Trial Outcomes & Findings for A Study In Adults With Moderate To Severe Dermatomyositis (NCT NCT03181893)

Last Updated: 2023-09-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

75 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2023-09-14

Participant Flow

A total of 75 participants were randomized at 19 centers in 5 countries: 32, 9, 16 and 18 participants 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 participants with the opportunity to receive active drug during the treatment period.

Participant milestones

Participant milestones
Measure	(Stage 1) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 1 After week 12, participants went into a follow up period.	(Stage 1) PF-06823859 600 mg Intravenous (IV) Participants in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1. After week 12, participants went into a follow up period.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 2. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Baseline to Week 12 (All Stages) STARTED	10	22	1	5	3	2	1	10	3	9	9
Baseline to Week 12 (All Stages) COMPLETED	9	20	1	5	3	2	1	10	3	9	9
Baseline to Week 12 (All Stages) NOT COMPLETED	1	2	0	0	0	0	0	0	0	0	0
Weeks 12-24 (Amended Stage 2, Stage 3) STARTED	0	0	0	0	0	2	1	10	3	9	9
Weeks 12-24 (Amended Stage 2, Stage 3) COMPLETED	0	0	0	0	0	2	1	9	2	8	8
Weeks 12-24 (Amended Stage 2, Stage 3) NOT COMPLETED	0	0	0	0	0	0	0	1	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	(Stage 1) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8 in Stage 1 After week 12, participants went into a follow up period.	(Stage 1) PF-06823859 600 mg Intravenous (IV) Participants in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1. After week 12, participants went into a follow up period.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Baseline to Week 12 (All Stages) Withdrawal by Subject	0	1	0	0	0	0
Baseline to Week 12 (All Stages) Adverse Event	1	1	0	0	0	0
Weeks 12-24 (Amended Stage 2, Stage 3) Other	0	0	1	1	0	0
Weeks 12-24 (Amended Stage 2, Stage 3) Withdrawal by Subject	0	0	0	0	1	0
Weeks 12-24 (Amended Stage 2, Stage 3) Adverse Event	0	0	0	0	0	1

Baseline Characteristics

A Study In Adults With Moderate To Severe Dermatomyositis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 1) PF-06823859 600 mg Intravenous (IV) n=22 Participants Participants in this group were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 n=2 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=1 Participants Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 n=10 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=3 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	Total n=75 Participants Total of all reporting groups
Age, Continuous	50.20 years STANDARD_DEVIATION 14.054 • n=5 Participants	54.41 years STANDARD_DEVIATION 13.154 • n=7 Participants	42.00 years n=5 Participants	51.60 years STANDARD_DEVIATION 15.726 • n=4 Participants	45.67 years STANDARD_DEVIATION 23.714 • n=21 Participants	64.00 years STANDARD_DEVIATION 1.414 • n=8 Participants	44 years n=8 Participants	53.90 years STANDARD_DEVIATION 10.999 • n=24 Participants	47.00 years STANDARD_DEVIATION 13.115 • n=42 Participants	47.44 years STANDARD_DEVIATION 12.126 • n=42 Participants	42.44 years STANDARD_DEVIATION 16.697 • n=42 Participants	50.63 years STANDARD_DEVIATION 13.793 • n=42 Participants
Age, Customized 18-64 Years	8 Participants n=5 Participants	18 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	8 Participants n=24 Participants	3 Participants n=42 Participants	8 Participants n=42 Participants	8 Participants n=42 Participants	62 Participants n=42 Participants
Age, Customized 65-84 Years	2 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	13 Participants n=42 Participants
Age, Customized >=85 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	20 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	10 Participants n=24 Participants	2 Participants n=42 Participants	6 Participants n=42 Participants	7 Participants n=42 Participants	66 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	9 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	13 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	20 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	9 Participants n=24 Participants	2 Participants n=42 Participants	6 Participants n=42 Participants	7 Participants n=42 Participants	62 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	20 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	9 Participants n=24 Participants	3 Participants n=42 Participants	8 Participants n=42 Participants	8 Participants n=42 Participants	69 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Multiracial	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set (FAS) in Stage 1, Stage 2, and Amended Stage 2 included all participants who received at least 1 dose of randomized treatment in in Stage 1, Stage 2, or Amended Stage 2.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=21 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 n=2 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=1 Participants Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 n=10 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=3 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
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)	-3.44 Units on a scale Standard Deviation 5.270	-19.62 Units on a scale Standard Deviation 9.140	5.00 Units on a scale	-17.40 Units on a scale Standard Deviation 9.290	-26.00 Units on a scale Standard Deviation 7.937	-3.00 Units on a scale Standard Deviation 8.485	3.00 Units on a scale	-16.40 Units on a scale Standard Deviation 5.835	-15.33 Units on a scale Standard Deviation 6.028	—	—

