Trial Outcomes & Findings for A Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness (NCT NCT02965573)

Last Updated: 2024-08-28

Results Overview

TEAEs were defined as AEs that first occurred or worsened in severity after the first administration of the treatment. A treatment emergent SAE was any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability or incapacity; was a congenital abnormality or birth defect; or other medically significant events. All TEAEs observed were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 with descriptions of severity for each AE based on the following general guideline: Grade 1= mild; Grade 2 = moderate; Grade 3 = severe or medically significant but not immediately life-threatening; Grade 4 = life-threatening consequences; Grade 5 = death related to AE.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Day 1 to Day 78

Results posted on

2024-08-28

Participant Flow

From 30 December 2016, 15 study centers in 8 countries (Belgium, Canada, Italy, the Netherlands, Poland, Spain, Sweden, and United States) consented at least 1 patient with myasthenia gravis (MG) who had generalized muscle weakness. The last patient last visit was 20 October 2017.

The study included a maximum screening period of 15 days to evaluate patients' eligibility. Eligible patients were randomized in a 1:1 ratio to receive either ARGX-113 at 10 milligram/ kilogram (mg/kg) body weight or placebo, in addition to Standard of Care (SoC). The study involved a 3-week treatment period and an 8-week follow-up period.

Participant milestones

Participant milestones
Measure	ARGX-113 Patients received ARGX-113 at a dose of 10 mg/kg in 4 intravenous (IV) infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Study STARTED	12	12
Overall Study COMPLETED	11	12
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ARGX-113 Patients received ARGX-113 at a dose of 10 mg/kg in 4 intravenous (IV) infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

A Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	55.3 years STANDARD_DEVIATION 13.60 • n=5 Participants	43.5 years STANDARD_DEVIATION 19.28 • n=7 Participants	49.4 years STANDARD_DEVIATION 17.39 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Weight	74.08 kg STANDARD_DEVIATION 15.477 • n=5 Participants	75.21 kg STANDARD_DEVIATION 14.343 • n=7 Participants	74.64 kg STANDARD_DEVIATION 14.604 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 78

Population: The safety analysis set included all patients in the randomized population who received at least 1 dose or part of a dose. The safety analysis was based on the actual treatment received.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) At least 1 TEAE	10 Participants	10 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) At least 1 treatment-related TEAE	8 Participants	3 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) At least 1 treatment emergent SAE	0 Participants	0 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) Withdrawn from treatment with at least 1 TEAE	0 Participants	0 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) Discontinued study due to at least 1 TEAE	0 Participants	0 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) NCI-CTCAE severity Grade ≥3	0 Participants	0 Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) Number of Deaths	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Population: The safety analysis set included all patients in the randomized population who received at least 1 dose or part of a dose. The safety analysis was based on the actual treatment received. Only patients with data available for analysis are presented.

The patients' diastolic and systolic blood pressure were measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

Outcome measures

PRIMARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

The patients' heart rate was measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in Vital Signs: Heart Rate Day 8	-2.7 beats/minute Standard Deviation 11.80	1.8 beats/minute Standard Deviation 11.66
Mean Change From Baseline in Vital Signs: Heart Rate Day 15	-4.1 beats/minute Standard Deviation 9.05	2.5 beats/minute Standard Deviation 12.40
Mean Change From Baseline in Vital Signs: Heart Rate Day 22	-0.8 beats/minute Standard Deviation 10.70	-1.1 beats/minute Standard Deviation 12.15
Mean Change From Baseline in Vital Signs: Heart Rate Day 29	-2.4 beats/minute Standard Deviation 13.49	0.1 beats/minute Standard Deviation 9.75
Mean Change From Baseline in Vital Signs: Heart Rate Day 36	1.1 beats/minute Standard Deviation 14.08	3.1 beats/minute Standard Deviation 11.87
Mean Change From Baseline in Vital Signs: Heart Rate Day 43	0.2 beats/minute Standard Deviation 10.79	3.1 beats/minute Standard Deviation 15.49
Mean Change From Baseline in Vital Signs: Heart Rate Day 50	0.5 beats/minute Standard Deviation 19.82	2.1 beats/minute Standard Deviation 12.98
Mean Change From Baseline in Vital Signs: Heart Rate Day 64	-4.0 beats/minute Standard Deviation 19.22	0.6 beats/minute Standard Deviation 8.71
Mean Change From Baseline in Vital Signs: Heart Rate Day 78	-3.1 beats/minute Standard Deviation 10.78	-2.0 beats/minute Standard Deviation 15.12

PRIMARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

The patients' temperature was measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in Vital Signs: Temperature Day 8	0.18 degrees Centigrade Standard Deviation 0.493	0.15 degrees Centigrade Standard Deviation 0.511
Mean Change From Baseline in Vital Signs: Temperature Day 15	0.09 degrees Centigrade Standard Deviation 0.535	0.16 degrees Centigrade Standard Deviation 0.382
Mean Change From Baseline in Vital Signs: Temperature Day 22	0.05 degrees Centigrade Standard Deviation 0.613	0.27 degrees Centigrade Standard Deviation 0.429
Mean Change From Baseline in Vital Signs: Temperature Day 29	-0.03 degrees Centigrade Standard Deviation 0.459	0.11 degrees Centigrade Standard Deviation 0.291
Mean Change From Baseline in Vital Signs: Temperature Day 36	-0.13 degrees Centigrade Standard Deviation 0.620	0.09 degrees Centigrade Standard Deviation 0.334
Mean Change From Baseline in Vital Signs: Temperature Day 43	-0.04 degrees Centigrade Standard Deviation 0.563	0.08 degrees Centigrade Standard Deviation 0.299
Mean Change From Baseline in Vital Signs: Temperature Day 50	-0.03 degrees Centigrade Standard Deviation 0.341	0.10 degrees Centigrade Standard Deviation 0.422
Mean Change From Baseline in Vital Signs: Temperature Day 64	0.21 degrees Centigrade Standard Deviation 0.593	0.17 degrees Centigrade Standard Deviation 0.306
Mean Change From Baseline in Vital Signs: Temperature Day 78	0.11 degrees Centigrade Standard Deviation 0.552	0.18 degrees Centigrade Standard Deviation 0.282

PRIMARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

The patients' weight as measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in Vital Signs: Weight Day 8	0.18 kg Standard Deviation 0.443	-0.02 kg Standard Deviation 1.359
Mean Change From Baseline in Vital Signs: Weight Day 15	0.60 kg Standard Deviation 0.768	0.31 kg Standard Deviation 1.528
Mean Change From Baseline in Vital Signs: Weight Day 22	0.54 kg Standard Deviation 0.672	0.01 kg Standard Deviation 1.672
Mean Change From Baseline in Vital Signs: Weight Day 29	0.41 kg Standard Deviation 0.729	-0.04 kg Standard Deviation 1.826
Mean Change From Baseline in Vital Signs: Weight Day 36	0.76 kg Standard Deviation 0.840	-0.02 kg Standard Deviation 1.770
Mean Change From Baseline in Vital Signs: Weight Day 43	0.91 kg Standard Deviation 2.093	0.31 kg Standard Deviation 2.593
Mean Change From Baseline in Vital Signs: Weight Day 50	0.48 kg Standard Deviation 1.156	0.44 kg Standard Deviation 1.996
Mean Change From Baseline in Vital Signs: Weight Day 64	0.26 kg Standard Deviation 1.052	-0.27 kg Standard Deviation 2.703
Mean Change From Baseline in Vital Signs: Weight Day 78	0.23 kg Standard Deviation 1.238	-0.60 kg Standard Deviation 3.122

PRIMARY outcome

Timeframe: Day 1 to Day 78

Population: The safety analysis set included all patients in the randomized population who received at least 1 dose or part of a dose. The safety analysis was based on the actual treatment received.

ECG parameters of heart rate, PR, QT, and QRS interval were read locally and performed pre-dose on dosing days 1,8,15 and 22 and on the last follow up visit on Day 78. Any patients recording abnormal clinically relevant findings during the study are presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 78

Population: The safety analysis set included all patients in the randomized population who received at least 1 dose or part of a dose. The safety analysis was based on the actual treatment received.

