A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item patient-reported outcome (PRO) instrument developed on the basis of the Quantitative Myasthenia Gravis (QMG). The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

MG-C scale is a validated assessment and scale tests 10 items with individual item being weighted differently. The items included ptosis/upward gaze (range: 0 \[\>45 second\] - 3 \[Immediate\]), double vision on lateral gaze (range: 0 \[\>45 second\] - 4 \[Immediate\]), eye closure (range: 0 \[Normal\] - 2 \[severe weakness\]), talking (range: 0 \[Normal\] - 6 \[difficult to understand speech\]), chewing (range: 0 \[Normal\] - 6 \[gastric tube\]), swallowing (range: 0 \[Normal\] - 6 \[gastric tube\]), breathing (range: 0 \[Normal\] - 9 \[ventilator dependence\]), neck flexion (range: 0 \[Normal\] - 4 \[severe weakness\]), shoulder abduction (range: 0 \[Normal\] - 5 \[severe weakness\]) and hip flexion (range: 0 \[Normal\] - 5 \[severe weakness\]), lower scores= lower disease activity. Total MG-C score was obtained by summing responses to each individual item and score ranges from 0 to 50, with lower scores indicating lower disease activity. A positive change indicates worsening and a negative change indicates improvement.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

The QMG is a validated assessment and the scale tested 13 items, including ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. The total QMG score was obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3) and the score ranges from 0 to 39, with lower scores indicating lower disease activity. A positive change in the score indicates worsening and a negative change indicates improvement.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that best described severity of bulbar muscle weakness (items 6-15) symptoms over past 7 days using a 4-point Likert scale (1=none to 4=severe) for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that how frequently they experienced muscle weakness fatigability (items 34-42) over the past 7 days using a 5-point Likert scale (1=none of the time to 5=all of the time) for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose the response option that how frequently they experienced physical fatigue (items 19-33) over the past 7 days using a 5-point Likert scale (1=none of the time to 5=all of the time) for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.

Time frame: Baseline and Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.

A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) up to and including 8 weeks after the last dose.

Time frame: From Baseline until End of Study Visit (up to Week 14)

Population: The Safety Set consisted of all randomized study participants who received at least one dose of IMP and were analyzed according to the actual treatment the participants received. Two participants randomized to RLZ \~7mg/kg, were administered RLZ \~10mg/kg at baseline visit. So, these two participants were included in RLZ \~7 mg/kg group in randomized set, but in RLZ \~10 mg/kg group in safety set.

A TEAE is defined as an AE starting on or after the time of first administration of IMP up to and including 8 weeks after the last dose.

Time frame: From Baseline until End of Study Visit (up to Week 14)

Population: The Safety Set consisted of all randomized study participants who received at least one dose of IMP and were analyzed according to the actual treatment the participants received. Two participants randomized to RLZ \~7mg/kg, were administered RLZ \~10mg/kg at baseline visit. So, these two participants were included in RLZ \~7 mg/kg group in randomized set, but in RLZ \~10 mg/kg group in safety set.

The MG-ADL is an 8-item PRO instrument developed on the basis of the QMG. The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement. Study participants were classified as responders at Day 43 if the value was at least a 2-point improvement (decrease) from Baseline at Day 43.

Time frame: Day 43

Population: The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.