PRIMARY outcome

Timeframe: Up to Week 40

Population: The safety analysis set in Stage 3 (SAS3) included all participants who received at least 1 dose of randomized treatment in Stage 3.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3) TEAEs	7 Participants	8 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3) SAEs	0 Participants	2 Participants	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Week 40

Population: The safety analysis set in Stage 3 (SAS3) included all participants who received at least 1 dose of randomized treatment in Stage 3.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 3)	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline up to Week 40

Population: The SAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Vital Sign Abnormalities (Stage 3) Sitting SBP Value <90 mmHg	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 3) Sitting DBP Value <50 mmHg	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 3) Sitting Pulse Rate Value <40 bpm	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 3) Sitting Pulse Rate Value >120 bpm	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline up to Week 40

Population: The SAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) PR Interval Aggregate Value >=300 msec	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QRS Duration Aggregate Value >=200 msec	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QT Interval Aggregate Value >=500 msec	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QTcF Interval Aggregate 450<=Value<480 msec	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QTcF Interval Aggregate 480<=Value<500 msec	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QTcF Interval Aggregate Value >=500 msec	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) PR %Chg >=25% or >=50%	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QRS Duration %Chg >=25% or >=50%	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) 30<=QTcF Chg (msec)<60	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3) QTcF Chg (msec) >=60	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 28

Population: The safety analysis set in Stage 1 (SAS1) and safety analysis set in Stage 2 (SAS2) included all participants who received at least 1 dose of randomized treatment in Stage 1 and Stage 2, respectively.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With TEAEs and SAEs (Stage 1 and Stage 2) TEAEs	8 Participants	20 Participants	1 Participants	5 Participants	3 Participants	—	—	—	—	—	—
Number of Participants With TEAEs and SAEs (Stage 1 and Stage 2) SAEs	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 40

Population: The safety analysis set in Amended Stage 2 (SASA2) includes all participants who received at least one dose of randomized treatment in Amended Stage 2.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=2 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=1 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=3 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With TEAEs and SAEs (Amended Stage 2) SAEs	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With TEAEs and SAEs (Amended Stage 2) TEAEs	1 Participants	1 Participants	8 Participants	3 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 28

Population: The SAS1 and SAS2 included all participants who received at least 1 dose of randomized treatment in Stage 1 and Stage 2, respectively.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 40

Population: The SASA2 includes all participants who received at least one dose of randomized treatment in Amended Stage 2.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=2 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=1 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=3 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Clinically Significant Laboratory Abnormalities (Amended Stage 2)	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 28

Population: The SAS1 and SAS2 included all participants who received at least 1 dose of randomized treatment in Stage 1 and Stage 2, respectively.

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

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2) Sitting SBP Value <90 mmHg	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2) Sitting DBP Value <50 mmHg	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2) Sitting Pulse Rate Value <40 bpm	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2) Sitting Pulse Rate Value >120 bpm	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 40

Population: The SASA2 includes all participants who received at least one dose of randomized treatment in Amended Stage 2.