Sampling for clinical laboratory tests including hematology, clinical chemistry, and urinalysiswas performed pre-dose on dosing Days 1, 8, 15 and 22 and throughout the follow up period. Patients fasted for at least 8 hours prior to this sampling. Abnormal laboratory values, or test results were not reported as TEAEs unless they were associated with clinical signs and symptoms that were considered clinically relevant, required therapy or led to treatment discontinuation. Patients reporting TEAEs in any of the laboratory parameters during the study are presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs B-lymphocyte count decreased	2 Participants	0 Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs T-lymphocyte count decreased	1 Participants	0 Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs Lymphocyte count decreased	2 Participants	0 Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs Monocyte count decreased	2 Participants	0 Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs Neutrophil count inceased	2 Participants	0 Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs Blood thyroid stimulating hormone increased	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Population: The full analysis set (FAS) included all randomized patients with at least 1 of the MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite (MGC), and 15-item Quality of Life scale for Myasthenia Gravis revised version (MGQoL15r) scales available for 1 of the postbaseline assessments up to Day 78 along with the corresponding baseline value. Only patients with data available for analysis are presented.

The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. It evaluates the capacity to perform different activities of daily living such as talking, chewing, swallowing, breathing, brushing the teeth/combing the hair, or arising from the chair and it also assesses double vision and eyelid droop. The 8 items are rated from 0 to 3 and the total score could point from 0 to 24; with higher scores indicating more impairment. The mean change in MG-ADL score from baseline is presented for each timepoint with a clinically meaningful improvement defined as a drop of at least 2 points as compared with baseline.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 8	-1.9 score on a scale Standard Deviation 2.75	-0.7 score on a scale Standard Deviation 1.56
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 15	-2.8 score on a scale Standard Deviation 2.70	-2.2 score on a scale Standard Deviation 2.08
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 22	-3.5 score on a scale Standard Deviation 2.84	-2.5 score on a scale Standard Deviation 2.50
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 29	-4.1 score on a scale Standard Deviation 2.64	-2.3 score on a scale Standard Deviation 2.72
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 36	-4.2 score on a scale Standard Deviation 3.30	-2.1 score on a scale Standard Deviation 2.43
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 43	-3.8 score on a scale Standard Deviation 2.72	-2.4 score on a scale Standard Deviation 2.69
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 50	-4.4 score on a scale Standard Deviation 3.53	-2.9 score on a scale Standard Deviation 2.96
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 64	-3.4 score on a scale Standard Deviation 3.27	-1.8 score on a scale Standard Deviation 3.55
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Day 78	-3.5 score on a scale Standard Deviation 3.50	-1.8 score on a scale Standard Deviation 4.22

SECONDARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Population: The FAS includes all randomized patients with at least 1 of the MG-ADL, QMG, MGC, and MGQoL15r scales available for 1 of the postbaseline assessments up to Day 78 along with the corresponding baseline value. Only patients with data available for analysis are presented.

The QMG quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG consists of 13 items that includes ocular, bulbar, and limb function. Out of the 13 items, 6 are timed tests of endurance measured in seconds. Each item has a possible score from 0-3. The score range is 0-39, where higher scores indicate more severe impairments. The mean change in QMG score from baseline is presented with a clinically meaningful improvement defined as a drop of at least 3 points as compared with baseline.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in QMG Score Day 8	-2.8 score on a scale Standard Deviation 3.13	0.0 score on a scale Standard Deviation 2.22
Mean Change From Baseline in QMG Score Day 15	-4.0 score on a scale Standard Deviation 4.29	-1.8 score on a scale Standard Deviation 3.08
Mean Change From Baseline in QMG Score Day 22	-4.0 score on a scale Standard Deviation 4.55	-1.8 score on a scale Standard Deviation 3.91
Mean Change From Baseline in QMG Score Day 29	-4.9 score on a scale Standard Deviation 4.94	-1.4 score on a scale Standard Deviation 3.72
Mean Change From Baseline in QMG Score Day 36	-5.7 score on a scale Standard Deviation 5.97	-1.9 score on a scale Standard Deviation 3.37
Mean Change From Baseline in QMG Score Day 43	-4.6 score on a scale Standard Deviation 5.73	-2.1 score on a scale Standard Deviation 4.55
Mean Change From Baseline in QMG Score Day 50	-5.5 score on a scale Standard Deviation 5.84	-2.1 score on a scale Standard Deviation 3.95
Mean Change From Baseline in QMG Score Day 64	-4.5 score on a scale Standard Deviation 6.42	-1.8 score on a scale Standard Deviation 4.59
Mean Change From Baseline in QMG Score Day 78	-4.8 score on a scale Standard Deviation 7.67	-2.1 score on a scale Standard Deviation 5.07

SECONDARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

The MGC has 10 items combining physician examination and patient-reported outcomes. The 2 ocular items are derived from QMG. It has 3 items on muscle strength (deltoids, hip flexors, and neck flexors or extensors) and 4 items on bulbar function (swallowing, chewing, breathing, and speech functions), based on the clinical history. Each item is scored on an ordinal scale with 4 possible categories, but the items are weighted, whereby bulbar impairments weigh more than ocular ones. The impairments that were examined by the Investigator included ptosis or upward gaze, double vision, eye closure, neck flexion, shoulder abduction, and hip flexion. The patient-reported outcomes under MGC are talking, chewing, swallowing, and breathing. The maximum possible score is 50 (range from 0-50), with higher scores reflecting more severe impairments. The mean change in MGC score from baseline is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in MGC Score Day 8	-4.3 score on a scale Standard Deviation 5.87	-1.3 score on a scale Standard Deviation 2.77
Mean Change From Baseline in MGC Score Day 15	-5.8 score on a scale Standard Deviation 6.45	-4.4 score on a scale Standard Deviation 4.56
Mean Change From Baseline in MGC Score Day 22	-7.8 score on a scale Standard Deviation 6.92	-4.0 score on a scale Standard Deviation 3.86
Mean Change From Baseline in MGC Score Day 29	-8.7 score on a scale Standard Deviation 7.36	-4.1 score on a scale Standard Deviation 5.22
Mean Change From Baseline in MGC Score Day 36	-9.0 score on a scale Standard Deviation 8.73	-4.1 score on a scale Standard Deviation 5.58
Mean Change From Baseline in MGC Score Day 43	-8.6 score on a scale Standard Deviation 8.54	-3.5 score on a scale Standard Deviation 5.97
Mean Change From Baseline in MGC Score Day 50	-9.4 score on a scale Standard Deviation 7.92	-4.2 score on a scale Standard Deviation 5.51
Mean Change From Baseline in MGC Score Day 64	-7.2 score on a scale Standard Deviation 8.65	-3.8 score on a scale Standard Deviation 6.84
Mean Change From Baseline in MGC Score Day 78	-7.1 score on a scale Standard Deviation 9.71	-3.8 score on a scale Standard Deviation 6.83

