ADAPT: An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness

• Sponsor: argenx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03669588
• Collaborator: (none)
• Enrollment: 167
• Locations: 66
• Arms: 2
• Actual Duration (Months): 19.5
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo controlled, multicenter Phase 3 trial to evaluate the efficacy, safety, tolerability, quality of life and impact on normal daily activities of ARGX-113 in patients with gMG.

Condition or Disease	Intervention/Treatment	Phase
Generalized Myasthenia Gravis	Biological: ARGX-113; Biological: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 167 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Trial to Evaluate the Efficacy, Safety and Tolerability of ARGX-113 in Patients With Myasthenia Gravis Having Generalized Muscle Weakness
• Actual Study Start Date: Aug 22, 2018
• Actual Primary Completion Date: Apr 6, 2020
• Actual Study Completion Date: Apr 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARGX-113	Biological: ARGX-113; Intravenous administration of ARGX-113; Other Names: efgartigimod
Placebo Comparator: Placebo	Biological: Placebo; Intravenous administration of placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population [Baseline up to Day 63 (end of TC1)]

   The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. The scale comprises 2 items on daily life activities and 6 items on symptoms. The MG-ADL total score range is 0-24, with higher scores indicative of greater disease severity. A patient was considered an MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to baseline of C1 [C1B]) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.

Secondary Outcome Measures

1. Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population [Baseline up to Day 63 (end of TC1)]

   The QMG scale quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG scale consists of 13 items that measure endurance or fatigability, and accounts for fluctuations in disease state. The QMG total score range is 0-39, with higher scores indicative of greater disease severity. A patient was considered a QMG responder during C1 if there was a reduction of ≥3-points on the QMG total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.

2. Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population [Baseline up to Day 63 (end of TC1)]

   The percentage of MG-ADL responders during C1 in the overall population is reported for this secondary end point; percentage of MG-ADL responders during C1 in the AChR-Ab seropositive population is reported previously as a primary end point.

3. Percentage of Time That Patients Had a Clinically Meaningful Improvement (CMI) in MG-ADL Total Score up to and Including Day 126; Analyzed in the AChR-Ab Seropositive Population [Baseline up to Day 126]

   An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).

4. Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population [Week 4 up to Day 182 (end of study [EoS])]

   Time to qualify for retreatment was defined as time from the Week 4 assessment until the first visit with a <2-point reduction compared to SEB in the MG-ADL total score and MG-ADL total score ≥5 points with >50% of the total score attributable to nonocular symptoms.

5. Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population [Baseline up to Day 63 (end of TC1)]

   A patient was considered an early MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than Week 2 (ie, after 1 or maximum 2 infusions of IMP in C1).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.

2. Male or female patients aged ≥ 18 years.

3. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb.

Other, more specific inclusion criteria are defined in the protocol

Exclusion Criteria:

1. Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.

2. Male patients who are sexually active and do not intend to use effective methods of contraception during the trial or within 90 days after the last dosing or male patients who plan to donate sperm during the trial or within 90 days after the last dosing.

3. MGFA Class I and V patients.

4. Patients with worsening muscle weakness secondary to concurrent infections or medications.

5. Patients with known seropositivity or who test positive for an active viral infection at Screening with:

• Hepatitis B Virus (HBV) (except patients who are seropositive because of HBV vaccination)

• Hepatitis C Virus (HCV)

• Human Immunodeficiency Virus (HIV)

