Generalized Myasthenia Gravis
Conditions
Brief summary
The purpose of this study is to investigate the Pharmacodynamics (PD), Pharmacokinetics (PK), safety, tolerability, immunogenicity, and clinical efficacy of efgartigimod coformulated with recombinant human hyaluronidase PH20 (rHuPH20) as compared to efgartigimod IV infused in patients with generalized myasthenia gravis (gMG). The study duration is approximately 12 weeks. After screening, patients will be randomized to receive either efgartigimod infusions or efgartigimod PH20 subcutaneously (SC)
Detailed description
Main objective of the trial: To demonstrate that the pharmacodynamic (PD) effect of injections of 1000 mg efgartigimod PH20 SC (efgartigimod co-formulated with recombinant humanhyaluronidase PH20 for subcutaneous administration), administered once weekly for 4 administrations, is NI (noninferior) to IV infusions of efgartigimod (efgartigimod formulation for intravenous infusion) at a dose of 10 mg/kg administered once weekly for 4 administrations. Secondary objectives: To compare the PD effect of efgartigimod PH20 SC and efgartigimod IV over time; To evaluate the pharmacokinetics (PK) of efgartigimod PH20 SC and efgartigimod IV; To evaluate the safety, tolerability, and immunogenicity of efgartigimod PH20 SC and efgartigimod IV; To evaluate the clinical efficacy of efgartigimod PH20 SC and efgartigimod IV.
Interventions
BIOLOGICALefgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC
BIOLOGICALefgartigimod IV
Intravenous infusion of efgartigimod
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Bullet list of each inclusion criterium: 1. Must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. At least 18 years of age at the time of signing the informed consent form. 3. Diagnosed with generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by at least 1 of the following: 1. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation 2. History of positive edrophonium chloride test 3. Demonstrated improvement in Myasthenia Gravis (MG) signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician 4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa, or IVb
Exclusion criteria
Bullet list of each exclusion criterium: 1. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of Investigational Medicinal Product. 2. Has any of the following medical conditions: 1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening 2. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of myasthenia gravis or put the participant at undue risk. 3. History of malignancy unless deemed cured by adequate treatment with no evidence of reoccurrence for ≥3 years before the first administration of the IMP. Participants with the following cancers can be included at any time: * adequately treated basal cell or squamous cell skin cancer * carcinoma in situ of the cervix * carcinoma in situ of the breast * incidental histological findings of prostate cancer (TNM Classification of Malignant Tumors stage T1a or T1b). 4. Clinical evidence of other significant serious diseases, or the participant has had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set) | From week 0 to week 4 | ANCOVA Analysis of Percent Change From Baseline in Total IgG Level at Day 29 (ie, 7 days after the fourth IV or SC administration). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | From baseline to week 10 | Percent reduction from baseline in AChR-Ab levels over time in AChR-Ab positive patients measured in mITT Analysis Set. Descriptive statistics have been used for this secondary end point. |
| Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Baseline to week 10 | Median (IQR) Percent Change From Baseline for the IgG Subtypes (IgG1, IgG2, IgG3, and IgG4) in the Overall Population. The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point. |
| AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | From baseline to week 10 | AUEC of the percent reduction from baseline total IgG per dosing interval (days 1-8, days 8-15, days 15-22, and days 22-29), days 1-29, days 1-57 and over the entire study (days 1-71). The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point. |
| Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | From Week 1 to Week 4. | Evaluation of observed predose concentration (Ctrough) (after all doses for the IV and SC treatment arms). The analysis will present data from Week 1 to Week 4. Descriptive statistics have been used for this secondary end point. |
| Efgartigimod IV Serum Pharmacokinetic Parameter Cmax | From Baseline to Week 3 | Evaluation of maximum observed concentration (Cmax) (after all doses for the IV treatment arm). The analysis will present data from Baseline to Week 3. Descriptive statistics have been used for this secondary end point. |
| Incidence of ADA Against Efgartigimod (Safety Analysis Set) | From baseline to week 10 | Incidence of antidrug antibodies (ADA) against Efgartigimod in the overall population. ADA analysis is performed with a validated ELISA in a 3-tiered approach (ADA screening analysis, confirmatory analysis and a titration assay). Descriptive statistics have been used for this secondary end point. |
| Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | From baseline to week 10 | Total IgG level percent change from baseline over time for the overall population. |
| Incidence and Severity of AEs and SAEs (Safety Analysis Set) | From baseline to week 10 | Evaluation of incidence and severity of treatment-emergent adverse events (TEAEs) and incidence of serious AEs (SAEs). Descriptive statistics have been used for this secondary end point. |
| MG-ADL Responders (ITT Analysis Set) | From baseline to week 10 | Evaluation of number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders in the overall population. The MG-ADL is an 8-item patient-reported scale that assesses MG symptoms and their effects on daily activities. It evaluates a participant's capacity to perform different activities in their daily life, including talking, chewing, swallowing, breathing, brushing their teeth, combing their hair, or getting up from a chair. The MG-ADL also assesses double vision and eyelid droop. It is a discrete quantitative variable in which the 8 items are rated by the participant on a scale of 0 to 3. The total score can range from 0 to 24, with higher total scores indicating more impairment. A participant was considered a MG-ADL responder if he/she showed a reduction of at least 2 points from baseline on the MG-ADL score for at least 4 consecutive weeks. Descriptive statistics have been used for this secondary end point. |
| QMG Responders (ITT Analysis Set) | From Baseline to Week 10 | Evaluation of number and percentage of Quantitative Myasthenia Gravis (QMG) responders in the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point. One subject in the EFG IV arm had no post-baseline QMG assessment and thus was excluded from the denominator. |
| Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | From baseline to week 10 | Evaluation of MG-ADL Total Score Change from baseline over time for the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point. The MG-ADL is an 8-item patient-reported scale that assesses MG symptoms and their effects on daily activities. It evaluates a participant's capacity to perform different activities in their daily life, including talking, chewing, swallowing, breathing, brushing their teeth, combing their hair, or getting up from a chair. The MG-ADL also assesses double vision and eyelid droop. It is a discrete quantitative variable in which the 8 items are rated by the participant on a scale of 0 to 3. The total score can range from 0 to 24, with higher total scores indicating more impairment. A participant was considered a MG-ADL responder if he/she showed a reduction of at least 2 points from baseline on the MG-ADL score for at least 4 consecutive weeks. |
| Change From Baseline in QMG Score Over Time (ITT Analysis Set) | From baseline to week 10 | Evaluation of QMG Total Score change from baseline over time for the overall population (ITT Analysis Set). The QMG (Quantitative Myasthenia Gravis) quantifies disease severity based on impairments of body function and structures as defined by the International Classification of Functioning, Disability and Health. The QMG consists of 13 items that assess ocular, bulbar, and limb function. Six of the 13 items are timed endurance tests measured in seconds. Each item has a possible score from 0 to 3. The total possible score is 39, where higher total scores indicate more severe impairments. It is based on qualitative testing of specific muscle groups to assess limb function. Descriptive statistics have been used for this secondary end point. A participant was considered a QMG responder if he/she showed a reduction of at least 3 points from baseline on the QMG score for at least 4 consecutive weeks. |
| Incidence of Antibodies Against rHuPH20 in the SC Treatment Arm (Safety Analysis Set) | From baseline to week 10 | Incidence of antibodies against rHuPH20 in the Efgartigimod PH20 SC Arm. antibody analysis is performed with a validated ELISA in a 3-tiered approach (screening analysis, confirmatory analysis and a titration assay) Descriptive statistics have been used for this secondary end point. |
Countries
Belgium, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russia, Spain, United States
Participant flow
Recruitment details
Participant's evaluation of eligibility was performed at screening and confirmed at randomization visit 1. The overall study duration per subject was approximately 12 weeks spanning the study periods - 2 weeks for screening, 3 weeks for treatment, and 7 weeks for follow-up.
Pre-assignment details
153 patients were screened, 111 patients were randomized 1:1 to receive efgartigimod PH20 SC 1000 mg (55) or efgartigimod IV 10 mg/kg (56) once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22). 110 patients started in the study (received treatment) as one participant randomized to the efgartigimod IV arm did not receive treatment due to an AE. 55 patients received study treatment in each treatment arm.
