Myasthenia Gravis
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter Phase II study to evaluate the safety, efficacy, and pharmacokinetics of ARGX-113 for the treatment of autoimmune Myasthenia Gravis (MG) with generalized muscle weakness.
Detailed description
Myasthenia Gravis (MG) is an autoimmune disorder characterized in most cases by T cell and antibody responses to neuromuscular junction proteins such as skeletal muscle nicotinic acetylcholine receptor (AChR). Antibodies against epitopes of the AChR of the neuromuscular junction cause failure of neuromuscular transmission, resulting in the characteristic fatigue and weakness associated with this severe disorder. The study will evaluate an innovative candidate in MG.
Interventions
BIOLOGICALARGX-113
DRUGPlacebo
Sponsors
Quintiles, Inc.
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits). 2. Male or female patients aged ≥18 years. 3. Diagnosis of autoimmune MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II, III, or IVa, and likely not in need of a respirator for the duration of the study as judged by the Investigator. The confirmation of the diagnosis should be documented and supported by: * Positive serologic test for anti-AChR antibodies before Screening and * at least 1 of the following 3 tests: (i) History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation or (ii) History of positive edrophonium chloride test, or (iii) Patient has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician. 4. A total score of ≥ 5 on the MG ADL at Screening and Baseline with more than 50% of this score attributed to non ocular items. 5. Patients are required to be on a stable dose of their MG treatment prior to randomization. For patients receiving AZA, other NSIDs, steroids, and/or cholinesterase inhibitors as concomitant medications the following conditions will apply: * AZA: treatment initiated at least 12 months ago and no dose changes in the last 6 months before screening. * Other NSIDs (e.g., methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide) treatment initiated at least 6 months ago and no dose changes in the last 3 months before Screening. * Steroids treatment initiated at least 3 months prior to and no dose changes in the last month before Screening. * Cholinesterase inhibitors: to be on a stable dose for \>2 weeks before Screening. Note: cholinesterase inhibitors must be held for at least 12 hours consistent with the revised manual for the QMG test as recommended by the Myasthenia Gravis Foundation of America Inc (MGFA), before the MGQoL15r, MG-ADL, QMG, and MGC assessments. 6. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Visit 1 prior to administration of IMP. Female of childbearing potential are defined as all female participants unless they are postmenopausal (defined by continuous amenorrhea) for at least 2 years with a Follicle stimulating hormone (FSH) \> 40 IU/L or are surgically sterile (i.e., who had a hysterectomy, bilateral oophorectomy, or have current documented tubal ligation or any other permanent female sterilization procedure). Determination of FSH levels can be used to confirm postmenopausal status in amenorrheic patients not on hormonal replacement therapy if the test result is within the postmenopausal range per the central laboratory. 7. Female participants of childbearing potential must agree to use a highly effective method of contraception (i.e., pregnancy rate of less than 1% per year) during the study and for 90 days after the discontinuation of the IMP. Adequate contraceptive methods include combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS), true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female participant who is not of childbearing potential. Female participants and female partners of male study participants using a hormonal contraceptive must also use a barrier method (i.e., condom or occlusive cap \[diaphragm or cervical/vault caps\]) and should have been stable on their hormonal contraceptive treatment for at least 4 weeks before Screening. 8. Sterilized male patients who have had vasectomy with documented aspermia post procedure can be included. In addition, male patients must be advised not to donate sperm during this period from signing of Informed Consent Form (ICF), throughout the duration of the study, and for 90 days after the last administration of IMP. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective method of double barrier contraception (e.g., condom with spermicidal cream or jelly, 1 hormonal plus 1 barrier method or 2 simultaneous barrier methods). Male patients practicing true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) can be included.
