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

• ClinicalTrials.gov Identifier: NCT02965573
• Recruitment Status: Completed
• First Posted: November 17, 2016
• Results First Posted: January 8, 2021
• Last Update Posted: January 8, 2021
• Sponsor: argenx
• Collaborator: Quintiles, Inc.
• Information provided by (Responsible Party): argenx

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Myasthenia Gravis
• Interventions: Biological: ARGX-113; Drug: Placebo
• Enrollment: 24

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 at a dose of 10 mg/kg in 4 intravenous (IV) infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Period Title: Overall Study
Started	12	12
Completed	11	12
Not Completed	1	0
Reason Not Completed
Lack of Efficacy	1	0

Baseline Characteristics

Arm/Group Title		ARGX-113	Placebo	Total
Arm/Group Description		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.	Total of all reporting groups
Overall Number of Baseline Participants		12	12	24
Baseline Analysis Population Description		Baseline characteristics are summarized for the randomized population which included patients who had been allocated to a randomized treatment group, regardless of whether they received the planned treatment or not.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	8 66.7%	10 83.3%	18 75.0%
	>=65 years	4 33.3%	2 16.7%	6 25.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	12 participants	12 participants	24 participants
		55.3 (13.60)	43.5 (19.28)	49.4 (17.39)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	Female	7 58.3%	8 66.7%	15 62.5%
	Male	5 41.7%	4 33.3%	9 37.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	11 91.7%	12 100.0%	23 95.8%
	Unknown or Not Reported	1 8.3%	0 0.0%	1 4.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 8.3%	0 0.0%	1 4.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	1 8.3%	1 4.2%
	White	11 91.7%	11 91.7%	22 91.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Body Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	12 participants	12 participants	24 participants
		74.08 (15.477)	75.21 (14.343)	74.64 (14.604)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs)
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
At least 1 TEAE	10 83.3%	10 83.3%
At least 1 treatment-related TEAE	8 66.7%	3 25.0%
At least 1 treatment emergent SAE	0 0.0%	0 0.0%
Withdrawn from treatment with at least 1 TEAE	0 0.0%	0 0.0%
Discontinued study due to at least 1 TEAE	0 0.0%	0 0.0%
NCI-CTCAE severity Grade ≥3	0 0.0%	0 0.0%
Number of Deaths	0 0.0%	0 0.0%

2. Primary Outcome

Title	Mean Change From Baseline in Vital Signs: Blood Pressure
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: millimeters mercury
Systolic- Day 8	Number Analyzed	12 participants	12 participants
		3.8 (9.12)	6.3 (10.52)
Systolic- Day 15	Number Analyzed	12 participants	12 participants
		4.5 (15.62)	2.7 (10.97)
Systolic- Day 22	Number Analyzed	12 participants	12 participants
		2.7 (9.30)	3.0 (13.03)
Systolic- Day 29	Number Analyzed	12 participants	11 participants
		8.2 (10.70)	1.2 (9.06)
Systolic- Day 36	Number Analyzed	12 participants	12 participants
		8.5 (12.93)	3.2 (5.41)
Systolic- Day 43	Number Analyzed	12 participants	11 participants
		5.4 (12.47)	4.6 (8.27)
Systolic- Day 50	Number Analyzed	11 participants	10 participants
		10.6 (9.78)	6.6 (12.58)
Systolic- Day 64	Number Analyzed	10 participants	12 participants
		4.3 (10.41)	0.1 (14.84)
Systolic- Day 78	Number Analyzed	11 participants	12 participants
		2.5 (10.82)	6.8 (10.33)
Diastolic- Day 8	Number Analyzed	12 participants	12 participants
		-0.8 (7.48)	-0.3 (10.55)
Diastolic- Day 15	Number Analyzed	12 participants	12 participants
		1.5 (9.58)	-0.8 (9.34)
Diastolic- Day 22	Number Analyzed	12 participants	12 participants
		-0.3 (6.01)	-2.3 (10.52)
Diastolic- Day 29	Number Analyzed	12 participants	11 participants
		4.0 (8.95)	-4.4 (11.89)
Diastolic- Day 36	Number Analyzed	12 participants	12 participants
		3.6 (11.73)	-0.3 (6.80)
Diastolic- Day 43	Number Analyzed	12 participants	11 participants
		2.9 (6.95)	-5.1 (10.09)
Diastolic- Day 50	Number Analyzed	11 participants	10 participants
		4.7 (7.38)	-0.5 (16.39)
Diastolic- Day 64	Number Analyzed	10 participants	12 participants
		3.1 (4.77)	-4.7 (8.96)
Diastolic- Day 78	Number Analyzed	11 participants	12 participants
		1.7 (7.28)	-3.5 (10.41)

