Study of M5049 in DM and PM Participants (NEPTUNIA)

The ACR/EULAR TIS was derived from evaluation of results from 6 Core Set Measures(CSMs) of myositis disease activity in participants with Dermatomyositis and Polymyositis.TIS was determined by summing scores for each CSM,based on improvement in absolute percent change which is calculated by subtracting the baseline value from the final value,dividing difference by the range, and then multiplying the result by100 and relative weight of each core set measure. The TIS scale ranges from 0 to 100 with thresholds for minimal [more than or equal to(>= 20)],moderate(>= 40) and major(>= 60)improvement in combined 6 CSM.The CSMs include,physician global activity visual analogue scale(VAS) score(0-10), patient global activity VAS score(0-10), manual muscle testing-8 score(0-150), health assessment questionnaire-disability index(0-3) along with checks for most abnormal muscle-associated enzymes and extra muscular activity assessment derived using myositis disease activity assessment tool(0-10).

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.

Laboratory parameters included hematology, biochemistry, urinalysis and reflex testing for HBV DNA. Number of participants with clinically meaningful changes from baseline in laboratory parameters were reported. Clinical meaningfulness was assessed by the investigator.

Vital signs included body temperature, systolic and diastolic blood pressure, respiration rate, pulse rate, weight, height and body mass index. Number of participants with clinically meaningful changes from baseline in vital signs were reported. Clinical meaningfulness was assessed by the investigator.

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Number of participants with clinically meaningful changes from baseline in ECG parameters were reported. Clinical meaningfulness was assessed by the investigator.

The ACR/EULAR TIS was derived from evaluation of results from 6 Core Set Measures(CSMs) of myositis disease activity in participants with Dermatomyositis and Polymyositis.TIS was determined by summing scores for each CSM,based on improvement in absolute percent change which is calculated by subtracting the baseline value from the final value,dividing difference by the range, and then multiplying the result by100 and relative weight of each core set measure. The TIS scale ranges from 0 to 100 with thresholds for minimal [more than or equal to(>= 20)],moderate(>=40) and major(>=60)improvement in combined 6 CSM.The CSMs include,physician global activity visual analogue scale(VAS) score(0-10), patient global activity VAS score(0-10), manual muscle testing-8 score(0-150), health assessment questionnaire-disability index(0-3) along with checks for most abnormal muscle-associated enzymes and extra muscular activity assessment derived using myositis disease activity assessment tool(0-10).

The ACR/EULAR TIS was derived from evaluation of results from 6 Core Set Measures(CSMs) of myositis disease activity in participants with Dermatomyositis and Polymyositis.TIS was determined by summing scores for each CSM,based on improvement in absolute percent change which is calculated by subtracting the baseline value from the final value,dividing difference by the range, and then multiplying the result by100 and relative weight of each core set measure. The TIS scale ranges from 0 to 100 with thresholds for minimal [more than or equal to(>= 20)],moderate(>=40) and major(>=60)improvement in combined 6 CSM.The CSMs include,physician global activity visual analogue scale(VAS) score(0-10), patient global activity VAS score(0-10), manual muscle testing-8 score(0-150), health assessment questionnaire-disability index(0-3) along with checks for most abnormal muscle-associated enzymes and extra muscular activity assessment derived using myositis disease activity assessment tool(0-10).

The Physician's Global Assessment of Disease Activity was an assessment of overall global disease activity by the physician that was taken from Myositis Disease Activity Assessment Tool (MDAAT). Physician rated participant's disease activity on a 0-10 centimeter (cm) visual analog scale (VAS). Extra-muscular activity ranged between 0 and 10, where, 0 cm = absent and 10 cm = maximum disease activity.

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

MDAAT was a combined tool capturing physician's assessment of disease activity of various organ systems- constitutional, cutaneous, pulmonary, gastrointestinal, joints and cardiovascular, muscular using: Myositis Intention to Treat Activity Index (MITAX), a scale from 0("Not present in the last 4 weeks") to 4("New - in the last 4 weeks [compared to the previous 4 weeks]") and Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT), a 10 cm VAS assessing disease activity in the last 4 weeks of various organ systems from 0 cm("No evidence of disease activity") to 10 cm("Extremely active or severe disease activity"), disease activity being defined as potentially reversible pathology or physiology resulting from the myositis. Left end of line = no evidence of disease activity, midpoint of line = moderate disease activity, and right end of line = extreme or maximum disease activity. An assessment of extramuscular activity assessment was taken from MDAAT using a 10cm VAS scale.

MMT-8 was an International Myositis Assessment and Clinical Studies (IMACS) Core Set Measure used in the calculation of the IMACS Definition of Improvement (DOI) and ACR/EULAR TIS. It is a set of 8 designated muscles tested unilaterally (generally on right side) -which include 1 axial, 5 proximal (2 upper extremity, 3 lower extremity), and 2 distal muscles (1 upper, 1 lower extremity). Total score for unilateral testing ranges from 0 to 80, and bilateral testing ranges from 0 to 150 with normal strength represented by a higher score at or near the top of the scale. The total score for bilateral testing (item "MMT8 score (0 - 150)" from the MANUAL MUSCLE TESTING-8 (mmt8) form) is used in the derivation of the Total Improvement Score.

HAQ-DI was an IMACS Core Set Measure used in the calculation of the IMACS DOI and ACR/EULAR TIS. It is a generic rather than a disease-specific instrument comprised of 8 sections (dressing, arising, eating, walking, hygiene, reach, grip, and activities), with 2 to 3 questions per section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8. Overall score ranges from 0-3.

For each participant, the most abnormal muscle-associated enzyme was defined as the baseline muscle-associated enzyme with the highest ratio of the observed value to the upper limit of the normal range (ULN) among creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and aldolase. The relative abnormality could be expressed as a percentage of ULN, calculated as (enzyme value divided by ULN) multiplied by 100.

A participant was defined as an International Myositis Assessment and Clinical Studies (IMACS) Responder if 3 of any 6 IMACS Core Set Measures (CSMs) have been improved by more than equal to (>= 20) percent (%), with no more than 2 IMACS CSMs worse by >= 25%. The CSMs include, physician global activity visual analogue scale(VAS) score(0-10), patient global activity VAS score(0-10), manual muscle testing-8 score(0-150), health assessment questionnaire-disability index (0-3) along with checks for muscle-associated enzymes and extra muscular activity assessment derived using myositis disease activity assessment tool(0-10).

CDASI is a clinician-scored single page instrument that separately measures activity and damage in the skin of DM participants. CDASI has 3 activity measures (CDASI-A: erythema, scale, and erosion/ulceration) and 2 damage measures (CDASI-D: poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands, periungual changes and alopecia are evaluated separately both for activity and damage. Activity and Damage Subscale scores range from 0 to 100 and 0 to 32, respectively, where higher scores indicate greater disease severity.

The IGA skin activity is a five-point score that defines the level of disease severity based on overall lesion characteristics where 0 is "clear" and "4" is severe.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.

Laboratory parameters included hematology, biochemistry, urinalysis and reflex testing for HBV DNA. Number of participants with clinically meaningful changes from baseline in laboratory parameters were reported. Clinical meaningfulness was assessed by the investigator.

Vital signs included body temperature, systolic and diastolic blood pressure, respiration rate, pulse rate, weight, height and body mass index. Number of participants with clinically meaningful changes from baseline in vital signs were reported. Clinical meaningfulness was assessed by the investigator.

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Number of participants with clinically meaningful changes from baseline in ECG parameters were reported. Clinical meaningfulness was assessed by the investigator.