A Study In Adults With Moderate To Severe Dermatomyositis

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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