Participants by arm
| Arm | Count |
|---|---|
| Efgartigimod PH20 SC Patients receiving 1000 mg efgartigimod PH20 subcutaneous (SC) treatment.
efgartigimod PH20 SC: Subcutaneous injection with efgartigimod PH20 SC | 55 |
| Efgartigimod IV Patients receiving 10 mg/kg efgartigimod intravenous (IV) treatment.
efgartigimod IV: Intravenous infusion of efgartigimod | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Other - due to personal reason | 1 | 0 |
Baseline characteristics
| Characteristic | Efgartigimod PH20 SC | Efgartigimod IV | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 18 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 37 Participants | 80 Participants |
| Age, Continuous | 53.0 years | 59.0 years | 53.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 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 | 50 Participants | 51 Participants | 101 Participants |
| Sex: Female, Male Female | 31 Participants | 34 Participants | 65 Participants |
| Sex: Female, Male Male | 24 Participants | 21 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 37 / 55 | 23 / 55 |
| serious Total, serious adverse events | 8 / 55 | 4 / 55 |
Outcome results
Primary
Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set)
ANCOVA Analysis of Percent Change From Baseline in Total IgG Level at Day 29 (ie, 7 days after the fourth IV or SC administration).
Time frame: From week 0 to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set) | -66.4 percent |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set) | -62.2 percent |
Comparison: The primary endpoint was analyzed using an ANCOVA model with treatment as a factor and total IgG levels at baseline as a covariate. The NI evaluation was based on a percent reduction from baseline in total IgG levels at day 29 (week 4) using an NI margin of 10%. Only the results for mITT analysis set are entered.p-value: <0.000195% CI: [-7.73, -0.66]ANCOVA
Secondary
AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set)
AUEC of the percent reduction from baseline total IgG per dosing interval (days 1-8, days 8-15, days 15-22, and days 22-29), days 1-29, days 1-57 and over the entire study (days 1-71). The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 15-22 (week 2-week 3) | -416.0 percent days | Standard Error 12.06 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-29 (baseline-week 4) | -1332.5 percent days | Standard Error 30.78 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 8-15 (week 1-week 2) | -341.9 percent days | Standard Error 9.9 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-57 (baseline-week 8) | -2515.9 percent days | Standard Error 96.98 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 22-29 (week 3-week 4) | -447.3 percent days | Standard Error 9.24 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-71 (baseline-week 10) | -2562.9 percent days | Standard Error 171.86 |
| Efgartigimod PH20 SC | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-8 (baseline-week 1) | -138.9 percent days | Standard Error 5.48 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-71 (baseline-week 10) | -2500.3 percent days | Standard Error 116.1 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-8 (baseline-week 1) | -139.1 percent days | Standard Error 5.67 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 8-15 (week 1-week 2) | -328.3 percent days | Standard Error 10.98 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 15-22 (week 2-week 3) | -399.8 percent days | Standard Error 14.46 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 22-29 (week 3-week 4) | -427.0 percent days | Standard Error 9.76 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-29 (baseline-week 4) | -1311.6 percent days | Standard Error 26.35 |
| Efgartigimod IV | AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set) | Days 1-57 (baseline-week 8) | -2387.6 percent days | Standard Error 77.61 |
Secondary
Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set)
Evaluation of MG-ADL Total Score Change from baseline over time for the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point. The MG-ADL is an 8-item patient-reported scale that assesses MG symptoms and their effects on daily activities. It evaluates a participant's capacity to perform different activities in their daily life, including talking, chewing, swallowing, breathing, brushing their teeth, combing their hair, or getting up from a chair. The MG-ADL also assesses double vision and eyelid droop. It is a discrete quantitative variable in which the 8 items are rated by the participant on a scale of 0 to 3. The total score can range from 0 to 24, with higher total scores indicating more impairment. A participant was considered a MG-ADL responder if he/she showed a reduction of at least 2 points from baseline on the MG-ADL score for at least 4 consecutive weeks.
