Pharmacokinetics, Safety, and Tolerability of Filgotinib in Pediatric Patients with Juvenile Idiopathic Arthritis: A Multicenter, Open-Label Study
- Trial ID
- 2023-505844-21-00
- Protocol
- GLPG-0634-CL-131
- Sponsor
- Alfasigma S.p.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to characterize the **pharmacokinetics** of filgotinib in children and adolescents aged 8 to less than 18 years with active juvenile idiopathic arthritis (JIA). Understanding the pharmacokinetics is crucial for determining the appropriate dosing regimen, ensuring therapeutic efficacy, and minimizing potential adverse effects in this pediatric population.
Secondary objectives include:
- Evaluating the safety and tolerability of filgotinib in the same age group with active JIA. This is important to ensure that the treatment is not only effective but also safe for long-term use in children and adolescents.
- Assessing the acceptability of commercially developed film-coated tablets and minitablets in this demographic. This evaluation is essential to ensure that the medication is user-friendly and can be easily administered to young patients, which can significantly impact adherence to the treatment regimen.
Participants
The clinical trial involves a total of **5 participants** diagnosed with **juvenile idiopathic arthritis**. The study population comprises both male and female subjects aged between 8 to less than 18 years. Participants are required to have a body mass index within the 5th to 95th percentiles for their age and gender, ensuring a general health status that aligns with the World Health Organization standards. The trial population was selected based on their ability to comply with the study protocol and their history of inadequate response or intolerance to specific medications for juvenile idiopathic arthritis. Lifestyle considerations such as diet and physical activity are not explicitly detailed. The study includes a vulnerable population, as it involves children and adolescents. Key inclusion criteria include meeting the ILAR classification for specific categories of juvenile idiopathic arthritis and having moderately to severely active disease not adequately controlled with current therapy. Female participants of childbearing potential must have a negative pregnancy test and agree to use contraception if deemed sexually active and at risk for pregnancy.
Plans and Procedures
The clinical trial is designed as an open-label, multiple-dose, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of **filgotinib** in children and adolescents aged 8 to less than 18 years with juvenile idiopathic arthritis. The trial is categorized as a Phase 3 study and is not considered low intervention. The study will involve the administration of **filgotinib** in the form of film-coated tablets and mini-tablets, taken orally. The primary objective is to characterize the pharmacokinetic parameters of **filgotinib** and its major metabolite, GS-829845, including maximum observed plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval at steady state (AUC0-24,ss).
The trial is expected to commence recruitment on January 15, 2024, and is estimated to conclude by December 31, 2024. Participants will be involved in the study for the duration of the trial, with specific visits scheduled to monitor progress and collect data. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as age, body mass index, and disease activity. Follow-up visits will be conducted to assess the frequency and severity of treatment-emergent adverse events, as well as the acceptability of the medication using the Pediatric Oral Medicine Acceptability Questionnaire for Patients (POMAQ-P).
The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be made. Participants may be subject to early termination from the study if they experience serious treatment-emergent adverse events or if they are unable to comply with the study protocol. The trial will adhere to strict ethical guidelines, ensuring informed consent is obtained from participants or their legal guardians prior to any study-related procedures.
Treatment
The clinical trial involves the administration of **filgotinib**, an active substance of chemical origin, in various pharmaceutical forms. The first experimental medication is Jyseleca 100 mg film-coated tablets. These tablets are administered orally and are not formulated specifically for pediatric use. The dosage and frequency of administration are determined based on the study protocol, and participant compliance is monitored throughout the trial. The product is authorized under the marketing authorization number EU/1/20/1480/001 and is manufactured by Galapagos.
Another experimental medication used in the trial is GLPG0634, which is presented as film-coated mini-tablets. Like the Jyseleca 100 mg tablets, GLPG0634 is administered orally. This formulation is also not specifically designed for pediatric use. The product is identified by the sponsor product code GLPG0634 and is produced by Galapagos. The administration schedule and dosage are outlined in the study protocol, with compliance monitoring in place to ensure adherence to the treatment regimen.