3. Primary Outcome

Title	Mean Change From Baseline in Vital Signs: Heart Rate
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: beats/minute
Day 8	Number Analyzed	12 participants	12 participants
		-2.7 (11.80)	1.8 (11.66)
Day 15	Number Analyzed	12 participants	12 participants
		-4.1 (9.05)	2.5 (12.40)
Day 22	Number Analyzed	12 participants	12 participants
		-0.8 (10.70)	-1.1 (12.15)
Day 29	Number Analyzed	12 participants	11 participants
		-2.4 (13.49)	0.1 (9.75)
Day 36	Number Analyzed	12 participants	12 participants
		1.1 (14.08)	3.1 (11.87)
Day 43	Number Analyzed	12 participants	11 participants
		0.2 (10.79)	3.1 (15.49)
Day 50	Number Analyzed	11 participants	10 participants
		0.5 (19.82)	2.1 (12.98)
Day 64	Number Analyzed	10 participants	12 participants
		-4.0 (19.22)	0.6 (8.71)
Day 78	Number Analyzed	11 participants	12 participants
		-3.1 (10.78)	-2.0 (15.12)

4. Primary Outcome

Title	Mean Change From Baseline in Vital Signs: Temperature
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: degrees Centigrade
Day 8	Number Analyzed	12 participants	12 participants
		0.18 (0.493)	0.15 (0.511)
Day 15	Number Analyzed	12 participants	12 participants
		0.09 (0.535)	0.16 (0.382)
Day 22	Number Analyzed	12 participants	12 participants
		0.05 (0.613)	0.27 (0.429)
Day 29	Number Analyzed	12 participants	11 participants
		-0.03 (0.459)	0.11 (0.291)
Day 36	Number Analyzed	12 participants	12 participants
		-0.13 (0.620)	0.09 (0.334)
Day 43	Number Analyzed	12 participants	11 participants
		-0.04 (0.563)	0.08 (0.299)
Day 50	Number Analyzed	11 participants	10 participants
		-0.03 (0.341)	0.10 (0.422)
Day 64	Number Analyzed	9 participants	12 participants
		0.21 (0.593)	0.17 (0.306)
Day 78	Number Analyzed	11 participants	12 participants
		0.11 (0.552)	0.18 (0.282)

5. Primary Outcome

Title	Mean Change From Baseline in Vital Signs: Weight
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: kg
Day 8	Number Analyzed	12 participants	12 participants
		0.18 (0.443)	-0.02 (1.359)
Day 15	Number Analyzed	12 participants	12 participants
		0.60 (0.768)	0.31 (1.528)
Day 22	Number Analyzed	12 participants	12 participants
		0.54 (0.672)	0.01 (1.672)
Day 29	Number Analyzed	12 participants	11 participants
		0.41 (0.729)	-0.04 (1.826)
Day 36	Number Analyzed	12 participants	12 participants
		0.76 (0.840)	-0.02 (1.770)
Day 43	Number Analyzed	12 participants	11 participants
		0.91 (2.093)	0.31 (2.593)
Day 50	Number Analyzed	11 participants	9 participants
		0.48 (1.156)	0.44 (1.996)
Day 64	Number Analyzed	10 participants	12 participants
		0.26 (1.052)	-0.27 (2.703)
Day 78	Number Analyzed	11 participants	12 participants
		0.23 (1.238)	-0.60 (3.122)

