A Study of Efgartigimod PH20 SC in Children Between 2 and Less Than 18 Years of Age With Generalized Myasthenia Gravis

An Open-label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Activity of Efgartigimod PH20 SC in Participants From 2 to Less Than 18 Years of Age With Generalized Myasthenia Gravis

The purpose of this study is to measure the pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and immunogenicity of efgartigimod PH20 SC in pediatric participants with gMG aged 2 to <18 years. The primary goal is to confirm an appropriate dose of efgartigimod PH20 SC for pediatric patients using PK and PD results from this study. Participants will receive injections of efgartigimod PH20 SC and will be monitored for safety until the end of the study. At the end of the follow-up period, eligible participants may roll over to an open-label extension (OLE) study.

Study Overview

• Status: Not yet recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: Efgartigimod PH20 SC

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant (and/or their legally authorized representative) understands the requirements of the study and is capable of providing written informed consent/assent and complying with protocol requirements
• The participant is aged 2 to <18 years at the time of informed consent/assent
• The participant has been diagnosed with generalised Myasthenia Gravis that is supported by a physical examination and confirmed seropositivity for anti-acetylcholine receptor antibodies
• The participant has had an unsatisfactory response to immunosuppressants, corticosteroids, or acetylcholinesterase inhibitors but is on stable concomitant MG therapy. If receiving corticosteroids and/or immunosuppressants, must be on a stable dose for ≥1 month before screening
• The participant agrees to use birth control consistent with local regulations and people of child-bearing potential must have a negative blood pregnancy test at screening and a negative urine pregnancy test before receiving the study drug

Exclusion Criteria:

• Is a female adolescent of child-bearing potential who is pregnant and/or lactating or intends to become pregnant during their participation in the study
• Has worsening muscle weakness secondary to a concurrent infection or as a result of a medication
• Has a documented lack of clinical response to plasma exchange (PLEX)
• Received a live or live-attenuated vaccine within <4 weeks before screening
• Received a thymectomy within 3 months before screening or is planning to get a thymectomy during their participation in the study
• Has a known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of generalised Myasthenia Gravis 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
• Has a positive PCR test for SARS-CoV-2 at screening
• Has/had a clinically significant disease, had recent major surgery (within 3 months of screening) or intends to have major surgery during the study, or has/had any other medical condition that, in the investigator's opinion, would confound the results of the study or put the participant at undue risk
• Has received a different study drug in another clinical study within <12 before screening
• Is currently participating in another interventional clinical study
• Has previously participated in an efgartigimod clinical study and received at least one dose of study drug
• Has a known hypersensitivity to study drug or any of its excipients
• Has a history of or current episode of alcohol, drug, or medication abuse as assessed by the investigator
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efgartigimod PH20 SC; Participants aged 12 to <18 years receiving efgartigimod PH20 SC treatment	Biological: Efgartigimod PH20 SC; Subcutaneous injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efgartigimod serum concentrations as input for compartmental, model-driven analysis to determine age and size dependency of Clearance (CL)	Up to 12 weeks
Efgartigimod serum concentrations as input for compartmental, model-driven analysis to determine age and size dependency of Volume Distribution (Vd)	Up to 12 weeks
Total G immunoglobulins (IgG) levels as input for pharmacokinetics (PK)/pharmacodynamics (PD) modelling analysis	Up to 12 weeks
Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK)/ pharmacodynamics (PD) modelling analysis	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)		Up to 14 weeks
Severity of adverse events (AEs)		Up to 14 weeks
Incidence of serious adverse events (SAEs)		Up to 14 weeks
Severity of serious adverse events (SAEs)		Up to 14 weeks
Incidence of adverse events of special interest (AESI)		Up to 14 weeks
Severity of adverse events of special interest (AESI)		Up to 14 weeks
Efgartigimod serum concentrations		Up to 12 weeks
Absolute values of total Immunoglobulin G (IgG) from blood samples		Up to 12 weeks
Change from baseline values of total Immunoglobulin G (IgG) from blood samples		Up to 12 weeks
Percentage change from baseline values of total Immunoglobulin G (IgG) from blood samples		Up to 12 weeks
Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		Up to 12 weeks
Change from baseline values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		Up to 12 weeks
Percentage change from baseline values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		Up to 12 weeks
Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		Up to 12 weeks
Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		Up to 12 weeks
Incidence of antibodies against rHuPH20 in serum samples		Up to 12 weeks
Prevalence of antibodies against rHuPH20 in serum samples		Up to 12 weeks
Absolute value of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score, appropriate for pediatric use	Minimum value: 0 (no impairment); Maximum value: 24 (highest impairment)	Up to 12 weeks
Change from baseline of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score, appropriate for pediatric use	Minimum value: 0 (no impairment); Maximum value: 24 (highest impairment)	Up to 12 weeks
Absolute value of Quantitative Myasthenia Gravis (QMG) score	Minimum value: 0 (no impairment); Maximum value: 39 (most severe impairment)	Up to 12 weeks
Change from baseline of Quantitative Myasthenia Gravis (QMG) score	Minimum value: 0 (no impairment); Maximum value: 39 (most severe impairment)	Up to 12 weeks
Absolute value of EuroQoL 5 Dimensions Youth (EQ-5D-Y) score		Up to 12 weeks
Change from baseline value of EuroQoL 5 Dimensions Youth (EQ-5D-Y) score		Up to 12 weeks
Change from baseline value of Neuro-QoL Pediatric Fatigue Score		Up to 12 weeks
Change from baseline value of Clinical Global Impression of Improvement (CGI-I)		Up to 12 weeks
Changes in protective antibody titers to vaccines		Up to 12 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: April 26, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 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-113-2207; 2023-506159-12-00 (Ctis)

Drug and device information, study documents

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