SECONDARY outcome

Timeframe: Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

The MGQoL15r is a quality of life scale or survey of patient's responses that addresses MG-specific psychological well-being and social functioning. It is a brief questionnaire that is completed by the patient and uses 3 response options to help inform the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Each item is scored from 0 to 2 according to its frequency, with a maximum score of 30 (range 0-30) and higher scores reflecting more severe impairment. The mean change in MGQoL15r score from baseline is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in MGQoL15r Score Day 8	-2.0 score on a scale Standard Deviation 5.77	-0.8 score on a scale Standard Deviation 1.86
Mean Change From Baseline in MGQoL15r Score Day 15	-3.7 score on a scale Standard Deviation 4.42	-1.0 score on a scale Standard Deviation 2.76
Mean Change From Baseline in MGQoL15r Score Day 22	-4.3 score on a scale Standard Deviation 4.77	-1.5 score on a scale Standard Deviation 3.17
Mean Change From Baseline in MGQoL15r Score Day 29	-4.7 score on a scale Standard Deviation 5.44	-1.5 score on a scale Standard Deviation 2.91
Mean Change From Baseline in MGQoL15r Score Day 36	-6.0 score on a scale Standard Deviation 5.78	-2.1 score on a scale Standard Deviation 3.58
Mean Change From Baseline in MGQoL15r Score Day 43	-5.3 score on a scale Standard Deviation 5.59	-1.4 score on a scale Standard Deviation 3.70
Mean Change From Baseline in MGQoL15r Score Day 50	-4.4 score on a scale Standard Deviation 4.13	-1.8 score on a scale Standard Deviation 3.71
Mean Change From Baseline in MGQoL15r Score Day 64	-3.7 score on a scale Standard Deviation 5.10	-1.3 score on a scale Standard Deviation 3.68
Mean Change From Baseline in MGQoL15r Score Day 78	-2.7 score on a scale Standard Deviation 5.44	-1.5 score on a scale Standard Deviation 3.61

SECONDARY outcome

Timeframe: Day 1 to Day 78

The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. It evaluates the capacity to perform different activities of daily living such as talking, chewing, swallowing, breathing, brushing the teeth/combing the hair, or arising from the chair and it also assesses double vision and eyelid droop. The 8 items are rated from 0 to 3 and the total score could point from 0 to 24; with higher scores indicating more impairment. The mean maximum reduction from baseline across all visit days for MG-ADL score is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Maximum Reduction From Baseline in MG-ADL Score	-5.1 score on a scale Standard Deviation 3.32	-3.7 score on a scale Standard Deviation 2.93

SECONDARY outcome

Timeframe: Day 1 to Day 78

The QMG quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG consists of 13 items that included ocular, bulbar, and limb function. Out of the 13 items, 6 are timed tests of endurance measured in seconds. Each item has a possible score from 0-3. The total possible score is 39 (range 0-39), where higher scores indicates more severe impairments. The mean maximum reduction from baseline across all visit days for QMG score is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Maximum Reduction From Baseline in QMG Score	-7.3 score on a scale Standard Deviation 6.08	-4.3 score on a scale Standard Deviation 4.16

SECONDARY outcome

Timeframe: Day 1 to Day 78

The MGC has 10 items combining physician examination and patient-reported outcomes. The 2 ocular items are derived from QMG. It has 3 items on muscle strength (deltoids, hip flexors, and neck flexors or extensors) and 4 items on bulbar function (swallowing, chewing, breathing, and speech functions), based on the clinical history. Each item is scored on an ordinal scale with 4 possible categories, but the items are weighted, whereby bulbar impairments weigh more than ocular ones. The impairments that were examined by the Investigator included ptosis or upward gaze, double vision, eye closure, neck flexion, shoulder abduction, and hip flexion. The patient-reported outcomes under MGC are talking, chewing, swallowing, and breathing. The maximum possible score is 50 (range 0-50), with higher scores reflecting more severe impairments. The mean maximum reduction from baseline across all visit days for MCG score is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Maximum Reduction From Baseline in MGC Score	-11.5 score on a scale Standard Deviation 7.61	-7.7 score on a scale Standard Deviation 4.40

SECONDARY outcome

Timeframe: Day 1 to Day 78

The MGQoL15r is a quality of life scale or survey of patient's responses that addresses MG-specific psychological well-being and social functioning. It is a brief questionnaire that was completed by the patient and uses 3 response options to help inform the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Each item is scored from 0 to 2 according to its frequency, with a maximum score of 30 (range 0-30) and higher scores reflecting more severe impairment. The mean maximum reduction from baseline across all visit days for MGQoL15r score is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Maximum Reduction From Baseline in MGQoL15r Score	-7.2 score on a scale Standard Deviation 5.42	-3.0 score on a scale Standard Deviation 3.16

SECONDARY outcome

Timeframe: Days 1, 8, 15 and 22

Population: The PK analysis set included all patients in the randomized population who had at least 1 plasma concentration data value available for ARGX-113 without major protocol deviations thought to impact PK. Patients who did not receive ARGX-113 were not included in the PK analysis set. Only patients with data available for analysis are presented.

