 2)	Placebo then PF-06823859 150 mg IV (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Amended Stage 2)	PF-06823859 150 mg IV then Placebo (Amended Stage 2)	PF-06823859 600 mg IV then Placebo (Amended Stage 2)	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	10	22	1	5	3	2	1	10	3	9	9
Units: Units on a scale
arithmetic mean (standard deviation)
Baseline	4.30 ( 5.397 )	5.50 ( 3.901 )	3.00 ( 99999 )	4.20 ( 3.701 )	7.00 ( 1.732 )	7.50 ( 4.950 )	7.00 ( 99999 )	4.70 ( 4.373 )	7.00 ( 3.000 )	5.56 ( 6.044 )	2.00 ( 1.871 )
Week 1	4.90 ( 5.021 )	5.41 ( 4.159 )	4.00 ( 99999 )	3.80 ( 3.347 )	6.33 ( 3.215 )	6.00 ( 7.071 )	7.00 ( 99999 )	3.90 ( 3.542 )	4.67 ( 2.887 )	6.00 ( 5.809 )	1.89 ( 1.764 )
Week 4	5.11 ( 5.278 )	5.23 ( 3.337 )	4.00 ( 99999 )	3.00 ( 2.449 )	9.00 ( 1.732 )	7.00 ( 5.657 )	7.00 ( 99999 )	4.40 ( 4.248 )	6.33 ( 1.528 )	5.22 ( 4.631 )	1.56 ( 2.297 )
Week 8	5.89 ( 5.231 )	5.00 ( 4.427 )	5.00 ( 99999 )	4.40 ( 2.881 )	8.33 ( 0.577 )	5.50 ( 3.536 )	7.00 ( 99999 )	3.70 ( 3.945 )	4.67 ( 3.215 )	5.11 ( 4.859 )	1.00 ( 1.118 )
Week 12	6.33 ( 5.679 )	5.05 ( 3.905 )	6.00 ( 99999 )	3.60 ( 3.286 )	6.33 ( 1.528 )	4.50 ( 4.950 )	7.00 ( 99999 )	3.10 ( 4.358 )	5.00 ( 1.000 )	5.22 ( 5.019 )	1.33 ( 1.581 )

No statistical analyses for this end point

Secondary: Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)

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End point title

Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3) ^[20]

End point description

The TIS was the sum of all 6 improvement scores (PhGA [from the MDAAT], PtGA, MMT, HAQ-DI, muscle enzymes, and extramuscular global assessment) associated with the change in each core set measure. A total improvement score of ≥20 represented minimal improvement, a score of ≥40 represented moderate improvement, and a score of ≥60 represented major improvement.

End point type

Secondary

End point timeframe

Week 4, Week 8 and Week 12

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This secondary endpoint is only for arms in Stage 3.

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Units on a scale
least squares mean (confidence interval 90%)
Week 4	25.83 (13.15 to 38.52)	36.67 (23.98 to 49.35)
Week 8	36.67 (23.38 to 49.95)	49.17 (35.88 to 62.45)
Week 12	36.94 (21.93 to 51.96)	56.39 (41.38 to 71.40)

PF-06823859 600 mg vs Placebo at Week 4

Statistical analysis description

Difference of the active treatment from Placebo at Week 4

Comparison groups

Placebo then PF-06823859 600 mg IV (Stage 3) v PF-06823859 600 mg IV then placebo (Stage 3)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[21]

P-value

= 0.1537

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

10.83

Confidence interval

level

90%

sides

2-sided

lower limit

-7.1

upper limit

28.77

Variability estimate

Standard error of the mean

Dispersion value

10.274

Notes
[21] - Subjects in the arm of "Placebo then PF-06823859 600 mg IV (Stage 3)" received placebo on Day 1, Weeks 4, 8 and 12 with a treatment switch to PF-06823859 at Week 12. Subjects in the arm of "PF-06823859 600 mg IV then placebo (Stage 3)" received PF-06823859 on Day 1, Weeks 4, 8 and 12 with a treatment switch to placebo at Week 12.

