Evaluating a new treatment for children with generalized myasthenia gravis

Open-label Uncontrolled Trial to Evaluate Pharmacokinetics, Pharmacodynamics, Safety, and Activity of Efgartigimod in Children From 2 to Less Than 18 Years of Age With Generalized Myasthenia Gravis

This study is testing a new intravenous treatment for children and teens with generalized myasthenia gravis to see if it is safe and effective.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 2 Years to 18 Years
• Sex: All
• Sponsor: argenx (Industry-sponsored)
• Locations: 25 sites (Chicago, Illinois and 24 other locations)
• Trial ID: NCT04833894 on ClinicalTrials.gov

What this trial studies

This trial investigates the pharmacokinetics, pharmacodynamics, and safety of efgartigimod administered intravenously in children and adolescents aged 2 to less than 18 years with generalized myasthenia gravis (gMG). The study is divided into two parts: an 8-week dose-confirmatory phase and an 18-week treatment response-confirmatory phase. Participants will be monitored for safety and treatment efficacy over a total duration of approximately 28 weeks.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents aged 2 to less than 18 years diagnosed with generalized myasthenia gravis.

Not a fit: Patients with other forms of myasthenia gravis or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of generalized myasthenia gravis in pediatric patients.

How similar studies have performed: While this approach is being explored in this specific population, similar treatments have shown promise in adult populations, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Ability of the participant and/or his/her legally authorized representative to understand the requirements of the trial and provide written informed consent/assent, if applicable (including consent/assent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including attending the required trial visits).
2. Male or female participants between 2 to less than 18 years of age at the time of providing informed consent/assent. Age groups are enrolled in a staggered fashion respectively: 6 participants in the 12 to less than 18 years of age group followed by 6 participants in the 2 to less than 12 years of age group at the time of providing informed consent/assent.
3. Diagnosed with Generalized Myasthenia Gravis (gMG) with confirmed documentation
4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, and IVa.
5. Eligible participants should have an unsatisfactory response (efficacy and/or safety) to immunosuppressants, steroids or acetylcholinesterase (AChE) inhibitors and should be on stable concomitant gMG therapy of adequate duration before screening.
6. Positive serologic test for acetylcholine receptor (anti-AChR) antibodies at screening (for younger participants (\<15kg) historical values can be used).
7. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

   1. Male participants: Male participants must agree to not donate sperm from of providing informed consent/assent until they have completed the trial.
   2. Female participants: Female adolescents of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before investigational medicinal product (IMP) can be administered.

Exclusion Criteria:

1. Participants with MGFA class I, IVb, and V.
2. Female adolescents of childbearing potential: Pregnancy or lactation, or the participant intends to become pregnant during the trial or within 90 days after the last dose of IMP.
3. Has any of the following medical conditions:

   1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening.
   2. 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.
   3. History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of 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
   4. Clinical evidence of other significant serious diseases, or have had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the trial or put the participant at undue risk
4. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc).
5. A documented lack of clinical response to plasma exchange (PLEX).
6. Received a live or live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated, subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.
7. Received a thymectomy \<3 months before screening or 1 is planned to be performed during the trial period.
8. The following results from these diagnostic assessments will be considered exclusionary:

   a. Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indicative of an acute or chronic infection; Hepatitis C virus (HCV) based on HCV antibody assay; Positive HIV serology at screening; Positive nasopharyngeal swab polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening.
9. Using the following prior or concomitant therapies: Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of IMP, Use of any monoclonal antibody within the 6 months before the first dose of IMP, Use of intravenous immunoglobulin (IVIg), administered subcutaneously or intramuscularly, or PLEX within 4 weeks before screening.
10. Total immunoglobulin (IgG) levels \<6 g/L below the lower limit of normal (LLN) according to the reference ranges of the central laboratory for participant by sex and age at screening.
11. A known hypersensitivity reaction to efgartigimod or any of its excipients.
12. Current participation in another interventional clinical trial or previous participation in an efgartigimod trial with at least 1 dose of IMP received.
13. History (within 12 months of screening) of current alcohol, drug, or medication abuse as assessed by the investigator.

Where this trial is running

Chicago, Illinois and 24 other locations

• Ann and Robert H Lurie Children's Hospital of Chicago - Main Hospital — Chicago, Illinois, United States (Recruiting)
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
• University of Virginia (UVA) Health - Developmental Pediatrics Clinic — Charlottesville, Virginia, United States (Recruiting)
• Medizinische Universitat Wien — Vienna, Austria (Completed)
• Universitair Ziekenhuis Antwerpen — Antwerp, Belgium (Recruiting)
• Alberta Childrens Hospital — Calgary, Canada (Recruiting)
• British Columbia Children's Hospital — Vancouver, Canada (Recruiting)
• AP-HM - Hopital de la Timone — Marseille, France (Recruiting)
• Assistance Publique Hopitaux de Paris (AP-HP) - Hopital Necker-Enfants Malades — Paris, France (Recruiting)
• Vian - M. Iashvili Children's Central Hospital — Tbilisi, Georgia (Completed)
• Tbilisi State Medical University - Givi Zhvania Pediatric Academic Clinic — Tbilisi, Georgia (Completed)
• Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum - Sozialpadiatrisches Zentrum — Berlin, Germany (Completed)
• Universitätsklinikum Essen — Essen, Germany (Completed)
• Azienda Ospedaliera Universitaria Policlinico Consorziale Di Bari — Bari, Italy (Recruiting)
• Azienda Ospedaliero Universitaria A. Meyer — Florence, Italy (Recruiting)
• Ospedale Giannina Gaslini — Genova, Italy (Recruiting)
• Leids Universitair Medisch Centrum — Leiden, Netherlands (Recruiting)
• Uniwersyteckie Centrum Kliniczne — Gdansk, Woj. Pomorskie, Poland (Recruiting)
• Wielospecjalistyczna Poradnia Lekarska Synapsis — Katowice, Woj. Slaskie, Poland (Recruiting)
• Centralny Szpital Kliniczny - Uniwersyteckie Centrum Kliniczne WUM — Warsaw, Poland (Recruiting)
• Hospital Sant Joan de Deu — Esplugues de Llobregat, Spain (Recruiting)
• Hospital Universitari i Politecnic La Fe de Valencia — Valencia, Spain (Recruiting)
• Great Ormand Street Hospital for Children NHS Foundation Trust - Great Ormond Street Hospital — London, United Kingdom (Recruiting)
• Manchester University NHS Foundation Trust - Royal Manchester Children's Hospital — Manchester, United Kingdom (Recruiting)
• Oxford University Hospitals NHS Foundation Trust - John Radcliffe Hospital Children's Hospital — Oxford, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Sabine Coppieters, MD

Conditions Generalized Myasthenia Gravis