The appropriate PK parameters were calculated after single (Day 1) and multiple administrations (Days 8,15 and 22) of ARGX-113. The mean maximum observed plasma concentration (Cmax) and plasma concentration observed pre-dose (Ctrough) is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Ctrough - Day 15	10045.5 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 56.7	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Ctrough - Day 22	10944.6 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 71.1	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Cmax - Day 1	179063.7 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 31.9	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Cmax - Day 8	173960.4 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 19.5	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Cmax - Day 15	153257.2 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 22.1	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Cmax - Day 22	162655.6 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 26.1	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Ctrough - Day 1	7266.2 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 43.5	—
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 Ctrough - Day 8	9894.8 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 54.7	—

SECONDARY outcome

Timeframe: Days 1, 8 15 and 22.

The appropriate PK parameters were calculated after single (Day 1) and multiple administrations (Days 8, 15 and 22) of ARGX-113. The median tmax is presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 Day 1	2.44 hours Interval 2.08 to 2.58	—
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 Day 8	2.50 hours Interval 2.08 to 2.5	—
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 Day 15	2.50 hours Interval 2.07 to 2.5	—
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 Day 22	2.46 hours Interval 2.08 to 2.67	—

SECONDARY outcome

Timeframe: Day 22

The t1/2 lambda z was calculated at Day 22.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113	116.08 hours Geometric Coefficient of Variation 15.8	—

SECONDARY outcome

Timeframe: Days 1 and 22.

Population: The PK analysis set included all patients in the randomized population who had at least 1 plasma concentration data value available for ARGX-113 without major protocol deviations thought to impact PK. Patients who did not receive ARGX-113 were not included in the PK analysis set. Only patinents with data available for analysis are presented.

The Rac was calculated as Day 22 Cmax/Day 1 Cmax.

Outcome measures

Outcome measures
Measure	ARGX-113 n=11 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
PK Parameters - Accumulation Ratio (Rac) of ARGX-113	0.9360 ratio Geometric Coefficient of Variation 25.7	—

SECONDARY outcome

Timeframe: Baseline, Days 22 and 78

Population: The PD analysis set included all patients in the randomized population who had at least 1 non-missing post-dose PD measurement available without major protocol deviations thought to impact PD. Only patients with data available for analysis are presented.

The pharmacodynamic (PD) biomarkers that were measured included the following IgGs: Total IgG and IgG isotypes; IgG1, IgG2, IgG3, IgG4. PD samples were collected pre-dose on dosing days and the mean percent change from baseline at the end of treatment (Day 22) and at the last follow up visit (Day 78) are presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Percent Change From Baseline in Immunoglobulins (IgGs) Total IgG - Day 22	-70.0 percentage change Standard Deviation 10.96	-2.8 percentage change Standard Deviation 15.34
Mean Percent Change From Baseline in Immunoglobulins (IgGs) Total IgG - Day 78	-20.4 percentage change Standard Deviation 24.96	6.4 percentage change Standard Deviation 27.49
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG1 - Day 22	-65.5 percentage change Standard Deviation 8.56	-2.1 percentage change Standard Deviation 9.29
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG1 - Day 78	-16.0 percentage change Standard Deviation 18.17	-1.1 percentage change Standard Deviation 19.01
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG2 - Day 22	-61.0 percentage change Standard Deviation 6.73	-4.4 percentage change Standard Deviation 6.99
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG2 - Day 78	-34.9 percentage change Standard Deviation 16.02	-5.3 percentage change Standard Deviation 17.63
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG3 - Day 22	-65.25 percentage change Standard Deviation 10.045	0.57 percentage change Standard Deviation 9.566
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG3 - Day 78	-5.19 percentage change Standard Deviation 18.422	2.52 percentage change Standard Deviation 15.341
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG4 - Day 22	-49.48 percentage change Standard Deviation 10.278	0.79 percentage change Standard Deviation 6.592
Mean Percent Change From Baseline in Immunoglobulins (IgGs) IgG4 - Day 78	4.16 percentage change Standard Deviation 25.513	1.57 percentage change Standard Deviation 16.730

SECONDARY outcome

Timeframe: Baseline, Days 22 and 78

Population: The PD analysis set includes all patients in the randomized population who had at least 1 non-missing post-dose PD measurement available without major protocol deviations thought to impact PD. Only patients with data available for analysis are presented.