Other, more specific exclusion criteria are further defined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 29	Phoenix	Arizona	United States	85018
2	Investigator Site 66	Carlsbad	California	United States	92011
3	Investigator Site 5	Los Angeles	California	United States	90033
4	Investigator Site 49	Los Angeles	California	United States	90095
5	Investigator Site 18	Orange	California	United States	92868
6	Investigator Site 40	Palo Alto	California	United States	94304
7	Investigator Site 59	San Francisco	California	United States	94115
8	Investigator Site 58	Aurora	Colorado	United States	80045
9	Investigator Site 34	Jacksonville	Florida	United States	32209
10	Investigator Site 4	Tampa	Florida	United States	33612
11	Investigator Site 30	Springfield	Illinois	United States	62702
12	Investigator Site 25	Iowa City	Iowa	United States	52242
13	Investigator Site 21	Kansas City	Kansas	United States	66160
14	Investigator Site 27	Boston	Massachusetts	United States	02115
15	Investigator Site 48	Detroit	Michigan	United States	48201
16	Investigator Site 53	Buffalo	New York	United States	14202
17	Investigator Site 3	Chapel Hill	North Carolina	United States	27599
18	Investigator Site 20	Cleveland	Ohio	United States	44195
19	Investigator Site 9	Portland	Oregon	United States	97239
20	Investigator Site 17	Charleston	South Carolina	United States	29425
21	Investigator Site	Cordova	Tennessee	United States	38018
22	Investigator Site 44	Houston	Texas	United States	77030
23	Investigator Site 6	San Antonio	Texas	United States	78229
24	Investigator Site 2	Charlottesville	Virginia	United States	22908
25	Investigator Site 16	Seattle	Washington	United States	98195
26	Investigator Site 11	Edegem		Belgium	2650
27	Investigator Site 8	Ghent		Belgium	9000
28	Investigator Site 38	Edmonton	Alberta	Canada	T6G 2G3
29	Investigator Site 24	Toronto	Ontario	Canada	M5G 2C4
30	Investigator Site 22	Montréal	Quebec	Canada	H3A 2B4
31	Investigator Site 32	Brno		Czechia	62500
32	Investigator Site 35	Ostrava-Poruba		Czechia	70852
33	Investigator Site 51	Praha 2		Czechia	128 00
34	Investigator Site 36	Aarhus		Denmark	8200
35	Investigator Site 15	Copenhagen		Denmark	2100
36	Investigator Site 13	Bordeaux Cedex		France	33076
37	Investigator Site 52	Marseille		France	13385
38	Investigator Site 46	Tbilisi		Georgia	0112
39	Investigator Site 45	Tbilisi		Georgia	0114
40	Investigator Site 47	Tbilisi		Georgia	0114
41	Investigator Site 33	Berlin		Germany	10117
42	Investigator Site 55	Budapest		Hungary	1204
43	Investigator Site 54	Szeged		Hungary	6725
44	Investigator Site 10	Milano		Italy	20133
45	Investigator Site 12	Napoli		Italy	80131
46	Investigator Site 42	Chiba-shi	Chiba	Japan	260-8677
47	Investigator Site 26	Sapporo	Hokkaido	Japan	0608543
48	Investigator Site 19	Hanamaki	Iwate	Japan	025-0075
49	Investigator Site 43	Sendai	Miyagi	Japan	983-8520
50	Investigator Site 50	Suita	Osaka	Japan	565-0871
51	Investigator Site 28	Ōsaka-sayama	Osaka	Japan	5898511
52	Investigator Site 31	Meguro	Tokyo	Japan	1538515
53	Investigator Site 41	Minato-Ku	Tokyo	Japan	108-8329
54	Investigator Site 39	Shinjuku-Ku	Tokyo	Japan	160-0023
55	Investigator Site 37	Leiden		Netherlands	2333 ZA
56	Investigator Site 7	Gdańsk		Poland	80-952
57	Investigator Site 57	Katowice		Poland	40-123
58	Investigator Site 14	Kraków		Poland	31-505
59	Investigator Site 23	Warszawa		Poland	02-097
60	Investigator Site 64	Krasnoyarsk		Russian Federation	660037
61	Investigator Site 62	Nizhny Novgorod		Russian Federation	603126
62	Investigator Site 65	Novosibirsk		Russian Federation	630087
63	Investigator Site 60	Samara		Russian Federation	443095
64	Investigator Site 61	Belgrade		Serbia	11000
65	Investigator Site 63	Edgbaston		United Kingdom	B15 2TH
66	Investigator Site 56	Liverpool		United Kingdom	L9 7LJ

Sponsors and Collaborators

• argenx

Investigators

• Study Director: Antonio Guglietta, MD, argenx

Study Documents (Full-Text)

• Study Protocol - Jul 11, 2019
• Statistical Analysis Plan - May 8, 2020

More Information

Publications

None provided.