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

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=2 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=1 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=3 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With Vital Sign Abnormalities (Amended Stage 2) Sitting SBP Value <90 mmHg	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Amended Stage 2) Sitting DBP Value <50 mmHg	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Amended Stage 2) Sitting Pulse Rate Value <40 bpm	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With Vital Sign Abnormalities (Amended Stage 2) Sitting Pulse Rate Value >120 bpm	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 28

Population: The SAS1 and SAS2 included all participants who received at least 1 dose of randomized treatment in Stage 1 and Stage 2, respectively.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) PR Interval Aggregate Value >=300 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QRS Duration Aggregate Value >=200 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QT Interval Aggregate Value >=500 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QTcF Interval Aggregate 450<=Value<480 msec	3 Participants	1 Participants	0 Participants	1 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QTcF Interval Aggregate 480<=Value<500 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QTcF Interval Aggregate Value >=500 msec	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) PR %Chg >=25% or >=50%	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QRS Duration %Chg >=25% or >=50%	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) 30<=QTcF Chg (msec)<60	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2) QTcF Chg (msec) >=60	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 40

Population: The SASA2 includes all participants who received at least one dose of randomized treatment in Amended Stage 2.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=2 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=1 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=3 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Number of Participants With ECG Abnormalities (Amended Stage 2) PR Interval Aggregate Value >=300 msec	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QRS Duration Aggregate Value >=200 msec	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QT Interval Aggregate Value >=500 msec	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QTcF Interval Aggregate 450<=Value<480 msec	1 Participants	0 Participants	3 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QTcF Interval Aggregate 480<=Value<500 msec	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QTcF Interval Aggregate Value >=500 msec	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) PR %Chg >=25% or >=50%	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QRS Duration %Chg >=25% or >=50%	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) 30<=QTcF Chg (msec)<60	1 Participants	0 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—
Number of Participants With ECG Abnormalities (Amended Stage 2) QTcF Chg (msec) >=60	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—

SECONDARY outcome

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

Population: The FAS in Stage 1, Stage 2, and Amended Stage 2 included all participants who received at least 1 dose of randomized treatment in in Stage 1, Stage 2, or Amended Stage 2.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=21 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 n=2 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=1 Participants Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 n=10 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=3 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2) Week 1	-2.60 Units on a scale Standard Deviation 4.326	-19.62 Units on a scale Standard Deviation 9.140	1.00 Units on a scale	-9.80 Units on a scale Standard Deviation 12.174	-2.33 Units on a scale Standard Deviation 1.528	-6.50 Units on a scale Standard Deviation 6.364	0.00 Units on a scale	-8.70 Units on a scale Standard Deviation 5.638	-6.67 Units on a scale Standard Deviation 2.517	—	—
Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2) Week 4	-2.44 Units on a scale Standard Deviation 8.126	-12.00 Units on a scale Standard Deviation 10.277	3.00 Units on a scale	-11.20 Units on a scale Standard Deviation 10.986	-15.00 Units on a scale Standard Deviation 7.550	-3.00 Units on a scale Standard Deviation 7.071	-1.00 Units on a scale	-14.40 Units on a scale Standard Deviation 7.648	-14.00 Units on a scale Standard Deviation 2.000	—	—
Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2) Week 8	-4.22 Units on a scale Standard Deviation 6.942	-17.19 Units on a scale Standard Deviation 9.595	4.00 Units on a scale	-14.20 Units on a scale Standard Deviation 5.020	-18.67 Units on a scale Standard Deviation 10.066	-2.50 Units on a scale Standard Deviation 7.778	-2.00 Units on a scale	-17.80 Units on a scale Standard Deviation 7.540	-14.00 Units on a scale Standard Deviation 4.000	—	—

SECONDARY outcome

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

Population: The Full Analysis Set in Stage 3 (FAS3) included all participants who received at least 1 dose of randomized treatment in Stage 3.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3) Week 1	-2.00 Units on a scale Standard Deviation 3.808	-2.11 Units on a scale Standard Deviation 2.522	—	—	—	—	—	—	—	—	—
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3) Week 4	-3.78 Units on a scale Standard Deviation 5.333	-5.11 Units on a scale Standard Deviation 5.555	—	—	—	—	—	—	—	—	—
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3) Week 8	-5.00 Units on a scale Standard Deviation 7.382	-7.78 Units on a scale Standard Deviation 6.667	—	—	—	—	—	—	—	—	—
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3) Week 12	-5.89 Units on a scale Standard Deviation 8.177	-8.56 Units on a scale Standard Deviation 7.923	—	—	—	—	—	—	—	—	—

SECONDARY outcome

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

Population: The FAS included all participants who received at least 1 dose of randomized treatment in any study stage.