Exclusion criteria
1. Females who are pregnant or lactating. 2. MGFA Class I, IVb, and V. 3. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Screening; or history of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Patients must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies, and a negative QuantiFERON®-TB Gold test at Screening. Patients with an indeterminate QuantiFERON®-TB Gold test result will be allowed one retest; if not negative on retesting, the patient will be excluded. 4. At Screening, have clinically significant laboratory abnormalities or as below: * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN). * Total serum bilirubin of \> 1.5 x ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome). * Serum creatinine \> 1.5 mg/dL and creatinine clearance \< 50 ml/min (using the Chronic Kidney Disease Epidemiology \[CKD-EPI\]-Creatinine formula). * Clinically Significant proteinuria (i.e., \> 3 x ULN). * Hemoglobin ≤ 9 g/L. * Thyroid stimulating hormone or thyroglobulin outside of the central laboratory normal range. * International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \> 1.2 x ULN. * Total immunoglobulin G level \< 6 g/L. 5. Body Mass Index (BMI) at Screening ≥ 35 kg/m2. 6. Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal range per the central laboratory at Screening. 7. Use of any biological therapy or investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) before Screening. 8. Immunoglobulins given by IV (IVIg), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening. 9. Have known autoimmune disease other than MG that would interfere with the course and conduct of the study (such as uncontrolled thyroid disease or severe RA). 10. Have received vaccinations within 4 weeks before Screening or have any vaccinations planned during the study. 11. Have a history of malignancy, including malignant thymoma, or myeloproliferative or lymphoproliferative disorders at any time, unless deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening. Patients with completely excised nonmelanoma skin cancers (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. 12. Have a history of cerebrovascular accident or myocardial infarction within the last 12 months before Screening, or current severe/unstable angina, arrhythmia, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV, or uncontrolled hypertension. 13. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious diseases) which, in the opinion of the Investigator, could confound the results of the study or put the patient at undue risk. 14. Major past surgery (e.g., heart valve replacement, hip replacement) that, in the opinion of the Investigator, poses a risk to patient's safety or interferes with the study evaluation, procedures or completion. 15. Thymectomy when performed \< 3 months prior to Screening. 16. History or presence of alcoholism or drug/chemical/substance abuse within 2 years before Screening per Investigator's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | Day 1 to Day 78 | 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. |
| Mean Change From Baseline in Vital Signs: Blood Pressure | Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78 | 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. |
| Mean Change From Baseline in Vital Signs: Heart Rate | 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. |
| Mean Change From Baseline in Vital Signs: Temperature | 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. |
| Mean Change From Baseline in Vital Signs: Weight | 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. |
| Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters | Day 1 to Day 78 | 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. |
| Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Day 1 to Day 78 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Reduction From Baseline in MGQoL15r Score | 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. |
| Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | 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 mean maximum observed plasma concentration (Cmax) and plasma concentration observed pre-dose (Ctrough) is presented. |
| PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 | 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. |
| PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113 | Day 22 | The t1/2 lambda z was calculated at Day 22. |
| Maximum Reduction From Baseline in QMG Score | 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. |
| Mean Percent Change From Baseline in Immunoglobulins (IgGs) | Baseline, Days 22 and 78 | 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. |
| Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies | Baseline, Days 22 and 78 | 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. |
| Number of Patients With an Anti-drug Antibodies (ADA) Response | 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. |
| PK Parameters - Accumulation Ratio (Rac) of ARGX-113 | Days 1 and 22. | The Rac was calculated as Day 22 Cmax/Day 1 Cmax. |
| Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 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 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. |
| Mean Change From Baseline in QMG Score | Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 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 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. |
| Mean Change From Baseline in MGC Score | 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. |
| Mean Change From Baseline in MGQoL15r Score | 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. |
