A Phase 3 Study to Evaluate the Efficacy and Safety of Efgartigimod IV in Patients With Acetylcholine Receptor Binding Antibody Seronegative Generalized Myasthenia Gravis

Phase 3Active Not RecruitingNCT06298552

argenx119 enrolled

Overview

The primary purpose of this study is to measure the efficacy and safety of efgartigimod IV compared to placebo in participants with Acetylcholine Receptor Binding Antibody (AChR-Ab) seronegative Generalized Myasthenia Gravis (gMG). The study consists of a Part A where participants will be randomized to receive either efgartigimod IV or placebo IV and a Part B where participants completing part A will receive open-label efgartigimod IV. Participants will be in the study for up to (approximately) 3.5 years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

119

Conditions

Generalized Myasthenia Gravis gMG Myasthenia Gravis, Generalized Myasthenia Gravis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * The participant is at least 18 years of age and the local legal age of consent for clinical studies when signing the ICF. * The participant is capable of providing signed informed consent and following with protocol requirements. * The participant agrees to use contraceptive measures consistent with local regulations and the women of child-bearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline before receiving the study drug. * The participant has no known weakness in infancy and later develop fatigable weakness after aged 16 years and diagnosed with acquired gMG of both of the following: 1. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation (RNS) or is for anti-muscle-specific kinase antibodies (MuSK-Ab) seropositive 2. Either a history of positive edrophonium chloride test OR a demonstrated improvement in MG signs with treatments such as oral acetylcholinesterase (AChE) inhibitors, plasma exchange (PLEX), immunoabsorption, or intravenous immunoglobulin (IVIg)/ subcutaneous immunoglobulin (SCIg) treatment * The participant is receiving a stable dose of MG therapy before screening, including acetylcholinesterase (AChE) inhibitors, steroids, or nonsteroidal immunosuppressive therapies (NSISTs) in combination or alone Exclusion Criteria: * Known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of gMG or puts the participant at undue risk * History of malignancy, cancer, unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years. Adequately treated participants with the following cancers can be included at any time: 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 * Clinically significant active infection that is not sufficiently resolved in the investigator's opinion or positive serum test at screening for active infection with any of the following: Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV * History of or current alcohol, drug, or medication abuse as assessed by the investigator * Pregnant or lactating state or intention to become pregnant during the study * Live or live-attenuated vaccine received \<4 weeks before screening * Worsening muscle weakness secondary to concurrent infections or medications * Received a thymectomy less than 3 months before screening or thymectomy is planned during the study The complete list of exclusion criteria can be found in the protocol.

Outcomes

Primary Outcomes

MG-ADL Total Score Change From Baseline

Time frame: Up to 29 days in part A

Secondary Outcomes

QMG Total Score Change From Baseline

The Quantitative Myasthenia Gravis (QMG) score includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no symptoms) to 39 (highest disease severity).

Time frame: Up to 29 days in part A

Proportion of Participants Who Are Both MG-ADL and QMG Responders in Part A

A participant was an MG-ADL responder if there was a ≥2-point reduction in the MG-ADL total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A. A participant was a QMG responder if there was a ≥3-point reduction in the QMG total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A.

Time frame: Up to 8 weeks (part A)

Proportion of Participants With MSE

Minimal symptom expression (MSE) is defined as an MG-ADL total score of 0 or 1

Time frame: Up to 8 weeks (part A) + 3 years (part B)

Proportion of Participants Who Are MG-ADL Responders in Part A

The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). A participant was an MG-ADL responder if there was a ≥2-point reduction in the MG-ADL total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A.

Time frame: Up to 8 weeks (part A)

Proportion of Participants Who Are QMG Responders in Part A

The Quantitative myasthenia gravis (QMG) includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no symptoms) to 39 (highest disease severity). A participant was a QMG responder if there was a ≥3-point reduction in the QMG total score compared with baseline that was maintained for at least 4 consecutive weeks (ie, at least 5 consecutive visits total), with the first reduction occurring no later than 1 week after the last administration of IMP in part A.

Time frame: Up to 8 weeks (part A)

Proportion of Participants Who Are Early MG-ADL Responders in Part A

The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (no symptoms) to 24 (most severe symptoms). An Early MG-ADL responder is an MG-ADL responder who had an onset of an MG-ADL response no later than 2 weeks after the first administration of IMP in part A.

Time frame: Up to 8 weeks (part A)

MG-ADL Total Score Change From Baseline Over Time in Part A and Part A+B

Time frame: Up to 8 weeks (part A) + 3 years (part B)

MG-QoL15r Change From Baseline Over Time in Part A and Part A+B

The Myasthenia Gravis Quality of Life-15 revised (MG-QoL15r) is a patient-reported instrument that measures the impact of MG symptoms on quality of life. The total scores range from 0 (best outcome) to 30 (worst outcome).

Time frame: Up to 8 weeks (part A) + 3 years (part B)

EQ-5D-5L VAS Change From Baseline Over Time in Part A and Part A+B

The EQ-5D-5L is a participant-reported measure of health status developed by the EuroQol Group. The questionnaire comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Current health status is rated on vertical visual analog score (VAS) from 0 to 100, with a score of 0 corresponding to "the worst health you can imagine" and 100 corresponding to "the best health you can imagine."

Time frame: Up to 8 weeks (part A) + 3 years (part B)

Total IgG Concentrations Percent Changes From Baseline Over Time in Part A and Part A+B

Time frame: Up to 8 weeks (part A) + 3 years (part B)

A Phase 3 Study to Evaluate the Efficacy and Safety of Efgartigimod IV in Patients With Acetylcholine Receptor Binding Antibody Seronegative Generalized Myasthenia Gravis

Overview

Conditions

Interventions

Eligibility

Locations (91)

Outcomes

Primary Outcomes

Secondary Outcomes