PF-06823859 600 mg vs Placebo at Week 12

Statistical analysis description

Difference of the active treatment from Placebo at Week 12

Comparison groups

Placebo then PF-06823859 600 mg IV (Stage 3) v PF-06823859 600 mg IV then placebo (Stage 3)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[22]

P-value

= 0.0647

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

19.44

Confidence interval

level

90%

sides

2-sided

lower limit

-1.79

upper limit

40.68

Variability estimate

Standard error of the mean

Dispersion value

12.161

Notes
[22] - Subjects in the arm of "Placebo then PF-06823859 600 mg IV (Stage 3)" received placebo on Day 1, Weeks 4, 8 and 12 with a treatment switch to PF-06823859 at Week 12. Subjects in the arm of "PF-06823859 600 mg IV then placebo (Stage 3)" received PF-06823859 on Day 1, Weeks 4, 8 and 12 with a treatment switch to placebo at Week 12.

PF-06823859 600 mg vs Placebo at Week 8

Statistical analysis description

Difference of the active treatment from Placebo at Week 8

Comparison groups

Placebo then PF-06823859 600 mg IV (Stage 3) v PF-06823859 600 mg IV then placebo (Stage 3)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[23]

P-value

= 0.1312

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

12.5

Confidence interval

level

90%

sides

2-sided

lower limit

-6.29

upper limit

31.29

Variability estimate

Standard error of the mean

Dispersion value

10.761

Notes
[23] - Subjects in the arm of "Placebo then PF-06823859 600 mg IV (Stage 3)" received placebo on Day 1, Weeks 4, 8 and 12 with a treatment switch to PF-06823859 at Week 12. Subjects in the arm of "PF-06823859 600 mg IV then placebo (Stage 3)" received PF-06823859 on Day 1, Weeks 4, 8 and 12 with a treatment switch to placebo at Week 12.

Secondary: Change From Baseline in the Core Set Measures (CSM) of the TIS (Stage 3)

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End point title

Change From Baseline in the Core Set Measures (CSM) of the TIS (Stage 3)

End point description

End point type

Secondary

End point timeframe

Week 4, Week 8 and Week 12

End point values	Placebo then PF-06823859 600 mg IV (Stage 3)	PF-06823859 600 mg IV then placebo (Stage 3)
Number of subjects analysed	9	9
Units: Units on a scale
least squares mean (confidence interval 90%)
PhGA (CM) Week 4	-1.00 (-1.89 to -0.11)	-1.68 (-2.57 to -0.79)
PhGA (CM) Week 8	-1.65 (-2.80 to -0.51)	-2.76 (-3.90 to -1.61)
PhGA (CM) Week 12	-2.05 (-3.56 to -0.55)	-3.40 (-4.90 to -1.90)
PtGA Week 4	-18.29 (-31.78 to -4.79)	-17.88 (-30.75 to -5.00)
PtGA Week 8	-16.81 (-29.88 to -3.73)	-32.60 (-45.85 to -19.35)
PtGA Week 12	-14.04 (-25.91 to -2.17)	-43.81 (-55.68 to -31.95)
MMT8 Total Score - Derived Week 4	7.76 (1.37 to 14.16)	8.24 (1.84 to 14.63)
MMT8 Total Score - Derived Week 8	12.14 (4.60 to 19.68)	15.24 (7.70 to 22.78)
MMT8 Total Score - Derived Week 12	11.65 (2.29 to 21.01)	21.24 (11.87 to 30.60)
HAQ01-HAQ-DI Score Week 4	-0.03 (-0.24 to 0.18)	-0.20 (-0.39 to 0.00)
HAQ01-HAQ-DI Score Week 8	0.00 (-0.28 to 0.28)	-0.38 (-0.64 to -0.11)
HAQ01-HAQ-DI Score Week 12	-0.06 (-0.40 to 0.28)	-0.52 (-0.84 to -0.19)
Extramuscular Global Assessment Week 4	-1.02 (-2.07 to 0.03)	-1.55 (-2.60 to -0.49)
Extramuscular Global Assessment Week 8	-1.91 (-2.80 to -1.01)	-2.48 (-3.38 to -1.58)
Extramuscular Global Assessment Week 12	-1.59 (-2.64 to -0.53)	-2.81 (-3.87 to -1.76)
Aldolase (U/L) Week 4	-0.19 (-1.34 to 0.96)	-3.09 (-4.25 to -1.92)
Aldolase (U/L) Week 8	-1.31 (-2.45 to -0.16)	-3.57 (-4.74 to -2.40)
Aldolase (U/L) Week 12	-0.66 (-2.18 to 0.86)	-3.20 (-4.76 to -1.64)
Creatine Kinase (U/L) Week 4	-37.96 (-119.16 to 43.24)	-157.48 (-238.68 to -76.28)
Creatine Kinase (U/L) Week 8	-70.96 (-137.03 to -4.90)	-175.93 (-241.99 to -109.86)
Creatine Kinase (U/L) Week 12	-39.85 (-125.71 to 46.01)	-185.77 (-273.92 to -97.62)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to Week 40