The third experimental medication is Jyseleca 200 mg film-coated tablets, also containing **filgotinib** as the active ingredient. These tablets are administered orally and are not pediatric formulations. The product is authorized under the marketing authorization number EU/1/20/1480/003 and is manufactured by Galapagos. The administration and dosing schedule are specified in the clinical trial protocol, with participant compliance being closely monitored.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial data. The focus of the study is to evaluate the pharmacokinetics, safety, and tolerability of **filgotinib** in children and adolescents aged 8 to less than 18 years with juvenile idiopathic arthritis. The trial is open-label and involves multiple doses across multiple centers.
Efficacy
The efficacy of the clinical trial will be assessed through the evaluation of pharmacokinetic (PK) parameters of **filgotinib** and its major metabolite GS-829845. The primary endpoints include the maximum observed plasma concentration at steady state (Cmax,ss), the area under the plasma concentration-time curve over the dosing interval at steady state (AUC0-24,ss), and the area under the plasma concentration-time curve over the dosing interval at steady state for the effective exposure (AUCeff,ss). These parameters will provide insights into the drug's absorption, distribution, metabolism, and excretion in the target population.
Secondary endpoints will focus on the safety and tolerability of the treatment, including the frequency and severity of treatment-emergent adverse events (TEAEs), TEAEs of interest, serious TEAEs, and TEAEs leading to treatment discontinuation. Additionally, the acceptability of the commercially developed film-coated tablets and minitablets will be measured using the Pediatric Oral Medicine Acceptability Questionnaire for Patients (POMAQ-P). These assessments will be conducted at specified intervals throughout the trial to ensure comprehensive data collection and analysis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject and/or parent(s)/legal guardian must be able and willing to comply with the CSP requirements and must sign and date the informed consent form as approved by the IEC/IRB and as described in Section 12.7.2, prior to any screening evaluations.
- Subject with a body mass index (BMI) within the 5th to 95th percentiles for the age and gender (based on World Health Organization BMI charts, Appendix 3). Subject must have a minimum weight of 15 kg.
- Subject must be able and willing to comply with restrictions on prior and concomitant medication (as described in Section 6.3.2).
- Subject must meet the ILAR classification for 1 of the following categories and have, according to the investigator’s judgment, moderately to severely active disease that is not adequately controlled with his/her current therapy. a. RF-positive polyarthritis b. RF-negative polyarthritis c. Oligoarthritis d. Psoriatic arthritis e. ERA Note: Historical HLA-B27 results are considered appropriate for ERA diagnosis during screening. f. sJIA with active arthritis without active systemic features, or with active systemic features that are stable in the prior 6 months of time of enrollment
- Subject with intolerance or a history of inadequate response to at least one of the following medications for the treatment of JIA, administered for at least 12 weeks, based on current treatment guidelines: conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and bDMARDs (including MTX) and non-steroidal anti-inflammatory drugs for ERA and psoriatic arthritis.
- Female or male subjects from 8 to <18 years of age, on the date of signing the informed consent form (ICF).
- Female subjects of childbearing potential (i.e. who have passed menarche) must have a negative highly sensitive urine pregnancy test.
- Female subject of childbearing potential who are, in the opinion of the investigator, potentially sexually active and at risk for pregnancy, must agree to use contraception/preventive exposure measures (as described in Section 6.3.1.1.2).
- Female subject of non-childbearing potential must meet the definition in Section 6.3.1.1.1.
Exclusion Criteria
- Subject with persistent oligoarthritis.
- Subject with undifferentiated arthritis.
- Subject with any other any other rheumatic, inflammatory, or immunologic disease (e.g. inflammatory bowel disease, hypogammaglobulinemia, systemic lupus erythematosus, or uncontrolled uveitis).
- Subject has evidence of active HBV infection: subjects with positive HBsAg at screening are excluded from the study. Subjects with positive hepatitis B virus core antibody (HBcAb) and negative HBsAg require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBcAb and negative HBV DNA are eligible per investigator judgment but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care and require ongoing viral monitoring with blood tests for HBV DNA.