• Responsible Party: argenx
• ClinicalTrials.gov Identifier: NCT03669588
• Other Study ID Numbers: ARGX-113-1704; 2018-002132-25
• First Posted: Sep 13, 2018
• Last Update Posted: Feb 8, 2022
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness; Paresis

Study Results

Participant Flow

Recruitment Details

Study was conducted in generalized myasthenia gravis (gMG) patients at 56 sites worldwide. Patients were randomized 1:1 within each stratum (Japanese/non-Japanese, acetylcholine receptor-antibody [AChR-Ab] status and standard of care [SoC; ie, concomitant gMG treatment]) to receive ARGX-113 intravenous (IV) 10 milligrams/kilogram (mg/kg) or placebo, in addition to SoC. Patients completing the study were eligible to roll over into a follow-up study ARGX-113-1705.

Pre-assignment Detail

Total study duration was up to 28 weeks, including a 2-week screening period, an initial 8-week treatment cycle (TC) and intertreatment cycle (ITC) of variable length depending on the patient. Patients had to be on a stable dose of SoC and not have received immunoglobulins by IV, subcutaneous or intramuscular route, or plasma exchange, < 1 month prior to screening. The study included both AChR-Ab seropositive and seronegative patients; AChR-Ab detection in serum was performed during screening.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle. Each 8-week TC comprised a 3-week treatment period and a 5-week follow-up period. At the end of each TC, patients entered the ITC period consisting of visits every 2 weeks. At each ITC visit, retreatment criteria were evaluated to determine if the patient was eligible to enter the next cycle for retreatment, based on clinical response as measured by the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle. Each 8-week TC comprised a 3-week treatment period and a 5-week follow-up period. At the end of each TC, patients entered the ITC period consisting of visits every 2 weeks. At each ITC visit, retreatment criteria were evaluated to determine if the patient was eligible to enter the next cycle for retreatment, based on clinical response as measured by the MG-ADL scale.
Period Title: Overall Study
STARTED	84	83
COMPLETED	80	76
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	ARGX-113	Placebo	Total
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Total of all reporting groups
Overall Participants	84	83	167
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.9 (14.41)	48.2 (14.97)	47.0 (14.69)
Age, Customized (Count of Participants)
18 - <65 years	73 86.9%	69 83.1%	142 85%
>= 65 years	11 13.1%	14 16.9%	25 15%
Sex: Female, Male (Count of Participants)
Female	63 75%	55 66.3%	118 70.7%
Male	21 25%	28 33.7%	49 29.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.4%	0 0%	2 1.2%
Asian	9 10.7%	7 8.4%	16 9.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 3.6%	3 3.6%	6 3.6%
White	69 82.1%	72 86.7%	141 84.4%
More than one race	1 1.2%	0 0%	1 0.6%
Unknown or Not Reported	0 0%	1 1.2%	1 0.6%
Race/Ethnicity, Customized (Count of Participants)
Japanese	8 9.5%	7 8.4%	15 9%
Hispanic or Latino	7 8.3%	2 2.4%	9 5.4%
Not Hispanic or Latino	69 82.1%	73 88%	142 85%
Not Reported	0 0%	1 1.2%	1 0.6%
Concomitant gMG treatment (Count of Participants)
Nonsteroidal Immunosuppressive Drugs (NSIDs)	51 60.7%	51 61.4%	102 61.1%
No NSIDs	33 39.3%	32 38.6%	65 38.9%
AChR-Ab status (Count of Participants)
Positive	65 77.4%	64 77.1%	129 77.2%
Negative	19 22.6%	19 22.9%	38 22.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population
Description	The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. The scale comprises 2 items on daily life activities and 6 items on symptoms. The MG-ADL total score range is 0-24, with higher scores indicative of greater disease severity. A patient was considered an MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to baseline of C1 [C1B]) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.
Time Frame	Baseline up to Day 63 (end of TC1)