6. Primary Outcome

Title	Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

7. Primary Outcome

Title	Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
B-lymphocyte count decreased	2 16.7%	0 0.0%
T-lymphocyte count decreased	1 8.3%	0 0.0%
Lymphocyte count decreased	2 16.7%	0 0.0%
Monocyte count decreased	2 16.7%	0 0.0%
Neutrophil count inceased	2 16.7%	0 0.0%
Blood thyroid stimulating hormone increased	1 8.3%	0 0.0%

8. Secondary Outcome

Title	Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
Day 8	Number Analyzed	12 participants	12 participants
		-1.9 (2.75)	-0.7 (1.56)
Day 15	Number Analyzed	12 participants	12 participants
		-2.8 (2.70)	-2.2 (2.08)
Day 22	Number Analyzed	12 participants	12 participants
		-3.5 (2.84)	-2.5 (2.50)
Day 29	Number Analyzed	12 participants	11 participants
		-4.1 (2.64)	-2.3 (2.72)
Day 36	Number Analyzed	12 participants	12 participants
		-4.2 (3.30)	-2.1 (2.43)
Day 43	Number Analyzed	12 participants	11 participants
		-3.8 (2.72)	-2.4 (2.69)
Day 50	Number Analyzed	11 participants	10 participants
		-4.4 (3.53)	-2.9 (2.96)
Day 64	Number Analyzed	10 participants	12 participants
		-3.4 (3.27)	-1.8 (3.55)
Day 78	Number Analyzed	11 participants	12 participants
		-3.5 (3.50)	-1.8 (4.22)

9. Secondary Outcome

Title	Mean Change From Baseline in QMG Score
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
Day 8	Number Analyzed	12 participants	12 participants
		-2.8 (3.13)	0.0 (2.22)
Day 15	Number Analyzed	12 participants	12 participants
		-4.0 (4.29)	-1.8 (3.08)
Day 22	Number Analyzed	12 participants	12 participants
		-4.0 (4.55)	-1.8 (3.91)
Day 29	Number Analyzed	12 participants	11 participants
		-4.9 (4.94)	-1.4 (3.72)
Day 36	Number Analyzed	12 participants	12 participants
		-5.7 (5.97)	-1.9 (3.37)
Day 43	Number Analyzed	12 participants	11 participants
		-4.6 (5.73)	-2.1 (4.55)
Day 50	Number Analyzed	10 participants	9 participants
		-5.5 (5.84)	-2.1 (3.95)
Day 64	Number Analyzed	10 participants	10 participants
		-4.5 (6.42)	-1.8 (4.59)
Day 78	Number Analyzed	10 participants	10 participants
		-4.8 (7.67)	-2.1 (5.07)

10. Secondary Outcome

Title	Mean Change From Baseline in MGC Score
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
Day 8	Number Analyzed	12 participants	12 participants
		-4.3 (5.87)	-1.3 (2.77)
Day 15	Number Analyzed	12 participants	12 participants
		-5.8 (6.45)	-4.4 (4.56)
Day 22	Number Analyzed	12 participants	12 participants
		-7.8 (6.92)	-4.0 (3.86)
Day 29	Number Analyzed	12 participants	11 participants
		-8.7 (7.36)	-4.1 (5.22)
Day 36	Number Analyzed	12 participants	12 participants
		-9.0 (8.73)	-4.1 (5.58)
Day 43	Number Analyzed	12 participants	11 participants
		-8.6 (8.54)	-3.5 (5.97)
Day 50	Number Analyzed	11 participants	10 participants
		-9.4 (7.92)	-4.2 (5.51)
Day 64	Number Analyzed	10 participants	12 participants
		-7.2 (8.65)	-3.8 (6.84)
Day 78	Number Analyzed	11 participants	12 participants
		-7.1 (9.71)	-3.8 (6.83)

