Generalized Myasthenia Gravis
Conditions
Brief summary
This is a Long-Term, Single-Arm, Open-Label, Multicenter Phase 3 follow-on trial of the ARGX-113-1704 study to evaluate the safety and tolerability of ARGX-113 in patients with gMG. Patients who have completed at least 1 cycle of treatment and at least 1 year of trial ARGX-113-1705 and have started Part B are eligible to enroll in the open-label trial ARGX-113-2002 to receive efgartigimod by SC administration.
Interventions
BIOLOGICALARGX-113
Intravenous administration of ARGX-113
Sponsors
argenx
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures. 2. Patients who participated in trial ARGX-113-1704 and are eligible for roll over, as specified in the protocol. Other more specific inclusion criteria are further defined in the protocol.
Exclusion criteria
1. Patients who discontinued early from trial ARGX-113-1704 or patients who discontinued early from randomized treatment for pregnancy or rescue reasons or an (S)AE that might jeopardize the safety of the patient in that trial. 2. Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing. Women or childbearing potential should have a negative urine pregnancy test at SEB. 3. Male patients who are sexually active and do not intend to use effective methods of contraception during the trial or within 90 days after the last dosing or male patients who plan to donate sperm during the trial or within 90 days after the last dosing. 4. Patients with known Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) seropositivity. Other, more specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants | TEAEs were collected from the start of first administered study treatment (Day 1) up to end of follow-up, approximately up to 3 years | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any clinically significant abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (electrocardiogram \[ECG\], radiological scans, vital signs measurements) were collected as AEs. All AEs starting on or after first dose administered and until completion of participant's last visit were considered as TEAEs. A serious AE (SAE) was any AE that resulted in death, was life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality, or was medically significant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population | TEAEs were collected from the start of first administered study treatment (Day 1) up to end of follow-up, approximately up to 3 years | Overall population included both AChR-Ab seropositive and AChR-Ab seronegative participants. An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any clinically significant abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (ECG, radiological scans, vital signs measurements) were collected as AEs. All AEs starting on or after first dose administered and until completion of participant's last visit were considered as TEAEs. An SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality, or was medically significant. |
Countries
Belgium, Canada, Czechia, Denmark, France, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russia, Serbia, United States
Participant flow
Recruitment details
This Phase III, open-label study was a follow-on study of ARGX-113-1704 (NCT03669588) and was conducted in participants with myasthenia gravis having generalized muscle weakness at 51 investigational sites in 14 countries between 01 Mar 2019 and 30 Jun 2022. This study was conducted in 2 sequential parts: Part A (1 year) and Part B (\<=2 years).
Pre-assignment details
Participants from ARGX-113-1704 who either completed that study or required retreatment that could not be completed during a treatment cycle in that study were included in this study to receive efgartigimod. A total of 151 participants rolled over to this study and 145 of them received at least 1 dose of study treatment. Participants starting part B of this study were eligible to roll over in ARGX-113-2002 study.
Participants by arm
| Arm | Count |
|---|---|
| Efgartigimod Participants were administered efgartigimod IV 10 mg/kg over 1 hour every 7 days for 4 administrations per TP for 3 weeks in this study irrespective of whether they received efgartigimod or placebo in ARGX-113-1704. After the fourth infusion, participants entered an ITP of variable duration (minimum 4 weeks between treatment periods). Subsequent TPs were implemented according to clinical response. | 145 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 5 |
| Overall Study | Other | 88 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Sponsor decision | 1 |
| Overall Study | Study terminated by Sponsor | 1 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Efgartigimod |
|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 14.76 |
| Anti-acetylcholine receptor antibodies (AChR-Ab) status AChR-Ab seronegative | 34 Participants |
| Anti-acetylcholine receptor antibodies (AChR-Ab) status AChR-Ab seropositive | 111 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants |
| Race/Ethnicity, Customized Japanese | 10 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 126 Participants |
| Race/Ethnicity, Customized White | 126 Participants |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 145 |
| other Total, other adverse events | 83 / 145 |
| serious Total, serious adverse events | 36 / 145 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any clinically significant abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (electrocardiogram \[ECG\], radiological scans, vital signs measurements) were collected as AEs. All AEs starting on or after first dose administered and until completion of participant's last visit were considered as TEAEs. A serious AE (SAE) was any AE that resulted in death, was life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality, or was medically significant.
Time frame: TEAEs were collected from the start of first administered study treatment (Day 1) up to end of follow-up, approximately up to 3 years
Population: The Safety Analysis set consisted of all participants who rolled over from ARGX-113-1704 and received \>=1 dose or part of a dose of efgartigimod in this study. Only those participants with AChR-positive status are included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efgartigimod | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants | TEAE | 92 Participants |
| Efgartigimod | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants | Treatment-emergent SAE | 28 Participants |
| Efgartigimod | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants | TEAEs leading to study drug discontinuation | 10 Participants |
| Efgartigimod | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in AChR-Positive Participants | Fatal TEAE | 4 Participants |
Secondary
Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population
Overall population included both AChR-Ab seropositive and AChR-Ab seronegative participants. An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any clinically significant abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (ECG, radiological scans, vital signs measurements) were collected as AEs. All AEs starting on or after first dose administered and until completion of participant's last visit were considered as TEAEs. An SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality, or was medically significant.
Time frame: TEAEs were collected from the start of first administered study treatment (Day 1) up to end of follow-up, approximately up to 3 years
Population: The Safety Analysis set consisted of all participants who rolled over from ARGX-113-1704 and received \>=1 dose or part of a dose of efgartigimod in this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efgartigimod | Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population | TEAE | 124 Participants |
| Efgartigimod | Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population | Treatment-emergent SAE | 36 Participants |
| Efgartigimod | Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population | TEAEs leading to study drug discontinuation | 12 Participants |
| Efgartigimod | Number of Participants With TEAEs, Treatment-Emergent SAEs, TEAEs Leading to Study Drug Discontinuation and Fatal TEAE in the Overall Population | Fatal TEAE | 5 Participants |