Outcome Measure Data

Analysis Population Description

Analysis was performed in the AChR-Ab seropositive population using the modified intention-to-treat (mITT) analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	65	64
Number [percentage of patients]	67.7	29.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARGX-113, Placebo
	Comments	Analysis with a 2-sided exact test (using logistic regression) at the 2-sided 5% significance level in the AChR-Ab seropositive population, stratified by Japanese versus (vs) non-Japanese and NSID vs no NSID as concomitant gMG treatment, with cycle baseline MG-ADL total score as covariate. The treatment effect was presented as the odds ratio. An odds ratio of more than 1 represents a higher response rate for ARGX-113 compared to placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.951
	Confidence Interval	(2-Sided) 95%; 2.213 to 11.528
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population
Description	The QMG scale quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG scale consists of 13 items that measure endurance or fatigability, and accounts for fluctuations in disease state. The QMG total score range is 0-39, with higher scores indicative of greater disease severity. A patient was considered a QMG responder during C1 if there was a reduction of ≥3-points on the QMG total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.
Time Frame	Baseline up to Day 63 (end of TC1)

Outcome Measure Data

Analysis Population Description

Analysis was performed in the AChR-Ab seropositive population using the mITT analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	65	64
Number [percentage of patients]	63.1	14.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARGX-113, Placebo
	Comments	Analysis with a 2-sided exact test (using logistic regression) at the 2-sided 5% significance level in the AChR-Ab seropositive population, stratified by Japanese vs non-Japanese and NSID vs no NSID as concomitant gMG treatment, with cycle baseline QMG total score as covariate. The treatment effect was presented as the odds ratio. An odds ratio of more than 1 represents a higher response rate for ARGX-113 compared to placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	10.842
	Confidence Interval	(2-Sided) 95%; 4.179 to 31.200
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population
Description	The percentage of MG-ADL responders during C1 in the overall population is reported for this secondary end point; percentage of MG-ADL responders during C1 in the AChR-Ab seropositive population is reported previously as a primary end point.
Time Frame	Baseline up to Day 63 (end of TC1)

Outcome Measure Data

Analysis Population Description

Analysis was performed in the overall population (including both AChR-Ab seropositive and seronegative patients) using the mITT analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	84	83
Number [percentage of patients]	67.9	37.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARGX-113, Placebo
	Comments	Analysis with a 2-sided exact test (using logistic regression) at the 2-sided 5% significance level in the overall population, stratified by AChR-Ab status (seropositive vs seronegative), Japanese vs non-Japanese and NSID vs no NSID as concomitant gMG treatment, with cycle baseline MG-ADL total score as covariate. The treatment effect was presented as the odds ratio. An odds ratio of more than 1 represents a higher response rate for ARGX-113 compared to placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.699
	Confidence Interval	(2-Sided) 95%; 1.854 to 7.578
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Time That Patients Had a Clinically Meaningful Improvement (CMI) in MG-ADL Total Score up to and Including Day 126; Analyzed in the AChR-Ab Seropositive Population
Description	An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).
Time Frame	Baseline up to Day 126

Outcome Measure Data

Analysis Population Description

Analysis was performed in the AChR-Ab seropositive population using the mITT analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	65	64
Least Squares Mean (Standard Error) [percentage of time]	48.714 (6.163)	26.649 (6.316)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARGX-113, Placebo
	Comments	Analysis of covariance (ANCOVA) in the AChR-Ab seropositive population with treatment, baseline MG-ADL total score, Japanese vs non-Japanese, and NSID vs no NSID as concomitant gMG treatment as the covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	22.065
	Confidence Interval	(2-Sided) 95%; 10.949 to 33.181
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.616
	Estimation Comments

5. Secondary Outcome

Title	Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population
Description	Time to qualify for retreatment was defined as time from the Week 4 assessment until the first visit with a <2-point reduction compared to SEB in the MG-ADL total score and MG-ADL total score ≥5 points with >50% of the total score attributable to nonocular symptoms.
Time Frame	Week 4 up to Day 182 (end of study [EoS])