11. Secondary Outcome

Title	Mean Change From Baseline in MGQoL15r Score
Description	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.
Time Frame	Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113	Placebo
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
Day 8	Number Analyzed	12 participants	12 participants
		-2.0 (5.77)	-0.8 (1.86)
Day 15	Number Analyzed	12 participants	12 participants
		-3.7 (4.42)	-1.0 (2.76)
Day 22	Number Analyzed	12 participants	11 participants
		-4.3 (4.77)	-1.5 (3.17)
Day 29	Number Analyzed	11 participants	11 participants
		-4.7 (5.44)	-1.5 (2.91)
Day 36	Number Analyzed	11 participants	12 participants
		-6.0 (5.78)	-2.1 (3.58)
Day 43	Number Analyzed	12 participants	11 participants
		-5.3 (5.59)	-1.4 (3.70)
Day 50	Number Analyzed	11 participants	10 participants
		-4.4 (4.13)	-1.8 (3.71)
Day 64	Number Analyzed	10 participants	12 participants
		-3.7 (5.10)	-1.3 (3.68)
Day 78	Number Analyzed	11 participants	12 participants
		-2.7 (5.44)	-1.5 (3.61)

12. Secondary Outcome

Title	Maximum Reduction From Baseline in MG-ADL Score
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-5.1 (3.32)	-3.7 (2.93)

13. Secondary Outcome

Title	Maximum Reduction From Baseline in QMG Score
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-7.3 (6.08)	-4.3 (4.16)

14. Secondary Outcome

Title	Maximum Reduction From Baseline in MGC Score
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-11.5 (7.61)	-7.7 (4.40)

15. Secondary Outcome

Title	Maximum Reduction From Baseline in MGQoL15r Score
Description	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.
Time Frame	Day 1 to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-7.2 (5.42)	-3.0 (3.16)

16. Secondary Outcome

Title	Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113
Description	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.
Time Frame	Days 1, 8, 15 and 22

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		ARGX-113
Arm/Group Description:		Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed		12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms/milliliter (ng/mL)
Cmax - Day 1	Number Analyzed	12 participants
		179063.7; (31.9%)
Cmax - Day 8	Number Analyzed	11 participants
		173960.4; (19.5%)
Cmax - Day 15	Number Analyzed	11 participants
		153257.2; (22.1%)
Cmax - Day 22	Number Analyzed	11 participants
		162655.6; (26.1%)
Ctrough - Day 1	Number Analyzed	12 participants
		7266.2; (43.5%)
Ctrough - Day 8	Number Analyzed	11 participants
		9894.8; (54.7%)
Ctrough - Day 15	Number Analyzed	11 participants
		10045.5; (56.7%)
Ctrough - Day 22	Number Analyzed	11 participants
		10944.6; (71.1%)

17. Secondary Outcome

Title	PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113
Description	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.
Time Frame	Days 1, 8 15 and 22.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12
Median (Full Range); Unit of Measure: hours
Day 1	2.44; (2.08 to 2.58)
Day 8	2.50; (2.08 to 2.50)
Day 15	2.50; (2.07 to 2.50)
Day 22	2.46; (2.08 to 2.67)

18. Secondary Outcome

Title	PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113
Description	The t1/2 lambda z was calculated at Day 22.
Time Frame	Day 22

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	116.08; (15.8%)

19. Secondary Outcome

Title	PK Parameters - Accumulation Ratio (Rac) of ARGX-113
Description	The Rac was calculated as Day 22 Cmax/Day 1 Cmax.
Time Frame	Days 1 and 22.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	11
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
	0.9360; (25.7%)

20. Secondary Outcome

Title	Mean Percent Change From Baseline in Immunoglobulins (IgGs)
Description	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.
Time Frame	Baseline, Days 22 and 78

Outcome Measure Data

Analysis Population Description

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.