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.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 n=2 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=1 Participants Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 n=10 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=3 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages) Baseline	31.50 Units on a scale Standard Deviation 11.750	33.23 Units on a scale Standard Deviation 10.323	23.00 Units on a scale	28.60 Units on a scale Standard Deviation 9.017	37.00 Units on a scale Standard Deviation 9.644	26.00 Units on a scale Standard Deviation 5.657	37.00 Units on a scale	35.40 Units on a scale Standard Deviation 13.226	30.00 Units on a scale Standard Deviation 7.937	17.22 Units on a scale Standard Deviation 11.595	12.56 Units on a scale Standard Deviation 8.095
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 1	28.90 Units on a scale Standard Deviation 12.982	27.68 Units on a scale Standard Deviation 8.962	24.00 Units on a scale	18.80 Units on a scale Standard Deviation 6.535	34.67 Units on a scale Standard Deviation 9.713	19.50 Units on a scale Standard Deviation 0.707	37.00 Units on a scale	26.70 Units on a scale Standard Deviation 12.667	23.33 Units on a scale Standard Deviation 9.018	15.22 Units on a scale Standard Deviation 9.846	10.44 Units on a scale Standard Deviation 6.894
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 4	28.11 Units on a scale Standard Deviation 16.136	21.23 Units on a scale Standard Deviation 11.182	26.00 Units on a scale	17.40 Units on a scale Standard Deviation 2.408	22.00 Units on a scale Standard Deviation 12.490	23.00 Units on a scale Standard Deviation 1.414	36.00 Units on a scale	21.00 Units on a scale Standard Deviation 10.677	16.00 Units on a scale Standard Deviation 9.539	13.44 Units on a scale Standard Deviation 8.819	7.44 Units on a scale Standard Deviation 5.503
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 8	26.33 Units on a scale Standard Deviation 13.892	15.29 Units on a scale Standard Deviation 6.157	27.00 Units on a scale	14.40 Units on a scale Standard Deviation 5.857	18.33 Units on a scale Standard Deviation 5.508	23.50 Units on a scale Standard Deviation 2.121	35.00 Units on a scale	17.60 Units on a scale Standard Deviation 10.895	16.00 Units on a scale Standard Deviation 11.269	12.22 Units on a scale Standard Deviation 10.883	4.78 Units on a scale Standard Deviation 4.116
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 12	27.11 Units on a scale Standard Deviation 14.903	12.86 Units on a scale Standard Deviation 5.876	28.00 Units on a scale	11.20 Units on a scale Standard Deviation 4.817	11.00 Units on a scale Standard Deviation 3.464	23.00 Units on a scale Standard Deviation 2.828	40.00 Units on a scale	19.00 Units on a scale Standard Deviation 14.087	14.67 Units on a scale Standard Deviation 9.504	11.33 Units on a scale Standard Deviation 9.206	4.00 Units on a scale Standard Deviation 3.464

SECONDARY outcome

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

Population: The FAS included all participants who received at least 1 dose of randomized treatment in any study stage.