Analysis of the PD biomarkers included anti-AChR binding antibodies. PD samples were collected pre-dose on dosing days and the mean percent change from baseline at the end of treatment (Day 22) and at the last follow up visit (Day 78) are presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies Day 22	-52.2686 percentage change Standard Deviation 26.32992	-0.3236 percentage change Standard Deviation 8.50886
Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies Day 78	-1.3361 percentage change Standard Deviation 34.33867	-7.8881 percentage change Standard Deviation 33.43325

SECONDARY outcome

Timeframe: Baseline up to Day 78

Blood samples to assess ADA were collected pre-dose on dosing days and throughout the follow up period. The overall number of patients with pre-dose and post-dose ADA titers are presented.

Outcome measures

Outcome measures
Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Number of Patients With an Anti-drug Antibodies (ADA) Response Patients with pre-dose ADA titers	4 participants	2 participants
Number of Patients With an Anti-drug Antibodies (ADA) Response Patients with post-dose ADA titers	4 participants	3 participants

Adverse Events

ARGX-113

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Regulatory Manager

argenx BVBA

Phone: +32 93103400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ARGX-113 n=12 Participants Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Placebo n=12 Participants Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 78	2.5 millimeters mercury Standard Deviation 10.82	6.8 millimeters mercury Standard Deviation 10.33
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 8	-0.8 millimeters mercury Standard Deviation 7.48	-0.3 millimeters mercury Standard Deviation 10.55
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 15	1.5 millimeters mercury Standard Deviation 9.58	-0.8 millimeters mercury Standard Deviation 9.34
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 22	-0.3 millimeters mercury Standard Deviation 6.01	-2.3 millimeters mercury Standard Deviation 10.52
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 43	5.4 millimeters mercury Standard Deviation 12.47	4.6 millimeters mercury Standard Deviation 8.27
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 50	10.6 millimeters mercury Standard Deviation 9.78	6.6 millimeters mercury Standard Deviation 12.58
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 64	4.3 millimeters mercury Standard Deviation 10.41	0.1 millimeters mercury Standard Deviation 14.84
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 8	3.8 millimeters mercury Standard Deviation 9.12	6.3 millimeters mercury Standard Deviation 10.52
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 15	4.5 millimeters mercury Standard Deviation 15.62	2.7 millimeters mercury Standard Deviation 10.97
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 22	2.7 millimeters mercury Standard Deviation 9.30	3.0 millimeters mercury Standard Deviation 13.03
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 29	8.2 millimeters mercury Standard Deviation 10.70	1.2 millimeters mercury Standard Deviation 9.06
Mean Change From Baseline in Vital Signs: Blood Pressure Systolic- Day 36	8.5 millimeters mercury Standard Deviation 12.93	3.2 millimeters mercury Standard Deviation 5.41
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 29	4.0 millimeters mercury Standard Deviation 8.95	-4.4 millimeters mercury Standard Deviation 11.89
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 36	3.6 millimeters mercury Standard Deviation 11.73	-0.3 millimeters mercury Standard Deviation 6.80
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 43	2.9 millimeters mercury Standard Deviation 6.95	-5.1 millimeters mercury Standard Deviation 10.09
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 50	4.7 millimeters mercury Standard Deviation 7.38	-0.5 millimeters mercury Standard Deviation 16.39
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 64	3.1 millimeters mercury Standard Deviation 4.77	-4.7 millimeters mercury Standard Deviation 8.96
Mean Change From Baseline in Vital Signs: Blood Pressure Diastolic- Day 78	1.7 millimeters mercury Standard Deviation 7.28	-3.5 millimeters mercury Standard Deviation 10.41