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

21. Secondary Outcome

Title	Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies
Description	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.
Time Frame	Baseline, Days 22 and 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: percentage change
Day 22	-52.2686 (26.32992)	-0.3236 (8.50886)
Day 78	-1.3361 (34.33867)	-7.8881 (33.43325)

22. Secondary Outcome

Title	Number of Patients With an Anti-drug Antibodies (ADA) Response
Description	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.
Time Frame	Baseline up to Day 78

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description:	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.	Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
Overall Number of Participants Analyzed	12	12
Measure Type: Number; Unit of Measure: participants
Patients with pre-dose ADA titers	4	2
Patients with post-dose ADA titers	4	3

Adverse Events

Time Frame	Day 1 to Day 78.
Adverse Event Reporting Description	TEAEs were monitored continuously from Day 1 until last study-related activity. In case of early discontinuation, any TEAEs were assessed for 30 days following the patient's last visit or until satisfactory resolution or stabilization. The safety analysis set included 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.
Arm/Group Title	ARGX-113		Placebo
Arm/Group Description	Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC.		Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC.
All-Cause Mortality
	ARGX-113		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/12 (0.00%)		0/12 (0.00%)
Serious Adverse Events
	ARGX-113		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	ARGX-113		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.33%)		10/12 (83.33%)
Gastrointestinal disorders
Abdominal pain upper † 1	1/12 (8.33%)	1	1/12 (8.33%)	1
Diarrhoea † 1	1/12 (8.33%)	1	1/12 (8.33%)	3
Nausea † 1	1/12 (8.33%)	1	1/12 (8.33%)	1
Toothache † 1	0/12 (0.00%)	0	2/12 (16.67%)	2
Abdominal pain † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Dyspepsia † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Flatulence † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Hypoaesthesia oral † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
General disorders
Asthenia † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Chills † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Feeling hot † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Influenza like illness † 1	0/12 (0.00%)	0	1/12 (8.33%)	2
Infusion site pain † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Infusion site pruritus † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Non-cardiac chest pain † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Pyrexia † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Infections and infestations
Tooth abscess † 1	0/12 (0.00%)	0	2/12 (16.67%)	3
Gingivitis † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Herpes zoster † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Nasopharyngitis † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Pharyngitis † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Viral upper respiratory tract infection † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Injury, poisoning and procedural complications
Contusion † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Ligament sprain † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Muscle rupture † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Post-traumatic pain † 1	0/12 (0.00%)	0	1/12 (8.33%)	2
Road traffic accident † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Investigations
B-lymphocyte count decreased † 1	2/12 (16.67%)	3	0/12 (0.00%)	0
Lymphocyte count decreased † 1	2/12 (16.67%)	4	0/12 (0.00%)	0
Monocyte count decreased † 1	2/12 (16.67%)	4	0/12 (0.00%)	0
Neutrophil count increased † 1	2/12 (16.67%)	4	0/12 (0.00%)	0
Blood thyroid stimulating hormone increased † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
T-lymphocyte count decreased † 1	1/12 (8.33%)	2	0/12 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/12 (0.00%)	0	2/12 (16.67%)	2
Myalgia † 1	2/12 (16.67%)	2	0/12 (0.00%)	0
Muscular weakness † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Pain in extremity † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Nervous system disorders
Headache † 1	4/12 (33.33%)	9	3/12 (25.00%)	5
Dizziness † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Paraesthesia † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Post herpetic neuralgia † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Reproductive system and breast disorders
Dysmenorrhoea † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Premenstrual headache † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea † 1	1/12 (8.33%)	2	1/12 (8.33%)	1
Cough † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
Epistaxis † 1	0/12 (0.00%)	0	1/12 (8.33%)	3
Oropharyngeal pain † 1	1/12 (8.33%)	1	0/12 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	1/12 (8.33%)	1	2/12 (16.67%)	2
Erythema † 1	0/12 (0.00%)	0	1/12 (8.33%)	1
1 Term from vocabulary, MedDRA (19.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Regulatory Manager
• Organization: argenx BVBA
• Phone: +32 93103400
• EMail: regulatory@argenx.com

• Responsible Party: argenx
• ClinicalTrials.gov Identifier: NCT02965573
• Other Study ID Numbers: ARGX-113-1602; 2016-002938-73 ( EudraCT Number )
• First Submitted: October 20, 2016
• First Posted: November 17, 2016
• Results First Submitted: November 18, 2020
• Results First Posted: January 8, 2021
• Last Update Posted: January 8, 2021