- Subject has chronic HCV infection, as defined by positive HCV Ab at screening and detectable HCV viremia. Subjects with positive HCV Ab must undergo reflex HCV RNA testing, and subjects with HCV RNA positivity will be excluded. Subjects with positive HCV Ab and negative HCV RNA are eligible per investigator judgment but require ongoing viral monitoring with blood tests for HCV RNA (see Section 8.3.2).
- Subject has a history of or a current immunosuppressive condition (e.g. HIV infection).
- Subject meets 1 of the following TB criteria at screening: • A history of active or currently active TB (regardless of treatment). • A positive QuantiFERON®-TB Gold Plus In-Tube test at screening. Note: If the test result is indeterminate, it may be repeated once; if indeterminate or positive on retest, subject is not eligible.
- Active infection that is clinically significant, as per judgment of the investigator.
- Subject with a history of complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, or central nervous system involvement).
- Currently on any therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex, or atypical mycobacteria).
- Subject presenting any signs or symptoms of SARS-Cov-2 infection, as detected at baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc.) (BMJ, 2020a, 2020b), should undergo testing, even if fully vaccinated against SARS-CoV-2, as per locally applicable standard criteria to diagnose SARS-CoV-2 infection, and be excluded if positive.
- Subject has a history of malignancy or myelo- or lymphoproliferative disorder prior to screening.
- Subject has a history or presence of clinically significant abnormalities detected on 12-lead electrocardiogram (ECG) of either rhythm or conduction e.g. known long QT syndrome or a QTcF >450 ms detected on the 12-lead ECG. A first-degree atrioventricular block will not be considered as a significant abnormality.
- Subject has any other condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- Subject with a history of macrophage activation syndrome within 6 months prior to the screening visit.
- Subject with psychological or cognitive difficulties that might interfere with study participation.
- Subject for whom results of the following laboratory tests performed at the central laboratory at screening meet any of the criteria below: a. Hemoglobin <8.0 g/dL (SI: <80 g/L) b. Neutrophils <1.05 x 10 3 3 cells/mm (SI: <1.05 x 10 9 cells/L) c. Lymphocytes <0.5 x 10 3 3 cells/mm (SI: <0.5 x 10 9 cells/L) d. ALT or AST >=1.5x ULN e. Total bilirubin level >=2x ULN unlessor >=3x ULN if the subject has been diagnosed with Gilbert's disease and this is clearly documented f. CrCl <60 mL/min/1.73 m 2 by the revised bedside Schwartz equation
- Subject has taken any prohibited therapies within the defined washout periods before the planned first dose of IP.
- Subject concurrently participates or participated in a drug, drug/device or biologic investigational research study within 4 weeks or 5 half-lives of the IP, whichever is longer, prior to the first dose.
- Subject has a known hypersensitivity to IP ingredients or history of a significant allergic reaction to IP ingredients as determined by the investigator.
- Female subject is pregnant or breast feeding or intending to become pregnant or breastfeed during the study.
- Investigator or other study staff or relative thereof who is directly involved in the conduct of the study.
- Subject has any condition or circumstances that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements (e.g. active alcohol or drug abuse).
- Subject has a history of chronic alcohol abuse, intravenous drug abuse, or other illicit drug abuse within the 2 years prior to screening.
- Subject is institutionalized by virtue of an order issued by either the judicial or the administrative authorities or has a dependence on the sponsor or investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 15 Jan 2024 | 10 |
 Germany | Not Recruiting | 15 Jan 2024 | 10 |
 Poland | Not Recruiting | 15 Jan 2024 | 10 |
 Spain | Not Recruiting | 15 Jan 2024 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Jyseleca 200 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | — | — | PRD9422638 |
GLPG0634 | Test | FILM-COATED MINI-TABLET | ORAL | — | — | PRD10583347 |
Jyseleca 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | — | — | PRD9422607 |