A Phase 3, Randomized, Open-Label, Parallel-Group Study to Compare the Pharmacodynamics, Pharmacokinetics, Efficacy, Safety, Tolerability, and Immunogenicity of Multiple Subcutaneous Injections of Efgartigimod PH20 SC With Multiple Intravenous Infusions of Efgartigimod in Patients With Generalized Myasthenia Gravis
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Generalized Myasthenia Gravis
- Sponsor
- argenx
- Enrollment
- 110
- Locations
- 47
- Primary Endpoint
- Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Bullet list of each inclusion criterium:
- •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.
- •At least 18 years of age at the time of signing the informed consent form.
- •Diagnosed with generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by at least 1 of the following:
- •History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation
- •History of positive edrophonium chloride test
- •Demonstrated improvement in Myasthenia Gravis (MG) signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician
- •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:
- •Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of Investigational Medicinal Product.
- •Has any of the following medical conditions:
- •Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
- •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.
- •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).
Outcomes
Primary Outcomes
Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set)
Time Frame: 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 Outcomes
- Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set)(From baseline to week 10)
- Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set)(Baseline to week 10)
- Efgartigimod IV Serum Pharmacokinetic Parameter Cmax(From Baseline to Week 3)
- Incidence of ADA Against Efgartigimod (Safety Analysis Set)(From baseline to week 10)
- Incidence of Antibodies Against rHuPH20 in the SC Treatment Arm (Safety Analysis Set)(From baseline to week 10)
- QMG Responders (ITT Analysis Set)(From Baseline to Week 10)
- Change From Baseline in QMG Score Over Time (ITT Analysis Set)(From baseline to week 10)
- Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set)(From baseline to week 10)
- MG-ADL Responders (ITT Analysis Set)(From baseline to week 10)
- AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set)(From baseline to week 10)
- Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough(From Week 1 to Week 4.)
- Incidence and Severity of AEs and SAEs (Safety Analysis Set)(From baseline to week 10)
- Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set)(From baseline to week 10)