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. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=10 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=22 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo n=1 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV n=5 Participants Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV n=3 Participants Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 n=2 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=1 Participants Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 n=10 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=3 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 n=9 Participants Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages) Baseline	4.30 Units on a scale Standard Deviation 5.397	5.50 Units on a scale Standard Deviation 3.901	3.00 Units on a scale	4.20 Units on a scale Standard Deviation 3.701	7.00 Units on a scale Standard Deviation 1.732	7.50 Units on a scale Standard Deviation 4.950	7.00 Units on a scale	4.70 Units on a scale Standard Deviation 4.373	7.00 Units on a scale Standard Deviation 3.000	5.56 Units on a scale Standard Deviation 6.044	2.00 Units on a scale Standard Deviation 1.871
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 1	4.90 Units on a scale Standard Deviation 5.021	5.41 Units on a scale Standard Deviation 4.159	4.00 Units on a scale	3.80 Units on a scale Standard Deviation 3.347	6.33 Units on a scale Standard Deviation 3.215	6.00 Units on a scale Standard Deviation 7.071	7.00 Units on a scale	3.90 Units on a scale Standard Deviation 3.542	4.67 Units on a scale Standard Deviation 2.887	6.00 Units on a scale Standard Deviation 5.809	1.89 Units on a scale Standard Deviation 1.764
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 4	5.11 Units on a scale Standard Deviation 5.278	5.23 Units on a scale Standard Deviation 3.337	4.00 Units on a scale	3.00 Units on a scale Standard Deviation 2.449	9.00 Units on a scale Standard Deviation 1.732	7.00 Units on a scale Standard Deviation 5.657	7.00 Units on a scale	4.40 Units on a scale Standard Deviation 4.248	6.33 Units on a scale Standard Deviation 1.528	5.22 Units on a scale Standard Deviation 4.631	1.56 Units on a scale Standard Deviation 2.297
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 8	5.89 Units on a scale Standard Deviation 5.231	5.00 Units on a scale Standard Deviation 4.427	5.00 Units on a scale	4.40 Units on a scale Standard Deviation 2.881	8.33 Units on a scale Standard Deviation 0.577	5.50 Units on a scale Standard Deviation 3.536	7.00 Units on a scale	3.70 Units on a scale Standard Deviation 3.945	4.67 Units on a scale Standard Deviation 3.215	5.11 Units on a scale Standard Deviation 4.859	1.00 Units on a scale Standard Deviation 1.118
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages) Week 12	6.33 Units on a scale Standard Deviation 5.679	5.05 Units on a scale Standard Deviation 3.905	6.00 Units on a scale	3.60 Units on a scale Standard Deviation 3.286	6.33 Units on a scale Standard Deviation 1.528	4.50 Units on a scale Standard Deviation 4.950	7.00 Units on a scale	3.10 Units on a scale Standard Deviation 4.358	5.00 Units on a scale Standard Deviation 1.000	5.22 Units on a scale Standard Deviation 5.019	1.33 Units on a scale Standard Deviation 1.581

SECONDARY outcome

Timeframe: Week 4, Week 8 and Week 12

Population: The FAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

The TIS was the sum of all 6 improvement scores where higher score indicates worse status (PhGA \[from the MDAAT, 0-20 scale\], PtGA \[0-10 scale\], MMT \[0-35 scale\], HAQ-DI \[0-10 scale\], muscle enzymes \[0-7.5 scale\], and extramuscular global assessment \[0-20 scale\]) associated with the change in each core set measure. A total improvement score between 0 and 100 corresponded to the degree of improvement, with higher scores corresponding to a greater degree of improvement: of ≥20 represented minimal improvement, a score of ≥40 represented moderate improvement, and a score of ≥60 represented major improvement.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3) Week 4	25.83 Units on a scale Interval 13.15 to 38.52	36.67 Units on a scale Interval 23.98 to 49.35	—	—	—	—	—	—	—	—	—
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3) Week 8	36.67 Units on a scale Interval 23.38 to 49.95	49.17 Units on a scale Interval 35.88 to 62.45	—	—	—	—	—	—	—	—	—
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3) Week 12	36.94 Units on a scale Interval 21.93 to 51.96	56.39 Units on a scale Interval 41.38 to 71.4	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8 and Week 12

Population: The Full Analysis Set in Stage 3 (FAS3) included all participants who received at least 1 dose of randomized treatment in Stage 3.