| Maximum Reduction From Baseline in MG-ADL Score | 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. |
| Maximum Reduction From Baseline in MGC Score | 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. |
Countries
Belgium, Canada, Italy, Netherlands, Poland, Spain, Sweden, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| ARGX-113 Patients received ARGX-113 at a dose of 10 mg/kg in 4 IV infusions, administered 1 week apart, in addition to SoC. | 12 |
| Placebo Patients received matching placebo in 4 IV infusions, administered 1 week apart, in addition to SoC. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | ARGX-113 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 10 Participants | 18 Participants |
| Age, Continuous | 55.3 years STANDARD_DEVIATION 13.6 | 43.5 years STANDARD_DEVIATION 19.28 | 49.4 years STANDARD_DEVIATION 17.39 |
| Body Weight | 74.08 kg STANDARD_DEVIATION 15.477 | 75.21 kg STANDARD_DEVIATION 14.343 | 74.64 kg STANDARD_DEVIATION 14.604 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 10 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Mean Change From Baseline in Vital Signs: Blood Pressure
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 78 | 1.7 millimeters mercury | Standard Deviation 7.28 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 43 | 2.9 millimeters mercury | Standard Deviation 6.95 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 8 | 3.8 millimeters mercury | Standard Deviation 9.12 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 15 | 4.5 millimeters mercury | Standard Deviation 15.62 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 22 | 2.7 millimeters mercury | Standard Deviation 9.3 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 29 | 8.2 millimeters mercury | Standard Deviation 10.7 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 36 | 8.5 millimeters mercury | Standard Deviation 12.93 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 43 | 5.4 millimeters mercury | Standard Deviation 12.47 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 50 | 10.6 millimeters mercury | Standard Deviation 9.78 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 64 | 4.3 millimeters mercury | Standard Deviation 10.41 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 78 | 2.5 millimeters mercury | Standard Deviation 10.82 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 8 | -0.8 millimeters mercury | Standard Deviation 7.48 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 15 | 1.5 millimeters mercury | Standard Deviation 9.58 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 22 | -0.3 millimeters mercury | Standard Deviation 6.01 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 29 | 4.0 millimeters mercury | Standard Deviation 8.95 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 36 | 3.6 millimeters mercury | Standard Deviation 11.73 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 50 | 4.7 millimeters mercury | Standard Deviation 7.38 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 64 | 3.1 millimeters mercury | Standard Deviation 4.77 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 36 | -0.3 millimeters mercury | Standard Deviation 6.8 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 78 | 6.8 millimeters mercury | Standard Deviation 10.33 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 43 | -5.1 millimeters mercury | Standard Deviation 10.09 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 8 | 6.3 millimeters mercury | Standard Deviation 10.52 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 8 | -0.3 millimeters mercury | Standard Deviation 10.55 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 15 | 2.7 millimeters mercury | Standard Deviation 10.97 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 64 | -4.7 millimeters mercury | Standard Deviation 8.96 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 22 | 3.0 millimeters mercury | Standard Deviation 13.03 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 15 | -0.8 millimeters mercury | Standard Deviation 9.34 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 29 | 1.2 millimeters mercury | Standard Deviation 9.06 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 50 | -0.5 millimeters mercury | Standard Deviation 16.39 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 36 | 3.2 millimeters mercury | Standard Deviation 5.41 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 22 | -2.3 millimeters mercury | Standard Deviation 10.52 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 43 | 4.6 millimeters mercury | Standard Deviation 8.27 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 78 | -3.5 millimeters mercury | Standard Deviation 10.41 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 50 | 6.6 millimeters mercury | Standard Deviation 12.58 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Diastolic- Day 29 | -4.4 millimeters mercury | Standard Deviation 11.89 |
| Placebo | Mean Change From Baseline in Vital Signs: Blood Pressure | Systolic- Day 64 | 0.1 millimeters mercury | Standard Deviation 14.84 |
Primary
Mean Change From Baseline in Vital Signs: Heart Rate
