Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in Children With Generalized Myasthenia Gravis

Официальное название

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

Обзор

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)

Вмешательства

• Биопрепарат Efgartigimod IV
  Intravenous infusion of Efgartigimod

Первичные конечные точки

• Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Clearance (CL) [Срок оценки: up to 26 weeks]
• Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Volume of Distribution (Vd) [Срок оценки: up to 26 weeks]
• Total Immunoglobulin G (IgG) levels as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis [Срок оценки: up to 26 weeks]
• Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis [Срок оценки: up to 26 weeks]

Вторичные конечные точки (12)

• Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [Срок оценки: up to 28 weeks]
• Efgartigimod serum concentrations from blood samples [Срок оценки: up to 26 weeks]
• Absolute values of levels of total Immunoglobulin G (IgG) from blood samples [Срок оценки: up to 26 weeks]
• Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples [Срок оценки: up to 26 weeks]
• Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples [Срок оценки: up to 26 weeks]
• Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [Срок оценки: up to 26 weeks]
• Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [Срок оценки: up to 26 weeks]
• Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [Срок оценки: up to 26 weeks]
• Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [Срок оценки: up to 28 weeks]
• Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: up to 26 weeks]

Критерии участия

Критерии включения

• 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).
• 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.
• Diagnosed with Generalized Myasthenia Gravis (gMG) with confirmed documentation
• Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, and IVa.
• 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.
• Positive serologic test for acetylcholine receptor (anti-AChR) antibodies at screening (for younger participants (<15kg) historical values can be used).
• 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.

• Male participants: Male participants must agree to not donate sperm from of providing informed consent/assent until they have completed the trial.
• 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.

Критерии исключения

• Participants with MGFA class I, IVb, and V.
• 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.
• Has any of the following medical conditions:

• Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening.
• 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.
• 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
• 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
• Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc).
• A documented lack of clinical response to plasma exchange (PLEX).
• 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.
• Received a thymectomy <3 months before screening or 1 is planned to be performed during the trial period.
• 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.

• 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.
• 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.
• A known hypersensitivity reaction to efgartigimod or any of its excipients.
• Current participation in another interventional clinical trial or previous participation in an efgartigimod trial with at least 1 dose of IMP received.
• History (within 12 months of screening) of current alcohol, drug, or medication abuse as assessed by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Ann and Robert H Lurie Children's Hospital of Chicago - Main Hospital — Chicago
• University of North Carolina at Chapel Hill — Chapel Hill
• University of Virginia (UVA) Health - Developmental Pediatrics Clinic — Charlottesville

Италия · 3 центра

• Azienda Ospedaliera Universitaria Policlinico Consorziale Di Bari — Bari
• Azienda Ospedaliero Universitaria A. Meyer — Florence
• Ospedale Giannina Gaslini — Genova

Польша · 3 центра

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Wielospecjalistyczna Poradnia Lekarska Synapsis — Katowice
• Centralny Szpital Kliniczny - Uniwersyteckie Centrum Kliniczne WUM — Warsaw

Великобритания · 3 центра

• Great Ormand Street Hospital for Children NHS Foundation Trust - Great Ormond Street Hospi — London
• Manchester University NHS Foundation Trust - Royal Manchester Children's Hospital — Manchester
• Oxford University Hospitals NHS Foundation Trust - John Radcliffe Hospital Children's Hosp — Oxford

Канада · 2 центра

• Alberta Childrens Hospital — Calgary
• British Columbia Children's Hospital — Vancouver

Франция · 2 центра

• AP-HM - Hopital de la Timone — Marseille
• Assistance Publique Hopitaux de Paris (AP-HP) - Hopital Necker-Enfants Malades — Paris

Грузия · 2 центра

• Vian - M. Iashvili Children's Central Hospital — Tbilisi
• Tbilisi State Medical University - Givi Zhvania Pediatric Academic Clinic — Tbilisi

Германия · 2 центра

• Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum - Sozialpadiatrisches Zentru — Berlin
• Universitätsklinikum Essen — Essen

Испания · 2 центра

• Hospital Sant Joan de Deu — Esplugues de Llobregat
• Hospital Universitari i Politecnic La Fe de Valencia — Valencia

Австрия · 1 центр

• Medizinische Universitat Wien — Vienna

Бельгия · 1 центр

• Universitair Ziekenhuis Antwerpen — Antwerp

Нидерланды · 1 центр

• Leids Universitair Medisch Centrum — Leiden

Идентификаторы

NCT: NCT04833894 · ARGX-113-2006 · 2024-513854-31-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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