Generalized Myasthenia Gravis
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety and tolerability of efgartigimod PH20 SC 1000 mg, and the clinical efficacy, PD, pharmacokinetics (PK), immunogenicity, impact on the quality of life (QoL) of the participants, treatment satisfaction, and administration method preference, and the feasibility of self- and caregiver-supported administration of the SC injection. Treatment duration: 3-week treatment periods, repeated as needed with at least 28 days in between treatment periods Health measurements: total levels of immunoglobulin G (IgG), Acetylcholine receptor binding autoantibodies (AChR-Ab) levels, Myasthenia Gravis Activities of Daly Living (MG-ADL).
Interventions
BIOLOGICALefgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC
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. 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. Previously participated in antecedent studies ARGX-113-2001 or ARGX-113-1705 and are eligible for roll over. 3. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: * Women of Child bearing potential (WOCBP) must have a negative urine pregnancy test at baseline before investigational medicinal product (IMP) can be administered.
Exclusion criteria
1. The participant was discontinued early from studies ARGX-113-2001 or ARGX-113-1705, unless the reason for discontinuation from study ARGX-113-1705 was to roll over into study ARGX-113-2002. a. Participants who, in the investigator's judgment, are not benefiting from efgartigimod IV in study ARGX-113-1705 Part B are not eligible for roll over into ARGX-113-2002. 2. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of investigational medicinal product (IMP) 3. Has any of the following medical conditions: 1. Clinically significant uncontrolled chronic bacterial, viral, or fungal infection at roll-over 2. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with 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 investigational medicinal product (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 4. Received a live-attenuated vaccine within 28 days prior to study entry or plan to receive a live-attenuated vaccine during the study 5. A known hypersensitivity reaction to efgartigimod, rHuPH20, or any of its excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of AEs, SAEs and AESIs | Up to 3.5 years | Adverse events, Serious Adverse event and Adverse events of special interest. Adverse events in the 'Infections and infestations' SOC were defined as AESIs because efgartigimod causes a transient reduction in total IgG levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MG-ADL Total Score Changes From Baseline | Up to week 4 of the first cycle | The Myasthenia Gravis Activities of Daily Living (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. The total score ranges from 0 to 24 with higher scores indicating more impairment. |
| Percent Change in Total IgG Levels From Baseline | Up to week 4 of the first cycle | IgG: immunoglobulin G |
| Percent Change in AChR-Ab From Baseline in AChR-Ab Seropositive Participants | Up to week 4 of the first cycle | AchR-Ab: anti-acetylcholine receptor antibodies. |
| Efgartigimod Serum Concentrations | Up to week 4 of the first cycle | — |
| Incidence of ADAs Against Efgartigimod Over Time | Up to 3.5 years | ADA: Anti-drug antibodies. |
| Incidence of NAbs Against Efgartigimod Over Time | Up to 3.5 years | NAbs: neutralizing antibodies |
| Incidence of Antibodies Against rHuPH20 Over Time | Up to 3.5 years | — |
| Incidence of NAbs Against rHuPH20 Over Time | Up to 3.5 years | NAbs: neutralizing antibodies |
| Changes in Total MG-QoL15r From Baseline | Up to week 4 of the first cycle | Myasthenia Gravis Quality of Life 15 item scale revised (MG-QoL 15r) scores range from 0 to 30 with a higher score representing more severe symptoms. |
| Changes in EQ-5D-5L VAS Score From Baseline | Up to week 4 of the first cycle | EuroQoL 5 Dimensions 5-Level (EQ-5D-5L) visual analog scale (VAS) scores range from 0 to 100 with a higher score representing better health. |
| Percent of Participants or Caregivers by Number of Training Visits Needed to be Competent to Start Self- or Caregiver-Supported Administration | Up to 3.5 years | — |
| Percent of Self- or Caregiver-supported Study Drug Administration Among All Study Treatment Visits at Home | Up to 3.5 years | — |
Countries
Belgium, Czechia, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russia, Spain, United States
Participant flow
Recruitment details
This study was conducted at 47 sites that enrolled participants in 12 countries. A total of 184 participants rolled over from ARGX-113-2001 and ARGX-113-1705, of whom 180 participants were exposed to efgartigimod PH20 SC treatment.
Pre-assignment details
All participants were adults with gMG who participated in ARGX-113-2001 or ARGX-113-1705. No randomization or blinding was performed because this was an open-label study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 41 Participants |
| Age, Categorical Between 18 and 65 years | 139 Participants |
| Age, Continuous | 50.8 years STANDARD_DEVIATION 15.5 |
| Race/Ethnicity, Customized Asian | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 172 Participants |
| Race/Ethnicity, Customized White | 161 Participants |
| Sex: Female, Male Female | 119 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 180 |
| other Total, other adverse events | 167 / 180 |
| serious Total, serious adverse events | 55 / 180 |
Outcome results
None listed