Outcome Measure Data

Analysis Population Description

Analysis was performed in the AChR-Ab seropositive population using the mITT analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	65	64
Median (95% Confidence Interval) [days]	35.0	8.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARGX-113, Placebo
	Comments	Analysis was performed in the AChR-Ab seropositive population and the p-value was calculated using the log-rank test, stratified by Japanese vs non-Japanese and NSID vs no NSID as concomitant gMG treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2604
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population
Description	A patient was considered an early MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than Week 2 (ie, after 1 or maximum 2 infusions of IMP in C1).
Time Frame	Baseline up to Day 63 (end of TC1)

Outcome Measure Data

Analysis Population Description

Analysis was performed in the AChR-Ab seropositive population using the mITT analysis set which included all randomized patients with a value for the MG-ADL total score at baseline and at least 1 postbaseline timepoint.

Arm/Group Title	ARGX-113	Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.	Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
Measure Participants	65	64
Number [percentage of patients]	56.9	25.0

Adverse Events

Time Frame	Treatment-emergent adverse events were monitored from first administration of IMP on Day 1 until the EoS (up to a maximum of approximately 182 days).
Adverse Event Reporting Description	The safety analysis set included patients in the randomized population who received at least a partial dose of IMP.
Arm/Group Title	ARGX-113		Placebo
Arm/Group Description	Patients received ARGX-113 IV 10 mg/kg administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.		Patients received matching placebo administered as a 1-hour infusion every 7 days for 4 infusions (Days 1, 8, 15, and 22) in each cycle.
All Cause Mortality
	ARGX-113		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/83 (0%)
Serious Adverse Events
	ARGX-113		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/84 (4.8%)		7/83 (8.4%)
Blood and lymphatic system disorders
Thrombocytosis	1/84 (1.2%)	1	0/83 (0%)	0
Cardiac disorders
Atrial fibrillation	0/84 (0%)	0	1/83 (1.2%)	1
Myocardial ischaemia	0/84 (0%)	0	1/83 (1.2%)	1
General disorders
Therapeutic product ineffective	0/84 (0%)	0	1/83 (1.2%)	1
Infections and infestations
Upper respiratory tract infection	0/84 (0%)	0	1/83 (1.2%)	1
Injury, poisoning and procedural complications
Procedural pain	0/84 (0%)	0	1/83 (1.2%)	1
Spinal compression fracture	0/84 (0%)	0	1/83 (1.2%)	1
Musculoskeletal and connective tissue disorders
Spinal ligament ossification	0/84 (0%)	0	1/83 (1.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenocarcinoma	1/84 (1.2%)	1	0/83 (0%)	0
Nervous system disorders
Myasthenia gravis	1/84 (1.2%)	1	2/83 (2.4%)	2
Myasthenia gravis crisis	0/84 (0%)	0	1/83 (1.2%)	1
Psychiatric disorders
Depression	1/84 (1.2%)	1	0/83 (0%)	0
Other (Not Including Serious) Adverse Events
	ARGX-113		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/84 (58.3%)		48/83 (57.8%)
Gastrointestinal disorders
Diarrhoea	6/84 (7.1%)	6	9/83 (10.8%)	14
Nausea	7/84 (8.3%)	7	9/83 (10.8%)	15
Infections and infestations
Bronchitis	5/84 (6%)	6	2/83 (2.4%)	2
Nasopharyngitis	10/84 (11.9%)	12	15/83 (18.1%)	17
Upper respiratory tract infection	9/84 (10.7%)	11	4/83 (4.8%)	4
Urinary tract infection	8/84 (9.5%)	9	4/83 (4.8%)	4
Musculoskeletal and connective tissue disorders
Myalgia	5/84 (6%)	6	1/83 (1.2%)	3
Nervous system disorders
Dizziness	3/84 (3.6%)	5	5/83 (6%)	5
Headache	24/84 (28.6%)	40	23/83 (27.7%)	39
Respiratory, thoracic and mediastinal disorders
Cough	3/84 (3.6%)	3	5/83 (6%)	5
Oropharyngeal pain	3/84 (3.6%)	3	7/83 (8.4%)	7
Vascular disorders
Hypertension	3/84 (3.6%)	4	6/83 (7.2%)	6

Limitations/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.