Time frame: From baseline to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 2 | -3.6 Total score on a scale | Standard Error 0.4 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 6 | -4.2 Total score on a scale | Standard Error 0.35 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 4 | -5.1 Total score on a scale | Standard Error 0.38 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 7 | -3.9 Total score on a scale | Standard Error 0.35 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 3 | -4.7 Total score on a scale | Standard Error 0.36 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 8 | -3.3 Total score on a scale | Standard Error 0.34 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 5 | -4.9 Total score on a scale | Standard Error 0.36 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 10 | -2.2 Total score on a scale | Standard Error 0.44 |
| Efgartigimod PH20 SC | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 1 | -2.2 Total score on a scale | Standard Error 0.33 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 10 | -2.1 Total score on a scale | Standard Error 0.43 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 1 | -2.0 Total score on a scale | Standard Error 0.3 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 2 | -3.2 Total score on a scale | Standard Error 0.35 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 3 | -4.3 Total score on a scale | Standard Error 0.33 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 4 | -4.7 Total score on a scale | Standard Error 0.37 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 5 | -4.3 Total score on a scale | Standard Error 0.41 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 6 | -3.7 Total score on a scale | Standard Error 0.44 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 7 | -3.6 Total score on a scale | Standard Error 0.44 |
| Efgartigimod IV | Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set) | Week 8 | -2.9 Total score on a scale | Standard Error 0.4 |
Secondary
Change From Baseline in QMG Score Over Time (ITT Analysis Set)
Evaluation of QMG Total Score change from baseline over time for the overall population (ITT Analysis Set). The QMG (Quantitative Myasthenia Gravis) quantifies disease severity based on impairments of body function and structures as defined by the International Classification of Functioning, Disability and Health. The QMG consists of 13 items that assess ocular, bulbar, and limb function. Six of the 13 items are timed endurance tests measured in seconds. Each item has a possible score from 0 to 3. The total possible score is 39, where higher total scores indicate more severe impairments. It is based on qualitative testing of specific muscle groups to assess limb function. Descriptive statistics have been used for this secondary end point. A participant was considered a QMG responder if he/she showed a reduction of at least 3 points from baseline on the QMG score for at least 4 consecutive weeks.
Time frame: From baseline to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 2 | -4.3 Total score | Standard Error 0.58 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 6 | -5.2 Total score | Standard Error 0.6 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 4 | -6.1 Total score | Standard Error 0.62 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 7 | -3.9 Total score | Standard Error 0.61 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 3 | -5.7 Total score | Standard Error 0.61 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 8 | -3.7 Total score | Standard Error 0.66 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 5 | -5.9 Total score | Standard Error 0.61 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 10 | -2.3 Total score | Standard Error 0.6 |
| Efgartigimod PH20 SC | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 1 | -3 Total score | Standard Error 0.48 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 10 | -2.8 Total score | Standard Error 0.53 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 1 | -2 Total score | Standard Error 0.44 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 2 | -3.4 Total score | Standard Error 0.44 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 3 | -4.5 Total score | Standard Error 0.5 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 4 | -5.2 Total score | Standard Error 0.52 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 5 | -5 Total score | Standard Error 0.57 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 6 | -5 Total score | Standard Error 0.61 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 7 | -4.1 Total score | Standard Error 0.55 |
| Efgartigimod IV | Change From Baseline in QMG Score Over Time (ITT Analysis Set) | Week 8 | -3.3 Total score | Standard Error 0.53 |
Secondary
Efgartigimod IV Serum Pharmacokinetic Parameter Cmax
Evaluation of maximum observed concentration (Cmax) (after all doses for the IV treatment arm). The analysis will present data from Baseline to Week 3. Descriptive statistics have been used for this secondary end point.