PhGA: assessment of the severity of disease by the physician. The physician used the visual analog scale and put a mark on 0 cm (best) -10 cm (worst) scale where higher score indicated worse status. EmGA: overall evaluation of disease activity in all extramuscular systems using visual analog scale 0 cm (best) -10 cm (worst) scale where higher score indicated worse status.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) PhGA Week 4	-1.00 Centimeter (cm) Interval -1.89 to -0.11	-1.68 Centimeter (cm) Interval -2.57 to -0.79	—	—	—	—	—	—	—	—	—
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) PhGA Week 8	-1.65 Centimeter (cm) Interval -2.8 to -0.51	-2.76 Centimeter (cm) Interval -3.9 to -1.61	—	—	—	—	—	—	—	—	—
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) PhGA Week 12	-2.05 Centimeter (cm) Interval -3.56 to -0.55	-3.40 Centimeter (cm) Interval -4.9 to -1.9	—	—	—	—	—	—	—	—	—
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) Extramuscular Global Assessment Week 4	-1.02 Centimeter (cm) Interval -2.07 to 0.03	-1.55 Centimeter (cm) Interval -2.6 to -0.49	—	—	—	—	—	—	—	—	—
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) Extramuscular Global Assessment Week 8	-1.91 Centimeter (cm) Interval -2.8 to -1.01	-2.48 Centimeter (cm) Interval -3.38 to -1.58	—	—	—	—	—	—	—	—	—
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3) Extramuscular Global Assessment Week 12	-1.59 Centimeter (cm) Interval -2.64 to -0.53	-2.81 Centimeter (cm) Interval -3.87 to -1.76	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8 and Week 12

Population: The FAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

PtGA: assessment of the severity of disease by the participant/participant's guardian, using a visual analog scale from 0 mm (no evidence of disease activity) to 100 mm (extremely active or severe disease activity). Higher score indicated worse status.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3) PtGA Week 4	-18.29 Millimeter (mm) Interval -31.78 to -4.79	-17.88 Millimeter (mm) Interval -30.75 to -5.0	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3) PtGA Week 8	-16.81 Millimeter (mm) Interval -29.88 to -3.73	-32.60 Millimeter (mm) Interval -45.85 to -19.35	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3) PtGA Week 12	-14.04 Millimeter (mm) Interval -25.91 to -2.17	-43.81 Millimeter (mm) Interval -55.68 to -31.95	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 4, Week 8 and Week 12

Population: The FAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

Manual Muscle Testing-8 designated muscle groups (MMT-8): was a set of 8 designated muscles tested unilaterally generally on right side (left side used unless right side cannot be used). Potential score range was from 0 to 80, where higher scores denoted better health status. HAQ-DI: contained eight sections (including dressing \& grooming, arising, eating, walking, hygiene, grip, reach, and activities). Each section had multiple questions that the participant used to rank their functionality and ranged from 0 to 3 where 0 = without any difficulty and 3 = unable to do. For each participant, the average ranking was calculated for each of the eight sections. HAQ-DI had a score range of 0 to 3, where higher score reflected worse status.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) MMT8 - Derived Week 4	7.76 Units on a scale Interval 1.37 to 14.16	8.24 Units on a scale Interval 1.84 to 14.63	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) MMT8 - Derived Week 8	12.14 Units on a scale Interval 4.6 to 19.68	15.24 Units on a scale Interval 7.7 to 22.78	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) MMT8 - Derived Week 12	11.65 Units on a scale Interval 2.29 to 21.01	21.24 Units on a scale Interval 11.87 to 30.6	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) HAQ01-HAQ-DI Week 4	-0.03 Units on a scale Interval -0.24 to 0.18	-0.20 Units on a scale Interval -0.39 to 0.0	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) HAQ01-HAQ-DI Week 8	0.00 Units on a scale Interval -0.28 to 0.28	-0.38 Units on a scale Interval -0.64 to -0.11	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3) HAQ01-HAQ-DI Week 12	-0.06 Units on a scale Interval -0.4 to 0.28	-0.52 Units on a scale Interval -0.84 to -0.19	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8 and Week 12

Population: The FAS3 included all participants who received at least 1 dose of randomized treatment in Stage 3.