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 15 | -4.1 beats/minute | Standard Deviation 9.05 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 43 | 0.2 beats/minute | Standard Deviation 10.79 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 29 | -2.4 beats/minute | Standard Deviation 13.49 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 50 | 0.5 beats/minute | Standard Deviation 19.82 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 22 | -0.8 beats/minute | Standard Deviation 10.7 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 64 | -4.0 beats/minute | Standard Deviation 19.22 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 36 | 1.1 beats/minute | Standard Deviation 14.08 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 78 | -3.1 beats/minute | Standard Deviation 10.78 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Heart Rate | Day 8 | -2.7 beats/minute | Standard Deviation 11.8 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 78 | -2.0 beats/minute | Standard Deviation 15.12 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 8 | 1.8 beats/minute | Standard Deviation 11.66 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 15 | 2.5 beats/minute | Standard Deviation 12.4 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 22 | -1.1 beats/minute | Standard Deviation 12.15 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 29 | 0.1 beats/minute | Standard Deviation 9.75 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 36 | 3.1 beats/minute | Standard Deviation 11.87 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 43 | 3.1 beats/minute | Standard Deviation 15.49 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 50 | 2.1 beats/minute | Standard Deviation 12.98 |
| Placebo | Mean Change From Baseline in Vital Signs: Heart Rate | Day 64 | 0.6 beats/minute | Standard Deviation 8.71 |
Primary
Mean Change From Baseline in Vital Signs: Temperature
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 15 | 0.09 degrees Centigrade | Standard Deviation 0.535 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 43 | -0.04 degrees Centigrade | Standard Deviation 0.563 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 29 | -0.03 degrees Centigrade | Standard Deviation 0.459 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 50 | -0.03 degrees Centigrade | Standard Deviation 0.341 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 22 | 0.05 degrees Centigrade | Standard Deviation 0.613 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 64 | 0.21 degrees Centigrade | Standard Deviation 0.593 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 36 | -0.13 degrees Centigrade | Standard Deviation 0.62 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 78 | 0.11 degrees Centigrade | Standard Deviation 0.552 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Temperature | Day 8 | 0.18 degrees Centigrade | Standard Deviation 0.493 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 78 | 0.18 degrees Centigrade | Standard Deviation 0.282 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 8 | 0.15 degrees Centigrade | Standard Deviation 0.511 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 15 | 0.16 degrees Centigrade | Standard Deviation 0.382 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 22 | 0.27 degrees Centigrade | Standard Deviation 0.429 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 29 | 0.11 degrees Centigrade | Standard Deviation 0.291 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 36 | 0.09 degrees Centigrade | Standard Deviation 0.334 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 43 | 0.08 degrees Centigrade | Standard Deviation 0.299 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 50 | 0.10 degrees Centigrade | Standard Deviation 0.422 |
| Placebo | Mean Change From Baseline in Vital Signs: Temperature | Day 64 | 0.17 degrees Centigrade | Standard Deviation 0.306 |
Primary
Mean Change From Baseline in Vital Signs: Weight
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 8 | 0.18 kg | Standard Deviation 0.443 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 36 | 0.76 kg | Standard Deviation 0.84 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 22 | 0.54 kg | Standard Deviation 0.672 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 50 | 0.48 kg | Standard Deviation 1.156 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 15 | 0.60 kg | Standard Deviation 0.768 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 64 | 0.26 kg | Standard Deviation 1.052 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 29 | 0.41 kg | Standard Deviation 0.729 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 78 | 0.23 kg | Standard Deviation 1.238 |
| ARGX-113 | Mean Change From Baseline in Vital Signs: Weight | Day 43 | 0.91 kg | Standard Deviation 2.093 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 78 | -0.60 kg | Standard Deviation 3.122 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 43 | 0.31 kg | Standard Deviation 2.593 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 8 | -0.02 kg | Standard Deviation 1.359 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 15 | 0.31 kg | Standard Deviation 1.528 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 22 | 0.01 kg | Standard Deviation 1.672 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 29 | -0.04 kg | Standard Deviation 1.826 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 36 | -0.02 kg | Standard Deviation 1.77 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 50 | 0.44 kg | Standard Deviation 1.996 |
| Placebo | Mean Change From Baseline in Vital Signs: Weight | Day 64 | -0.27 kg | Standard Deviation 2.703 |
Primary
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | B-lymphocyte count decreased | 2 Participants |
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | T-lymphocyte count decreased | 1 Participants |
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Lymphocyte count decreased | 2 Participants |
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Monocyte count decreased | 2 Participants |
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Neutrophil count inceased | 2 Participants |
| ARGX-113 | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Blood thyroid stimulating hormone increased | 1 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Neutrophil count inceased | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | B-lymphocyte count decreased | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Monocyte count decreased | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | T-lymphocyte count decreased | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs | Lymphocyte count decreased | 0 Participants |
Primary
Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARGX-113 | Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters | 0 Participants |
| Placebo | Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs)
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARGX-113 | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 treatment emergent SAE | 0 Participants |
| ARGX-113 | 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 |
| ARGX-113 | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 treatment-related TEAE | 8 Participants |
| ARGX-113 | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | NCI-CTCAE severity Grade ≥3 | 0 Participants |
| ARGX-113 | 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 |
| ARGX-113 | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | Number of Deaths | 0 Participants |
| ARGX-113 | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 TEAE | 10 Participants |
| Placebo | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | Number of Deaths | 0 Participants |
| Placebo | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 TEAE | 10 Participants |
| Placebo | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 treatment-related TEAE | 3 Participants |
| Placebo | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | At least 1 treatment emergent SAE | 0 Participants |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) | NCI-CTCAE severity Grade ≥3 | 0 Participants |
Secondary
Maximum Reduction From Baseline in MG-ADL Score
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | Maximum Reduction From Baseline in MG-ADL Score | -5.1 score on a scale | Standard Deviation 3.32 |
| Placebo | Maximum Reduction From Baseline in MG-ADL Score | -3.7 score on a scale | Standard Deviation 2.93 |
Secondary
Maximum Reduction From Baseline in MGC Score
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | Maximum Reduction From Baseline in MGC Score | -11.5 score on a scale | Standard Deviation 7.61 |
| Placebo | Maximum Reduction From Baseline in MGC Score | -7.7 score on a scale | Standard Deviation 4.4 |
Secondary
Maximum Reduction From Baseline in MGQoL15r Score
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | Maximum Reduction From Baseline in MGQoL15r Score | -7.2 score on a scale | Standard Deviation 5.42 |
| Placebo | Maximum Reduction From Baseline in MGQoL15r Score | -3.0 score on a scale | Standard Deviation 3.16 |
Secondary
Maximum Reduction From Baseline in QMG Score
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | Maximum Reduction From Baseline in QMG Score | -7.3 score on a scale | Standard Deviation 6.08 |
| Placebo | Maximum Reduction From Baseline in QMG Score | -4.3 score on a scale | Standard Deviation 4.16 |
Secondary
Mean Change From Baseline in MGC Score
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 36 | -9.0 score on a scale | Standard Deviation 8.73 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 22 | -7.8 score on a scale | Standard Deviation 6.92 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 43 | -8.6 score on a scale | Standard Deviation 8.54 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 15 | -5.8 score on a scale | Standard Deviation 6.45 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 50 | -9.4 score on a scale | Standard Deviation 7.92 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 64 | -7.2 score on a scale | Standard Deviation 8.65 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 29 | -8.7 score on a scale | Standard Deviation 7.36 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 78 | -7.1 score on a scale | Standard Deviation 9.71 |
| ARGX-113 | Mean Change From Baseline in MGC Score | Day 8 | -4.3 score on a scale | Standard Deviation 5.87 |
| Placebo | Mean Change From Baseline in MGC Score | Day 78 | -3.8 score on a scale | Standard Deviation 6.83 |
| Placebo | Mean Change From Baseline in MGC Score | Day 8 | -1.3 score on a scale | Standard Deviation 2.77 |
| Placebo | Mean Change From Baseline in MGC Score | Day 15 | -4.4 score on a scale | Standard Deviation 4.56 |
| Placebo | Mean Change From Baseline in MGC Score | Day 22 | -4.0 score on a scale | Standard Deviation 3.86 |
| Placebo | Mean Change From Baseline in MGC Score | Day 29 | -4.1 score on a scale | Standard Deviation 5.22 |
| Placebo | Mean Change From Baseline in MGC Score | Day 36 | -4.1 score on a scale | Standard Deviation 5.58 |
| Placebo | Mean Change From Baseline in MGC Score | Day 43 | -3.5 score on a scale | Standard Deviation 5.97 |
| Placebo | Mean Change From Baseline in MGC Score | Day 64 | -3.8 score on a scale | Standard Deviation 6.84 |
| Placebo | Mean Change From Baseline in MGC Score | Day 50 | -4.2 score on a scale | Standard Deviation 5.51 |
Secondary
Mean Change From Baseline in MGQoL15r Score
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 15 | -3.7 score on a scale | Standard Deviation 4.42 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 43 | -5.3 score on a scale | Standard Deviation 5.59 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 29 | -4.7 score on a scale | Standard Deviation 5.44 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 50 | -4.4 score on a scale | Standard Deviation 4.13 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 22 | -4.3 score on a scale | Standard Deviation 4.77 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 64 | -3.7 score on a scale | Standard Deviation 5.1 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 36 | -6.0 score on a scale | Standard Deviation 5.78 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 78 | -2.7 score on a scale | Standard Deviation 5.44 |
| ARGX-113 | Mean Change From Baseline in MGQoL15r Score | Day 8 | -2.0 score on a scale | Standard Deviation 5.77 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 78 | -1.5 score on a scale | Standard Deviation 3.61 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 8 | -0.8 score on a scale | Standard Deviation 1.86 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 15 | -1.0 score on a scale | Standard Deviation 2.76 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 22 | -1.5 score on a scale | Standard Deviation 3.17 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 29 | -1.5 score on a scale | Standard Deviation 2.91 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 36 | -2.1 score on a scale | Standard Deviation 3.58 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 43 | -1.4 score on a scale | Standard Deviation 3.7 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 50 | -1.8 score on a scale | Standard Deviation 3.71 |
| Placebo | Mean Change From Baseline in MGQoL15r Score | Day 64 | -1.3 score on a scale | Standard Deviation 3.68 |
Secondary
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 15 | -2.8 score on a scale | Standard Deviation 2.7 |
| ARGX-113 | 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 |
| ARGX-113 | 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 |
| ARGX-113 | 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 |
| ARGX-113 | 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 |
| ARGX-113 | 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 |
| ARGX-113 | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 36 | -4.2 score on a scale | Standard Deviation 3.3 |
| ARGX-113 | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 78 | -3.5 score on a scale | Standard Deviation 3.5 |
| ARGX-113 | 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 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 78 | -1.8 score on a scale | Standard Deviation 4.22 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 8 | -0.7 score on a scale | Standard Deviation 1.56 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 15 | -2.2 score on a scale | Standard Deviation 2.08 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 22 | -2.5 score on a scale | Standard Deviation 2.5 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 29 | -2.3 score on a scale | Standard Deviation 2.72 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 36 | -2.1 score on a scale | Standard Deviation 2.43 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 43 | -2.4 score on a scale | Standard Deviation 2.69 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 50 | -2.9 score on a scale | Standard Deviation 2.96 |
| Placebo | Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | Day 64 | -1.8 score on a scale | Standard Deviation 3.55 |
Secondary
Mean Change From Baseline in QMG Score
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 15 | -4.0 score on a scale | Standard Deviation 4.29 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 43 | -4.6 score on a scale | Standard Deviation 5.73 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 29 | -4.9 score on a scale | Standard Deviation 4.94 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 50 | -5.5 score on a scale | Standard Deviation 5.84 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 22 | -4.0 score on a scale | Standard Deviation 4.55 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 64 | -4.5 score on a scale | Standard Deviation 6.42 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 36 | -5.7 score on a scale | Standard Deviation 5.97 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 78 | -4.8 score on a scale | Standard Deviation 7.67 |
| ARGX-113 | Mean Change From Baseline in QMG Score | Day 8 | -2.8 score on a scale | Standard Deviation 3.13 |
| Placebo | Mean Change From Baseline in QMG Score | Day 78 | -2.1 score on a scale | Standard Deviation 5.07 |
| Placebo | Mean Change From Baseline in QMG Score | Day 8 | 0.0 score on a scale | Standard Deviation 2.22 |
| Placebo | Mean Change From Baseline in QMG Score | Day 15 | -1.8 score on a scale | Standard Deviation 3.08 |
| Placebo | Mean Change From Baseline in QMG Score | Day 22 | -1.8 score on a scale | Standard Deviation 3.91 |
| Placebo | Mean Change From Baseline in QMG Score | Day 29 | -1.4 score on a scale | Standard Deviation 3.72 |
| Placebo | Mean Change From Baseline in QMG Score | Day 36 | -1.9 score on a scale | Standard Deviation 3.37 |
| Placebo | Mean Change From Baseline in QMG Score | Day 43 | -2.1 score on a scale | Standard Deviation 4.55 |
| Placebo | Mean Change From Baseline in QMG Score | Day 50 | -2.1 score on a scale | Standard Deviation 3.95 |
| Placebo | Mean Change From Baseline in QMG Score | Day 64 | -1.8 score on a scale | Standard Deviation 4.59 |
Secondary
Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies | Day 22 | -52.2686 percentage change | Standard Deviation 26.32992 |
| ARGX-113 | Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies | Day 78 | -1.3361 percentage change | Standard Deviation 34.33867 |