Time frame: From Baseline to Week 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Efgartigimod IV Serum Pharmacokinetic Parameter Cmax | Cmax Baseline | 199 μg/mL | Standard Deviation 62.8 |
| Efgartigimod PH20 SC | Efgartigimod IV Serum Pharmacokinetic Parameter Cmax | Cmax week 1 | 215 μg/mL | Standard Deviation 63 |
| Efgartigimod PH20 SC | Efgartigimod IV Serum Pharmacokinetic Parameter Cmax | Cmax week 2 | 211 μg/mL | Standard Deviation 75 |
| Efgartigimod PH20 SC | Efgartigimod IV Serum Pharmacokinetic Parameter Cmax | Cmax week 3 | 206 μg/mL | Standard Deviation 59.5 |
Secondary
Incidence and Severity of AEs and SAEs (Safety Analysis Set)
Evaluation of incidence and severity of treatment-emergent adverse events (TEAEs) and incidence of serious AEs (SAEs). Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE | 67.3 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 SAE | 14.5 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Grade 3 or higher AE | 16.4 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AESI | 18.2 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Injection site reaction (localized) | 38.2 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Infusion- or injection-related reaction | 25.5 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Fatal AE | 0 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Treatment-related AE according to PI | 43.6 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Procedure-related AE according to PI | 25.5 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Treatment-related SAE | 0 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE for which the IMP was interrupted | 1.8 Percent of patients |
| Efgartigimod PH20 SC | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE for which the IMP was discontinued | 3.6 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE for which the IMP was interrupted | 0 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE | 50.9 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Fatal AE | 0 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 SAE | 7.3 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Treatment-related SAE | 0 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Grade 3 or higher AE | 7.3 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Treatment-related AE according to PI | 21.8 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AESI | 16.4 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 AE for which the IMP was discontinued | 0 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Injection site reaction (localized) | 1.8 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Procedure-related AE according to PI | 3.6 Percent of patients |
| Efgartigimod IV | Incidence and Severity of AEs and SAEs (Safety Analysis Set) | ≥1 Infusion- or injection-related reaction | 3.6 Percent of patients |
Secondary
Incidence of ADA Against Efgartigimod (Safety Analysis Set)
Incidence of antidrug antibodies (ADA) against Efgartigimod in the overall population. ADA analysis is performed with a validated ELISA in a 3-tiered approach (ADA screening analysis, confirmatory analysis and a titration assay). Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Incidence of ADA Against Efgartigimod (Safety Analysis Set) | 34.5 Percent of patients |
| Efgartigimod IV | Incidence of ADA Against Efgartigimod (Safety Analysis Set) | 20.0 Percent of patients |
Secondary
Incidence of Antibodies Against rHuPH20 in the SC Treatment Arm (Safety Analysis Set)
Incidence of antibodies against rHuPH20 in the Efgartigimod PH20 SC Arm. antibody analysis is performed with a validated ELISA in a 3-tiered approach (screening analysis, confirmatory analysis and a titration assay) Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Incidence of Antibodies Against rHuPH20 in the SC Treatment Arm (Safety Analysis Set) | 5.5 Percent of patients |
Secondary
MG-ADL Responders (ITT Analysis Set)
Evaluation of number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders in the overall population. The MG-ADL is an 8-item patient-reported scale that assesses MG symptoms and their effects on daily activities. It evaluates a participant's capacity to perform different activities in their daily life, including talking, chewing, swallowing, breathing, brushing their teeth, combing their hair, or getting up from a chair. The MG-ADL also assesses double vision and eyelid droop. It is a discrete quantitative variable in which the 8 items are rated by the participant on a scale of 0 to 3. The total score can range from 0 to 24, with higher total scores indicating more impairment. A participant was considered a MG-ADL responder if he/she showed a reduction of at least 2 points from baseline on the MG-ADL score for at least 4 consecutive weeks. Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | MG-ADL Responders (ITT Analysis Set) | 69.1 percent |
| Efgartigimod IV | MG-ADL Responders (ITT Analysis Set) | 69.1 percent |
Secondary
Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set)
Percent reduction from baseline in AChR-Ab levels over time in AChR-Ab positive patients measured in mITT Analysis Set. Descriptive statistics have been used for this secondary end point.
Time frame: From baseline to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 10 | 13.5 percent | Standard Error 23.16 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 1 | -42.5 percent | Standard Error 1.5 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 2 | -57.4 percent | Standard Error 1.39 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 3 | -61.8 percent | Standard Error 1.6 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 4 | -62.2 percent | Standard Error 1.76 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 5 | -55.3 percent | Standard Error 1.52 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 6 | -40.4 percent | Standard Error 3.13 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 7 | -26.7 percent | Standard Error 4.76 |
| Efgartigimod PH20 SC | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 8 | -14.5 percent | Standard Error 7.82 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 7 | -15.8 percent | Standard Error 5.63 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 5 | -47.2 percent | Standard Error 2.98 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 1 | -43.7 percent | Standard Error 1.55 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 10 | 10.3 percent | Standard Error 7.85 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 2 | -55.1 percent | Standard Error 1.52 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 6 | -29.9 percent | Standard Error 4.61 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 3 | -59.2 percent | Standard Error 1.66 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 8 | -7.1 percent | Standard Error 6.02 |
| Efgartigimod IV | Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set) | Week 4 | -59.6 percent | Standard Error 1.74 |
Secondary
Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set)
Median (IQR) Percent Change From Baseline for the IgG Subtypes (IgG1, IgG2, IgG3, and IgG4) in the Overall Population. The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point.
Time frame: Baseline to week 10
Population: mITT Analysis Set: All randomized participants with a value for total IgG levels at baseline and at least 1 postbaseline timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Efgartigimod PH20 SC | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG1 | -71 Percent change |
| Efgartigimod PH20 SC | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG2 | -65.6 Percent change |
| Efgartigimod PH20 SC | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG3 | -69.6 Percent change |
| Efgartigimod PH20 SC | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG4 | -56.4 Percent change |
| Efgartigimod IV | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG4 | -55.5 Percent change |
| Efgartigimod IV | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG1 | -68.4 Percent change |
| Efgartigimod IV | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG3 | -64.7 Percent change |
| Efgartigimod IV | Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set) | Percent change from baseline at week 4 IgG2 | -64.5 Percent change |
Secondary
Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set)
Total IgG level percent change from baseline over time for the overall population.
Time frame: From baseline to week 10
Population: mITT Analysis Set: All randomized participants with a value for total IgG levels at baseline and at least 1 postbaseline timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 2 | -56.9 percent | Standard Error 1.57 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 6 | -44 percent | Standard Error 2.52 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 4 | -64.7 percent | Standard Error 1.95 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 7 | -31.2 percent | Standard Error 4.67 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 3 | -62.2 percent | Standard Error 1.41 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 8 | -8.9 percent | Standard Error 8.65 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 5 | -57.4 percent | Standard Error 1.7 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 10 | 7.8 percent | Standard Error 7.78 |
| Efgartigimod PH20 SC | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 1 | -40.1 percent | Standard Error 1.45 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 10 | -3.1 percent | Standard Error 3.82 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 1 | -39.6 percent | Standard Error 1.51 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 2 | -55.1 percent | Standard Error 1.85 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 3 | -59 percent | Standard Error 2 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 4 | -62.3 percent | Standard Error 1.24 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 5 | -49.9 percent | Standard Error 2.17 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 6 | -38.9 percent | Standard Error 2.24 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 7 | -25.3 percent | Standard Error 2.78 |
| Efgartigimod IV | Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set) | Week 8 | -14.6 percent | Standard Error 3.13 |
Secondary
QMG Responders (ITT Analysis Set)
Evaluation of number and percentage of Quantitative Myasthenia Gravis (QMG) responders in the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point. One subject in the EFG IV arm had no post-baseline QMG assessment and thus was excluded from the denominator.
Time frame: From Baseline to Week 10
Population: One patient from Efgartigimod IV didn't have any post-baseline QMG assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | QMG Responders (ITT Analysis Set) | 65.5 percent |
| Efgartigimod IV | QMG Responders (ITT Analysis Set) | 51.9 percent |
Secondary
Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough
Evaluation of observed predose concentration (Ctrough) (after all doses for the IV and SC treatment arms). The analysis will present data from Week 1 to Week 4. Descriptive statistics have been used for this secondary end point.
Time frame: From Week 1 to Week 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 1 | 18.3 μg/mL | Standard Deviation 8.05 |
| Efgartigimod PH20 SC | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 2 | 21.4 μg/mL | Standard Deviation 8.36 |
| Efgartigimod PH20 SC | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 3 | 22.5 μg/mL | Standard Deviation 9.61 |
| Efgartigimod PH20 SC | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 4 | 22.0 μg/mL | Standard Deviation 8.12 |
| Efgartigimod IV | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 4 | 14.9 μg/mL | Standard Deviation 6.43 |
| Efgartigimod IV | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 1 | 16.4 μg/mL | Standard Deviation 33 |
| Efgartigimod IV | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 3 | 15.2 μg/mL | Standard Deviation 8.05 |
| Efgartigimod IV | Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough | Ctrough week 2 | 14.0 μg/mL | Standard Deviation 6.92 |