Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in 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

The purpose of this trial is to investigate the PK, PD, safety, and activity of efgartigimod IV in children and adolescents aged from 2 to less than 18 years of age with gMG.

Trial details include:

• The maximum trial duration for each individual participant will be approximately 28 weeks
• The treatment duration will be 8 weeks for the dose-confirmatory part (Part A) and 18 weeks for the treatment response-confirmatory part (Part B)

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

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

Study Locations

• Austria
  • Wien, Austria, 1090
    • Withdrawn
    • Medizinische Universität Wien
• Belgium
  • Antwerpen, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
    • Contact: Diane Beysen, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Canada
  • Vancouver, Canada, V6H 3V4
    • Not yet recruiting
    • British Columbia Children's Hospital
    • Contact: Kathryn Selby, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
• France
  • Marseille, France, 13004
    • Not yet recruiting
    • Hopitaux de La Timone
    • Contact: Brigitte Chabrol, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
  • Paris, France, 75015
    • Not yet recruiting
    • Groupe Hospitalier Necker Enfants Malades
    • Contact: Isabelle Desguerre, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Georgia
  • Tbilisi, Georgia, 0177
    • Recruiting
    • JSC Evex Hospitals
    • Contact: Nino Tatishvili, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Tbilisi, Georgia, 0186
    • Not yet recruiting
    • LEPL ''Tblisi State Medical University Givi Zhvani
    • Contact: Sophia Bakhtadze, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
• Germany
  • Berlin, Germany, 13353
    • Not yet recruiting
    • Charite - Universitatsmedizin Berlin
    • Contact: Corinna Stoltenburg, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Essen, Germany, 45147
    • Not yet recruiting
    • Universitätsklinikum Essen
    • Contact: Adela Della Marina, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Italy
  • Bari, Italy, 70120
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Consorziale Policlinico Di Bari
    • Contact: Emilia Matera, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Florence, Italy, 50139
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria A. Meyer
    • Contact: Renzo Guerrini, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
  • Genova, Italy, 16147
    • Not yet recruiting
    • Istituto G Gaslini Ospedale Pediatrico IRCCS
    • Contact: Chiara Fiorillo, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Netherlands
  • Leiden, Netherlands, 2333
    • Recruiting
    • Leiden University Medical Center
    • Contact: Erik Harmen Niks, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Poland
  • Warszawa, Poland, 02-097
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny
    • Contact: Anna Kostera-Pruszczyk, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
  • Woj. Pomorskie
    • Gdańsk, Woj. Pomorskie, Poland, 80-952
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne
      • Contact: Maria Mazurkiewicz-Beldzinska, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
  • Woj. Slaskie
    • Katowice, Woj. Slaskie, Poland, 40-123
      • Recruiting
      • Wielospecjalistyczna Poradnia Lekarska Synapsis
      • Contact: Marek Smilowski, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• Spain
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe de Valencia
    • Contact: Teresa Sevilla Mantecón, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Cataluña
    • Barcelona, Cataluña, Spain, 08950
      • Not yet recruiting
      • Hospital Sant Joan de Deu
      • Contact: Andres Nascimento, MD; Phone Number: 8573504834; Email: clinicaltrials@argenx.com
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Recruiting
    • Great Ormond Street Hospital for Children
    • Contact: Pinki Munot, MD; Phone Number: 857-350-4834; Email: Clinicaltrials@argenx.com
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Royal Manchester Children's Hospital
    • Contact: Mary Imelda Hughes, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Oxford, United Kingdom, OX3 9DU
    • Recruiting
    • Oxford University hospitals NHS Foundation Trust-Oxford Children's Hospital
    • Contact: Sithara Ramdas, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann and Robert H Lurie Childrens Hospital of Chicago
      • Contact: Nancy Kuntz, MD; Phone Number: 857-350-4834; Email: Clinicaltrials@argenx.com
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • University of North Carolina at Chapel Hill
      • Contact: James Howard, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Anna Jesus, MD; Phone Number: 857-350-4834; Email: Clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

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; Patients receiving efgartigimod intravenous (IV) treatment	Biological: Efgartigimod IV; Intravenous infusion of Efgartigimod

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Clearance (CL)	Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod	up to 26 weeks
Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Volume of Distribution (Vd)	Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod	up to 26 weeks
Total Immunoglobulin G (IgG) levels as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis	Total Immunoglobulin G levels will be measured from blood samples	up to 26 weeks
Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis	Total Immunoglobulin G (IgG) levels will be measured from blood samples	up to 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)		up to 28 weeks
Efgartigimod serum concentrations from blood samples		up to 26 weeks
Absolute values of levels of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		up to 28 weeks
Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		up to 28 weeks
Absolute values of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score. Total score can range from 0 to 24, with higher total scores indicating more impairment.		up to 26 weeks
Change from baseline of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score. Total score can range from 0 to 24, with higher total scores indicating more impairment.		up to 26 weeks
Absolute values of total Quantitative Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.		up to 26 weeks
Change from baseline of total Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.		up to 26 weeks
Absolute values of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)	Description of the participant's health state is done by digits for 5 dimensions combined in a 5-digit number. A unique health state is defined by combining 1 level from each of the 5 dimensions. Each state is referred to in terms of a 5-digit code, whereas code 11111 would indicate no problems in any of the 5 dimensions and 33333 would indicate worst problems in any of the 5 dimensions.	up to 26 weeks
Change from baseline of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)	Description of the participant's health state is done by digits for 5 dimensions combined in a 5-digit number. A unique health state is defined by combining 1 level from each of the 5 dimensions. Each state is referred to in terms of a 5-digit code, whereas code 11111 would indicate no problems and 33333 would indicate worst problems in any of the 5 dimensions.	up to 26 weeks
Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire		up to 26 weeks
Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire		up to 26 weeks
Change in protective antibody titers to vaccines received before or during the trial from blood samples		up to 28 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 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-113-2006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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