Clinical trial NCT04833894: Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in Children with Generalized Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Generalized Myasthenia Gravis
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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)


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.

Primary outcomes:
measure: Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Clearance (CL)
timeFrame: up to 26 weeks
measure: Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Volume of Distribution (Vd)
timeFrame: up to 26 weeks
measure: Total Immunoglobulin G (IgG) levels as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis
timeFrame: up to 26 weeks
measure: Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis
timeFrame: up to 26 weeks
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
timeFrame: up to 28 weeks
measure: Efgartigimod serum concentrations from blood samples
timeFrame: up to 26 weeks
measure: Absolute values of levels of total Immunoglobulin G (IgG) from blood samples
timeFrame: up to 26 weeks
measure: Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples
timeFrame: up to 26 weeks
measure: Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples
timeFrame: up to 26 weeks
measure: Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples
timeFrame: up to 26 weeks
measure: Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples
timeFrame: up to 26 weeks
measure: Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples
timeFrame: up to 26 weeks
measure: Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples
timeFrame: up to 28 weeks
measure: Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples
timeFrame: up to 28 weeks
measure: 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.
timeFrame: up to 26 weeks
measure: 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.
timeFrame: up to 26 weeks
measure: Absolute values of total Quantitative Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.
timeFrame: up to 26 weeks
measure: Change from baseline of total Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.
timeFrame: up to 26 weeks
measure: Absolute values of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)
timeFrame: up to 26 weeks
measure: Change from baseline of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)
timeFrame: up to 26 weeks
measure: Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire
timeFrame: up to 26 weeks
measure: Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire
timeFrame: up to 26 weeks
measure: Change in protective antibody titers to vaccines received before or during the trial from blood samples
timeFrame: up to 28 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital of Chicago - Main Hospital
state: Illinois
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlottesville
country: United States
facility: University of Virginia (UVA) Health - Developmental Pediatrics Clinic
state: Virginia
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Antwerpen
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Marseille
country: France
facility: AP-HM - Hopital de la Timone
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris (AP-HP) - Hopital Necker-Enfants Malades
city: Tbilisi
country: Georgia
facility: Vian - M. Iashvili Children's Central Hospital
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University - Givi Zhvania Pediatric Academic Clinic
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum - Sozialpadiatrisches Zentrum
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Consorziale Di Bari
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria A. Meyer
city: Genova
country: Italy
facility: Ospedale Giannina Gaslini
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Woj. Pomorskie
city: Katowice
country: Poland
facility: Wielospecjalistyczna Poradnia Lekarska Synapsis
state: Woj. Slaskie
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny - Uniwersyteckie Centrum Kliniczne WUM
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: London
country: United Kingdom
facility: Great Ormand Street Hospital for Children NHS Foundation Trust - Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust - Royal Manchester Children's Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust - John Radcliffe Hospital Children's Hospital
Study officials:
References: