CClinicalTrials.gg
Sign In
CompletedNCT02965573Updated Aug 28, 2024Results posted

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

A Phase 2 interventional study of ARGX-113 and Placebo in Myasthenia Gravis, sponsored by argenx. Completed at 19 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-28.

Sponsored by argenx · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Myasthenia Gravis
03

In context

Myasthenia Gravis

324 studies on the registry are indexed under Myasthenia Gravis; 146 are open to participants now.

This study's enrollment of 24 is below the median of 44 across 212 interventional studies indexed under Myasthenia Gravis.

Browse Myasthenia Gravis studies →

Lead sponsor

argenx is the lead sponsor of 87 studies on the registry; 33 are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 16 (73%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
24 participants (actual)

Study arms

  • Active comparator
    ARGX-113

    During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive ARGX-113

    Biological: ARGX-113

  • Placebo comparator
    Placebo

    During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive placebo

    Drug: Placebo

Interventions

  • BiologicalARGX-113
  • DrugPlacebo
06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

07

Results

Posted Jan 8, 2021

Participant flow

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

Participant flow — Overall Study
MilestoneARGX-113Placebo
Started1212
Completed1112
Not completed10
Withdrew: Lack of efficacy10

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs)
ParticipantsARGX-113Placebo
At least 1 TEAE1010
At least 1 treatment-related TEAE83
At least 1 treatment emergent SAE00
Withdrawn from treatment with at least 1 TEAE00
Discontinued study due to at least 1 TEAE00
NCI-CTCAE severity Grade ≥300
Number of Deaths00
PrimaryMean 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
Reported as:
Mean · millimeters mercury
Mean Change From Baseline in Vital Signs: Blood Pressure
millimeters mercuryARGX-113Placebo
Systolic- Day 83.8 ± 9.126.3 ± 10.52
Systolic- Day 154.5 ± 15.622.7 ± 10.97
Systolic- Day 222.7 ± 9.303.0 ± 13.03
Systolic- Day 298.2 ± 10.701.2 ± 9.06
Systolic- Day 368.5 ± 12.933.2 ± 5.41
Systolic- Day 435.4 ± 12.474.6 ± 8.27
Systolic- Day 5010.6 ± 9.786.6 ± 12.58
Systolic- Day 644.3 ± 10.410.1 ± 14.84
Systolic- Day 782.5 ± 10.826.8 ± 10.33
Diastolic- Day 8-0.8 ± 7.48-0.3 ± 10.55
Diastolic- Day 151.5 ± 9.58-0.8 ± 9.34
Diastolic- Day 22-0.3 ± 6.01-2.3 ± 10.52
Diastolic- Day 294.0 ± 8.95-4.4 ± 11.89
Diastolic- Day 363.6 ± 11.73-0.3 ± 6.80
Diastolic- Day 432.9 ± 6.95-5.1 ± 10.09
Diastolic- Day 504.7 ± 7.38-0.5 ± 16.39
Diastolic- Day 643.1 ± 4.77-4.7 ± 8.96
Diastolic- Day 781.7 ± 7.28-3.5 ± 10.41
PrimaryMean 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
Reported as:
Mean · beats/minute
Mean Change From Baseline in Vital Signs: Heart Rate
beats/minuteARGX-113Placebo
Day 8-2.7 ± 11.801.8 ± 11.66
Day 15-4.1 ± 9.052.5 ± 12.40
Day 22-0.8 ± 10.70-1.1 ± 12.15
Day 29-2.4 ± 13.490.1 ± 9.75
Day 361.1 ± 14.083.1 ± 11.87
Day 430.2 ± 10.793.1 ± 15.49
Day 500.5 ± 19.822.1 ± 12.98
Day 64-4.0 ± 19.220.6 ± 8.71
Day 78-3.1 ± 10.78-2.0 ± 15.12
PrimaryMean 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
Reported as:
Mean · degrees Centigrade
Mean Change From Baseline in Vital Signs: Temperature
degrees CentigradeARGX-113Placebo
Day 80.18 ± 0.4930.15 ± 0.511
Day 150.09 ± 0.5350.16 ± 0.382
Day 220.05 ± 0.6130.27 ± 0.429
Day 29-0.03 ± 0.4590.11 ± 0.291
Day 36-0.13 ± 0.6200.09 ± 0.334
Day 43-0.04 ± 0.5630.08 ± 0.299
Day 50-0.03 ± 0.3410.10 ± 0.422
Day 640.21 ± 0.5930.17 ± 0.306
Day 780.11 ± 0.5520.18 ± 0.282
PrimaryMean 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
Reported as:
Mean · kg
Mean Change From Baseline in Vital Signs: Weight
kgARGX-113Placebo
Day 80.18 ± 0.443-0.02 ± 1.359
Day 150.60 ± 0.7680.31 ± 1.528
Day 220.54 ± 0.6720.01 ± 1.672
Day 290.41 ± 0.729-0.04 ± 1.826
Day 360.76 ± 0.840-0.02 ± 1.770
Day 430.91 ± 2.0930.31 ± 2.593
Day 500.48 ± 1.1560.44 ± 1.996
Day 640.26 ± 1.052-0.27 ± 2.703
Day 780.23 ± 1.238-0.60 ± 3.122
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters
ParticipantsARGX-113Placebo
Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters00
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs
ParticipantsARGX-113Placebo
B-lymphocyte count decreased20
T-lymphocyte count decreased10
Lymphocyte count decreased20
Monocyte count decreased20
Neutrophil count inceased20
Blood thyroid stimulating hormone increased10
SecondaryMean 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
Reported as:
Mean · score on a scale
Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score
score on a scaleARGX-113Placebo
Day 8-1.9 ± 2.75-0.7 ± 1.56
Day 15-2.8 ± 2.70-2.2 ± 2.08
Day 22-3.5 ± 2.84-2.5 ± 2.50
Day 29-4.1 ± 2.64-2.3 ± 2.72
Day 36-4.2 ± 3.30-2.1 ± 2.43
Day 43-3.8 ± 2.72-2.4 ± 2.69
Day 50-4.4 ± 3.53-2.9 ± 2.96
Day 64-3.4 ± 3.27-1.8 ± 3.55
Day 78-3.5 ± 3.50-1.8 ± 4.22
SecondaryMean 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
Reported as:
Mean · score on a scale
Mean Change From Baseline in QMG Score
score on a scaleARGX-113Placebo
Day 8-2.8 ± 3.130.0 ± 2.22
Day 15-4.0 ± 4.29-1.8 ± 3.08
Day 22-4.0 ± 4.55-1.8 ± 3.91
Day 29-4.9 ± 4.94-1.4 ± 3.72
Day 36-5.7 ± 5.97-1.9 ± 3.37
Day 43-4.6 ± 5.73-2.1 ± 4.55
Day 50-5.5 ± 5.84-2.1 ± 3.95
Day 64-4.5 ± 6.42-1.8 ± 4.59
Day 78-4.8 ± 7.67-2.1 ± 5.07
SecondaryMean 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
Reported as:
Mean · score on a scale
Mean Change From Baseline in MGC Score
score on a scaleARGX-113Placebo
Day 8-4.3 ± 5.87-1.3 ± 2.77
Day 15-5.8 ± 6.45-4.4 ± 4.56
Day 22-7.8 ± 6.92-4.0 ± 3.86
Day 29-8.7 ± 7.36-4.1 ± 5.22
Day 36-9.0 ± 8.73-4.1 ± 5.58
Day 43-8.6 ± 8.54-3.5 ± 5.97
Day 50-9.4 ± 7.92-4.2 ± 5.51
Day 64-7.2 ± 8.65-3.8 ± 6.84
Day 78-7.1 ± 9.71-3.8 ± 6.83
SecondaryMean 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
Reported as:
Mean · score on a scale
Mean Change From Baseline in MGQoL15r Score
score on a scaleARGX-113Placebo
Day 8-2.0 ± 5.77-0.8 ± 1.86
Day 15-3.7 ± 4.42-1.0 ± 2.76
Day 22-4.3 ± 4.77-1.5 ± 3.17
Day 29-4.7 ± 5.44-1.5 ± 2.91
Day 36-6.0 ± 5.78-2.1 ± 3.58
Day 43-5.3 ± 5.59-1.4 ± 3.70
Day 50-4.4 ± 4.13-1.8 ± 3.71
Day 64-3.7 ± 5.10-1.3 ± 3.68
Day 78-2.7 ± 5.44-1.5 ± 3.61
SecondaryMaximum 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
Reported as:
Mean · score on a scale
Maximum Reduction From Baseline in MG-ADL Score
score on a scaleARGX-113Placebo
Maximum Reduction From Baseline in MG-ADL Score-5.1 ± 3.32-3.7 ± 2.93
SecondaryMaximum 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
Reported as:
Mean · score on a scale
Maximum Reduction From Baseline in QMG Score
score on a scaleARGX-113Placebo
Maximum Reduction From Baseline in QMG Score-7.3 ± 6.08-4.3 ± 4.16
SecondaryMaximum 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
Reported as:
Mean · score on a scale
Maximum Reduction From Baseline in MGC Score
score on a scaleARGX-113Placebo
Maximum Reduction From Baseline in MGC Score-11.5 ± 7.61-7.7 ± 4.40
SecondaryMaximum 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
Reported as:
Mean · score on a scale
Maximum Reduction From Baseline in MGQoL15r Score
score on a scaleARGX-113Placebo
Maximum Reduction From Baseline in MGQoL15r Score-7.2 ± 5.42-3.0 ± 3.16
SecondaryPharmacokinetic (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
Reported as:
Geometric mean · nanograms/milliliter (ng/mL)
Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113
nanograms/milliliter (ng/mL)ARGX-113
Cmax - Day 1179063.7 ± 31.9
Cmax - Day 8173960.4 ± 19.5
Cmax - Day 15153257.2 ± 22.1
Cmax - Day 22162655.6 ± 26.1
Ctrough - Day 17266.2 ± 43.5
Ctrough - Day 89894.8 ± 54.7
Ctrough - Day 1510045.5 ± 56.7
Ctrough - Day 2210944.6 ± 71.1
SecondaryPK 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.
Reported as:
Median · hours
PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113
hoursARGX-113
Day 12.44 (2.08 to 2.58)
Day 82.50 (2.08 to 2.50)
Day 152.50 (2.07 to 2.50)
Day 222.46 (2.08 to 2.67)
SecondaryPK 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
Reported as:
Geometric mean · hours
PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113
hoursARGX-113
PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113116.08 ± 15.8
SecondaryPK Parameters - Accumulation Ratio (Rac) of ARGX-113

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

Time frame:
Days 1 and 22.
Reported as:
Geometric mean · ratio
PK Parameters - Accumulation Ratio (Rac) of ARGX-113
ratioARGX-113
PK Parameters - Accumulation Ratio (Rac) of ARGX-1130.9360 ± 25.7
SecondaryMean 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
Reported as:
Mean · percentage change
Mean Percent Change From Baseline in Immunoglobulins (IgGs)
percentage changeARGX-113Placebo
Total IgG - Day 22-70.0 ± 10.96-2.8 ± 15.34
Total IgG - Day 78-20.4 ± 24.966.4 ± 27.49
IgG1 - Day 22-65.5 ± 8.56-2.1 ± 9.29
IgG1 - Day 78-16.0 ± 18.17-1.1 ± 19.01
IgG2 - Day 22-61.0 ± 6.73-4.4 ± 6.99
IgG2 - Day 78-34.9 ± 16.02-5.3 ± 17.63
IgG3 - Day 22-65.25 ± 10.0450.57 ± 9.566
IgG3 - Day 78-5.19 ± 18.4222.52 ± 15.341
IgG4 - Day 22-49.48 ± 10.2780.79 ± 6.592
IgG4 - Day 784.16 ± 25.5131.57 ± 16.730
SecondaryMean 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
Reported as:
Mean · percentage change
Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies
percentage changeARGX-113Placebo
Day 22-52.2686 ± 26.32992-0.3236 ± 8.50886
Day 78-1.3361 ± 34.33867-7.8881 ± 33.43325
SecondaryNumber 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
Reported as:
Number · participants
Number of Patients With an Anti-drug Antibodies (ADA) Response
participantsARGX-113Placebo
Patients with pre-dose ADA titers42
Patients with post-dose ADA titers43

Adverse events

Collected over Day 1 to Day 78.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ARGX-1130/12 (0%)0/12 (0%)10/12 (83.3%)
Placebo0/12 (0%)0/12 (0%)10/12 (83.3%)
Most frequent other events
Showing 10 of 49
Most frequent other events
EventARGX-113Placebo
HeadacheNervous system disorders4/123/12
ToothacheGastrointestinal disorders0/122/12
Tooth abscessInfections and infestations0/122/12
ArthralgiaMusculoskeletal and connective tissue disorders0/122/12
MyalgiaMusculoskeletal and connective tissue disorders2/120/12
B-lymphocyte count decreasedInvestigations2/120/12
Lymphocyte count decreasedInvestigations2/120/12
Monocyte count decreasedInvestigations2/120/12
Neutrophil count increasedInvestigations2/120/12
PruritusSkin and subcutaneous tissue disorders1/122/12

Baseline characteristics

Baseline characteristics are summarized for the randomized population which included patients who had been allocated to a randomized treatment group, regardless of whether they received the planned treatment or not.

Age, Categorical
Age, Categorical(Participants)ARGX-113PlaceboTotal
<=18 years000
Between 18 and 65 years81018
>=65 years426
Age, Continuous
Age, Continuous(years)ARGX-113PlaceboTotal
Mean55.3 ± 13.6043.5 ± 19.2849.4 ± 17.39
Sex: Female, Male
Sex: Female, Male(Participants)ARGX-113PlaceboTotal
Female7815
Male549
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)ARGX-113PlaceboTotal
Hispanic or Latino000
Not Hispanic or Latino111223
Unknown or Not Reported101
Race (NIH/OMB)
Race (NIH/OMB)(Participants)ARGX-113PlaceboTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American011
White111122
More than one race000
Unknown or Not Reported000
Body Weight
Body Weight(kg)ARGX-113PlaceboTotal
Mean74.08 ± 15.47775.21 ± 14.34374.64 ± 14.604
08

Study locations

19 sites
  • Investigator Site 19
    Irvine, California, United States
  • Investigator Site 17
    Los Angeles, California, United States
  • Investigator Site 15
    Tampa, Florida, United States
  • Investigator Site 16
    Indianapolis, Indiana, United States
  • Investigator Site 14
    Chapel Hill, North Carolina, United States
  • Investigator Site 18
    Dublin, Ohio, United States
  • Investigator Site 2
    Gent, Belgium
  • Investigator Site 1
    Leuven, Belgium
  • Investigator Site 4
    Montréal, Canada
  • Investigator Site 3
    Toronto, Canada
  • Investigator Site 7
    Bergamo, Italy
  • Investigator Site 6
    Milano, Italy
  • Investigator Site 5
    Roma, Italy
  • Investigator Site 8
    Leiden, Netherlands
  • Investigator Site 10
    Gdańsk, Poland
  • Investigator Site 9
    Kraków, Poland
  • Investigator Site 12
    Barcelona, Spain
  • Investigator Site 11
    Madrid, Spain
  • Investigator Site 13
    Solna, Sweden
09

References and documents

Study documents

  • Study protocol · Nov 28, 2016
  • Statistical analysis plan · Oct 6, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 28, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02965573
Lead sponsor
argenx
Collaborators
Quintiles, Inc.
Responsible party
Sponsor
First posted
Nov 17, 2016
Start date
Dec 30, 2016
Primary completion
Oct 20, 2017
Completion
Oct 20, 2017
Results posted
Jan 8, 2021
Last update
Aug 28, 2024

Study contacts

Antonio Guglietta, MD
study director · argenx

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Myasthenia Gravis→

Other studies from this sponsor

argenx

Start the discussion