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

A Randomized, Double-Blinded, Placebo-Controlled, Phase 3, Parallel-Group Design Study Evaluating the Efficacy and Safety of Efgartigimod IV in Adult Participants With Acetylcholine Receptor Binding Antibody Seronegative Generalized Myasthenia Gravis

The primary purpose of this study is to measure the efficacy and safety of efgartigimod intravenously (IV) compared to placebo in participants with Acetylcholine Receptor Binding Antibody (AChR-Ab) seronegative Generalized Myasthenia Gravis (gMG). Other objectives are to assess long-term efficacy, safety, and tolerability of efgartigimod.

Study will consist of:

• Screening
• Part A: participants will be randomized to receive either efgartigimod IV or placebo
• Part B: participants completing part A will receive open-label efgartigimod IV

Study Overview

• Status: Recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: Efgartigimod IV; Other: Placebo IV

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Study Locations

• United States
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Recruiting
      • First Choice Neurology Boca Raton
      • Contact: Brian Costell, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant is at least 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 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

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
• Current participation in another interventional clinical study or previous participation in an efgartigimod clinical study and received at least 1 dose of the study drug
• Known hypersensitivity to study drug or one of its excipients (inactive ingredients)
• 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
• Use of some medications before screening (more information is found in the protocol).

The complete list of exclusion criteria can be found in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efgartigimod IV; Patients receiving efgartigimod IV in both part A and part B	Biological: Efgartigimod IV; Intravenous infusion of efgartigimod
Placebo Comparator: Placebo; Patients receiving placebo during part A and receiving efgartigimod IV during part B	Biological: Efgartigimod IV; Intravenous infusion of efgartigimod; Other: Placebo IV; Intravenous infusion of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myasthenia Gravis Activities of Daily Living (MG-ADL) total score change from baseline	Minimum value: 0 (normal symptoms); Maximum value: 24 (most severe symptoms)	Up to 29 days during part A

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who are both MG-ADL and QMG responders		Up to 8 weeks during part A
Quantitative myasthenia gravis (QMG) total score change from baseline	Minimum value: 0 (no disease severity); Maximum value: 39 (highest disease severity)	Up to 29 days during part A

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): July 25, 2025
• Study Completion (Estimated): July 23, 2027

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: ARGX-113-2308; 2024-511796-15-00 (Other Identifier: CTIS number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No