Subcutaneous Treatment In Randomized Subjects To Evaluate Safety And Efficacy In Generalized Lupus Erythematosus

SRI components include:SLEDAI-2K ,BILAG 2004, PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG:assesses disease extent, severity (range: A [severe] to E [no disease]). PhGA: assesses worsening in participant's general health status(range: 0[none] to 3[severe]).

SRI components include: modified SLEDAI-2K (SLEDAI-2K without standard parameters "Low complement" and "Leukopenia"), BILAG 2004, PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. Modified SLEDAI-2K: assesses improvement in disease activity (range: 0 to 102; higher score = higher severity). BILAG: assesses disease extent, severity (range: A [severe] to E [no disease]). PhGA: assesses worsening in participant's general health status (range: 0[none] to 3[severe]).

BICLA include: BILAG-2004, SLEDAI-2K, PhGA of disease activity. Participants classified as responder if they did not meet the definition of treatment failure and met all the following criteria: BILAG-2004 improvement (all A scores at baseline improved to B/C/D and all B scores improved to C or D); no worsening in disease activity (no new BILAG-2004 A scores or =<1 new B score); no worsening of total SLEDAI-2K score; no significant deterioration (<10 percent [%] worsening) in analogue PhGA. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. BILAG:assesses disease extent, severity (range: A[severe] to E[no disease]). SLEDAI-2K:assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). PhGA: assesses worsening in participant's general health status(range: 0[none] to 3[severe]).

SRI components include: SLEDAI-2K, BILAG 2004 and PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening(<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K: assesses improvement in disease activity(range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity (range: A[severe] to E [no disease]). PhGA: assesses worsening in participant's general health status (range: 0[none] to 3[severe]). Model percent estimates reported only for 'Reduction in SLEDAI Score','No Worsening in PhGA' categories; for remaining categories, raw percentages reported

Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. Laboratory values included Alanine Aminotransferase (ALT) [>5.0 - 10.0*Upper limit of normal range (ULN)], Albumin [<26-20 gram per liter (g/L)/ <20 g/L], Amylase [>2.0 - 5.0*ULN], Aspartate Aminotransferase (AST) [>5.0 - 10.0*ULN], Creatine Kinase (CK) [>5.0 - 10.0* ULN/ >10.0*ULN], Glucose (Hyperglycemia) [>13.9 - 27.8 millimoles/liter (mmol/L)], Hemoglobin (HGB) [<80 - 65 g/L/ <65 g/L], Lipase [>2.0 - 5.0*ULN], Lymphocytes (Lymph.)(Absolute [Abs]) [<0.5 - 0.2*10^3/microliter (UL)/ <0.2*10^3/UL], Platelets [<50-25*10^3/UL/ <25*10^3/UL], potassium (low) [<3.0 - 2.5 mmol/L], Sodium (low) [<130 - 120 mmol/L], Total Neutrophils (TN) (Abs) [<1.0 - 0.5*10^3/UL/ <0.5*10^3/UL], Triglycerides [>5.7 - 11.4 mmol/L], White Blood Cell Count (WBC) [<2.0 - 1.0*10^3/UL/ <1.0*10^3/UL].

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants who discontinued due to adverse events were reported.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of participants with treatment-emergent AEs or SAEs (excluding infectious AEs or SAEs and injection site reactions) were reported. AEs include both SAEs and non-SAEs.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of participants with treatment-emergent infectious AEs or SAEs were reported. AEs include both SAEs and non-SAEs.

Criteria for potentially clinically important (PCI) findings in ECG were defined as: heart rate <=40 beats per minute (bpm) or >=120 bpm; PR interval >=220 millisecond (msec); QT interval >=480 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) >=500msec; no sinus rhythm.

Criteria for PCI findings in vital signs were defined as: sitting systolic blood pressure (Increase from baseline >=20 millimeter of mercury (mm Hg) and >=160 mm Hg or a decrease from baseline >=20 mm Hg and <=90 mm Hg) and sitting diastolic blood pressure (increase from baseline >=15 mm Hg and >=90 mm Hg or decrease from baseline >=15 mm Hg and <=60 mm Hg), pulse rate (increase from baseline >=15 beats/min and >=120 beats/min or decrease from baseline >=15 beats/min and <=50 beats /min), body temperature (increase of >=2 degree Fahrenheit (F) and temperature >=101 degree F) and weight (change of >=7% in body weight)

Human serum samples were analyzed for the presence or absence of anti-PF-04236921 antibodies. A positive ADA sample was further tested for neutralizing antibodies using a validated assay.

Serum PF-04236921 concentrations over time were summarized.

Participants were given supplemental corticosteroids at baseline to control disease activity, if necessary. The steroid taper was based on participant's symptoms. Participants recorded their steroid usage on a diary card. Least Observation Carried Forward (LOCF) method was used to impute missing data.

Serologic activity was to be assessed in the subgroup of participants who had positive serologic activity at baseline.

Participants assessed their disease activity using a 100 millimeter (mm) VAS. Participants answered the following question "Considering all the ways your disease affects you, how are you feeling today?" Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad).

Participants assessed their disease activity using a 100 mm VAS. Participants answered the following question "Considering all the ways your disease affects you, how are you feeling today?" Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad).

EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point VAS (0= worst imaginable health state, 100= best imaginable health state).

SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and mental component score MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Vitality sub-score is a component of SF-36 Health Survey Questionnaire and assesses energy and fatigue. The vitality score ranged from 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.

The SF-6D focuses on seven of the eight health domains covered by the SF-36 Health Survey: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. The SF-6D is an attempt to derive a single index from the SF-36 Health Survey for use in economic evaluation studies. As such, it represents a summary score based on a subset of the SF-36 data. Consequently, in lieu of the SF-6D, PCS and MCS SF-36 results are being provided. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). LOCF method was used to impute missing values.