Adverse event reporting additional description

The safety analysis set includes all participants who received at least one dose of randomized treatment in any stage. The AEs reported were treatment emergent.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Placebo

Reporting group description

Participants who received placebo in any stage.

Reporting group title

Total

Reporting group description

Treatment Group Description TBD

Reporting group title

PF-06823859 600 mg IV

Reporting group description

Participants who received PF-06823859 600 mg IV in any stage.

Reporting group title

PF-06823859 150 mg IV

Reporting group description

Participants who received PF-06823859 150 mg IV in any stage.

Serious adverse events	Placebo	Total	PF-06823859 600 mg IV	PF-06823859 150 mg IV
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 45 (6.67%)	5 / 75 (6.67%)	4 / 47 (8.51%)	0 / 17 (0.00%)
number of deaths (all causes)	1	1	1	0
number of deaths resulting from adverse events	1	1	0	0
Investigations
Blood bilirubin increased
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Humerus fracture
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	1 / 47 (2.13%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Central nervous system lesion
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Cytopenia
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	1 / 47 (2.13%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Haemophagocytic lymphohistiocytosis
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
Gastrointestinal disorders
Colitis microscopic
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	1 / 47 (2.13%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Ocular icterus
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	1 / 47 (2.13%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Total	PF-06823859 600 mg IV	PF-06823859 150 mg IV
Total subjects affected by non serious adverse events
subjects affected / exposed	22 / 45 (48.89%)	45 / 75 (60.00%)	18 / 47 (38.30%)	13 / 17 (76.47%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 45 (8.89%)	6 / 75 (8.00%)	1 / 47 (2.13%)	1 / 17 (5.88%)
occurrences all number	4	6	1	1
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
subjects affected / exposed	0 / 45 (0.00%)	2 / 75 (2.67%)	1 / 47 (2.13%)	1 / 17 (5.88%)
occurrences all number	0	2	1	1
Investigations
Blood potassium decreased
subjects affected / exposed	0 / 45 (0.00%)	2 / 75 (2.67%)	1 / 47 (2.13%)	1 / 17 (5.88%)
occurrences all number	0	2	1	1
SARS-CoV-2 test positive
subjects affected / exposed	4 / 45 (8.89%)	4 / 75 (5.33%)	1 / 47 (2.13%)	0 / 17 (0.00%)
occurrences all number	4	4	1	0
Weight increased
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	1	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 45 (0.00%)	3 / 75 (4.00%)	2 / 47 (4.26%)	1 / 17 (5.88%)
occurrences all number	0	3	2	1
Infusion related reaction
subjects affected / exposed	2 / 45 (4.44%)	2 / 75 (2.67%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	2	2	0	1
Skin laceration
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	1	0	1
Nervous system disorders
Headache
subjects affected / exposed	7 / 45 (15.56%)	15 / 75 (20.00%)	6 / 47 (12.77%)	3 / 17 (17.65%)
occurrences all number	8	20	9	3
Hypoaesthesia
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Mental impairment
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 45 (4.44%)	5 / 75 (6.67%)	3 / 47 (6.38%)	0 / 17 (0.00%)
occurrences all number	2	5	3	0
Diarrhoea
subjects affected / exposed	0 / 45 (0.00%)	4 / 75 (5.33%)	3 / 47 (6.38%)	1 / 17 (5.88%)
occurrences all number	0	4	3	1
Abdominal pain
subjects affected / exposed	0 / 45 (0.00%)	2 / 75 (2.67%)	1 / 47 (2.13%)	1 / 17 (5.88%)
occurrences all number	0	2	1	1
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	5 / 45 (11.11%)	6 / 75 (8.00%)	1 / 47 (2.13%)	1 / 17 (5.88%)
occurrences all number	5	6	1	1
Rosacea
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Alopecia
subjects affected / exposed	1 / 45 (2.22%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	1	0	1
Dermatomyositis
subjects affected / exposed	1 / 45 (2.22%)	2 / 75 (2.67%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	2	0	1
Musculoskeletal and connective tissue disorders
Neck pain
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Myalgia
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Arthralgia
subjects affected / exposed	1 / 45 (2.22%)	5 / 75 (6.67%)	3 / 47 (6.38%)	2 / 17 (11.76%)
occurrences all number	1	5	3	2
Infections and infestations
Sinusitis
subjects affected / exposed	3 / 45 (6.67%)	4 / 75 (5.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	4	5	0	1
Tooth abscess
subjects affected / exposed	0 / 45 (0.00%)	1 / 75 (1.33%)	0 / 47 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	1	0	1
Upper respiratory tract infection
subjects affected / exposed	1 / 45 (2.22%)	5 / 75 (6.67%)	4 / 47 (8.51%)	0 / 17 (0.00%)
occurrences all number	1	6	5	0