The LS mean (with 90% CI) of CSM of the TIS (aldolase and creatine kinase) at weeks 4, 8, 12 were presented.

Outcome measures

Outcome measures
Measure	(Stage 1) Placebo n=9 Participants Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	PF-06823859 600 mg IV (Stage 1) n=9 Participants Participants were randomized to receive PF-06823859 600 mg on Day 1, Week 4, and Week 8 in Stage 1.	(Stage 2) Placebo Participants in this group were randomized to receive placebo on Day 1, Week 4, and Week 8. After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 150 mg IV Participants in this group were randomized to receive PF-06823859 150 mg on Day 1, Week 4, and Week 8 After week 12, participants went into a follow up period.	(Stage 2) PF-06823859 600 mg IV Dosing occurred Day 1, Week 4, and Week 8. After week 12, participants went into a follow-up period.	(Amended Stage 2) Placebo Then Switched to PF-06823859 150 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred on Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 150 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16 and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Amended Stage 2) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants then entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) Placebo Then Switched to PF-06823859 600 mg IV at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.	(Stage 3) PF-06823859 600 mg IV Then Switched to Placebo at Week 12 Dosing occurred Day 1, Weeks 4, 8, 12, 16, and 20. At Week 24, participants entered a 4-month follow-up period or rolled over to the long-term extension study.
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Aldolase Week 4	-0.19 Units per litre (U/L) Interval -1.34 to 0.96	-3.09 Units per litre (U/L) Interval -4.25 to -1.92	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Aldolase Week 8	-1.31 Units per litre (U/L) Interval -2.45 to -0.16	-3.57 Units per litre (U/L) Interval -4.74 to -2.4	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Aldolase Week 12	-0.66 Units per litre (U/L) Interval -2.18 to 0.86	-3.20 Units per litre (U/L) Interval -4.76 to -1.64	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Creatine Kinase Week 4	-37.96 Units per litre (U/L) Interval -119.16 to 43.24	-157.48 Units per litre (U/L) Interval -238.68 to -76.28	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Creatine Kinase Week 8	-70.96 Units per litre (U/L) Interval -137.03 to -4.9	-175.93 Units per litre (U/L) Interval -241.99 to -109.86	—	—	—	—	—	—	—	—	—
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3) Creatine Kinase ) Week 12	-39.85 Units per litre (U/L) Interval -125.71 to 46.01	-185.77 Units per litre (U/L) Interval -273.92 to -97.62	—	—	—	—	—	—	—	—	—

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 22 other events

Deaths: 1 deaths

PF-06823859 150 mg IV

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

PF-06823859 600 mg IV

Serious events: 4 serious events

Other events: 18 other events

Deaths: 1 deaths

Total

Serious events: 5 serious events

Other events: 45 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=45 participants at risk Participants who received placebo in any stage.	PF-06823859 150 mg IV n=17 participants at risk Participants who received PF-06823859 150 mg IV in any stage.	PF-06823859 600 mg IV n=47 participants at risk Participants who received PF-06823859 600 mg IV in any stage.	Total n=75 participants at risk This arm included all participants (32, 9, 16 and 18 participants who were randomized and treated in Stage 1, Stage 2, Amended Stage 2, and Stage 3, respectively) in the safety analysis set
Blood and lymphatic system disorders Cytopenia	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Blood and lymphatic system disorders Leukopenia	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	2.1% 1/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Gastrointestinal disorders Colitis microscopic	0.00% 0/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	2.1% 1/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Hepatobiliary disorders Ocular icterus	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Immune system disorders Haemophagocytic lymphohistiocytosis	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Injury, poisoning and procedural complications Humerus fracture	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	2.1% 1/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Investigations Blood bilirubin increased	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Investigations Hepatic enzyme increased	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	2.1% 1/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.
Nervous system disorders Central nervous system lesion	2.2% 1/45 • Up to Week 40 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.	0.00% 0/17 • Up to Week 40 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.	0.00% 0/47 • Up to Week 40 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.	1.3% 1/75 • Up to Week 40 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.

Other adverse events

Additional Information

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Results disclosure agreements

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