| Placebo | Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies | Day 22 | -0.3236 percentage change | Standard Deviation 8.50886 |
| Placebo | Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies | Day 78 | -7.8881 percentage change | Standard Deviation 33.43325 |
Secondary
Mean Percent Change From Baseline in Immunoglobulins (IgGs)
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG1 - Day 22 | -65.5 percentage change | Standard Deviation 8.56 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | Total IgG - Day 78 | -20.4 percentage change | Standard Deviation 24.96 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG3 - Day 22 | -65.25 percentage change | Standard Deviation 10.045 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG1 - Day 78 | -16.0 percentage change | Standard Deviation 18.17 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG3 - Day 78 | -5.19 percentage change | Standard Deviation 18.422 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | Total IgG - Day 22 | -70.0 percentage change | Standard Deviation 10.96 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG4 - Day 22 | -49.48 percentage change | Standard Deviation 10.278 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG2 - Day 22 | -61.0 percentage change | Standard Deviation 6.73 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG4 - Day 78 | 4.16 percentage change | Standard Deviation 25.513 |
| ARGX-113 | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG2 - Day 78 | -34.9 percentage change | Standard Deviation 16.02 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG4 - Day 78 | 1.57 percentage change | Standard Deviation 16.73 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | Total IgG - Day 22 | -2.8 percentage change | Standard Deviation 15.34 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | Total IgG - Day 78 | 6.4 percentage change | Standard Deviation 27.49 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG1 - Day 22 | -2.1 percentage change | Standard Deviation 9.29 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG1 - Day 78 | -1.1 percentage change | Standard Deviation 19.01 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG2 - Day 22 | -4.4 percentage change | Standard Deviation 6.99 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG2 - Day 78 | -5.3 percentage change | Standard Deviation 17.63 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG3 - Day 22 | 0.57 percentage change | Standard Deviation 9.566 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG3 - Day 78 | 2.52 percentage change | Standard Deviation 15.341 |
| Placebo | Mean Percent Change From Baseline in Immunoglobulins (IgGs) | IgG4 - Day 22 | 0.79 percentage change | Standard Deviation 6.592 |
Secondary
Number of Patients With an Anti-drug Antibodies (ADA) Response
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARGX-113 | Number of Patients With an Anti-drug Antibodies (ADA) Response | Patients with pre-dose ADA titers | 4 participants |
| ARGX-113 | Number of Patients With an Anti-drug Antibodies (ADA) Response | Patients with post-dose ADA titers | 4 participants |
| Placebo | Number of Patients With an Anti-drug Antibodies (ADA) Response | Patients with pre-dose ADA titers | 2 participants |
| Placebo | Number of Patients With an Anti-drug Antibodies (ADA) Response | Patients with post-dose ADA titers | 3 participants |
Secondary
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Cmax - Day 22 | 162655.6 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26.1 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Ctrough - Day 1 | 7266.2 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 43.5 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Ctrough - Day 8 | 9894.8 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 54.7 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Ctrough - Day 15 | 10045.5 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 56.7 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Ctrough - Day 22 | 10944.6 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 71.1 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Cmax - Day 1 | 179063.7 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 31.9 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Cmax - Day 8 | 173960.4 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 19.5 |
| ARGX-113 | Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 | Cmax - Day 15 | 153257.2 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 22.1 |
Secondary
PK Parameters - Accumulation Ratio (Rac) of ARGX-113
The Rac was calculated as Day 22 Cmax/Day 1 Cmax.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | PK Parameters - Accumulation Ratio (Rac) of ARGX-113 | 0.9360 ratio | Geometric Coefficient of Variation 25.7 |
Secondary
PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113
The t1/2 lambda z was calculated at Day 22.
Time frame: Day 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ARGX-113 | PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113 | 116.08 hours | Geometric Coefficient of Variation 15.8 |
Secondary
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113
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.
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ARGX-113 | PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 | Day 1 | 2.44 hours |
| ARGX-113 | PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 | Day 8 | 2.50 hours |
| ARGX-113 | PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 | Day 15 | 2.50 hours |
| ARGX-113 | PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 | Day 22 | 2.46 hours |