More information

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Were there any global substantial amendments to the protocol? Yes

20 Sep 2021

The overall rationale for the amendment is to permit participants actively enrolled in the C0251002 study to have the option to continue active treatment into a long term open label extension study, known as protocol C0251008.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2 Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of PF-06823859 in Adult Subjects With Dermatomyositis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 12 (Stage 1, Stage 2 and Amended Stage 2)

Primary: Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 12 (Stage 1, Stage 2 and Amended Stage 2)

Primary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)

Primary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)

Primary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 3)

Primary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 3)

Primary: Number of Subjects With Vital Sign Abnormalities (Stage 3)

Primary: Number of Subjects With Vital Sign Abnormalities (Stage 3)

Primary: Number of Subjects With Electrocardiogram (ECG) Abnormalities (Stage 3)

Primary: Number of Subjects With Electrocardiogram (ECG) Abnormalities (Stage 3)

Secondary: Number of Subjects With TEAEs and SAEs (Stage 1 and Stage 2)

Secondary: Number of Subjects With TEAEs and SAEs (Stage 1 and Stage 2)

Secondary: Number of Subjects With TEAEs and SAEs (Amended Stage 2)

Secondary: Number of Subjects With TEAEs and SAEs (Amended Stage 2)

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Amended Stage 2)

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities (Amended Stage 2)

Secondary: Number of Subjects With Vital Sign Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With Vital Sign Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With Vital Sign Abnormalities (Amended Stage 2)

Secondary: Number of Subjects With Vital Sign Abnormalities (Amended Stage 2)

Secondary: Number of Subjects With ECG Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With ECG Abnormalities (Stage 1 and Stage 2)

Secondary: Number of Subjects With ECG Abnormalities (Amended Stage 2)

Secondary: Number of Subjects With ECG Abnormalities (Amended Stage 2)

Secondary: Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2)

Secondary: Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2)

Secondary: Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)

Secondary: Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)

Secondary: Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)

Secondary: Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)

Secondary: Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)

Secondary: Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)

Secondary: Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)

Secondary: Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)

Secondary: Change From Baseline in the Core Set Measures (CSM) of the TIS (Stage 3)

Secondary: Change From Baseline in the Core Set Measures (CSM) of the TIS (Stage 3)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2 Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of PF-06823859 in Adult Subjects With Dermatomyositis