Evaluation of Filgotinib Efficacy and Safety in Refractory Idiopathic Inflammatory Myopathies, Behçet's Disease, and IgG4-Related Disease
- Trial ID
- 2022-502968-20-01
- Protocol
- 2022-502968-20-00
Trial statistics
Objectives
The primary objective of the study titled "Drug Rediscovery for rare Immune Mediated Inflammatory Diseases (DRIMID)" is to examine the **safety** and **efficacy** of filgotinib, an approved JAK-inhibitor, in patients with refractory Behcet's disease, Idiopathic Inflammatory Myopathies, and IgG4-related disease. This objective is clinically relevant as it aims to provide insights into the potential therapeutic benefits and risks of filgotinib in treating these rare and challenging conditions, which are often resistant to standard treatments. The study does not list any secondary objectives.
Participants
The clinical trial involves participants diagnosed with **Idiopathic Inflammatory Myopathies**, Behcet's disease, or IgG4-related disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have refractory disease, characterized by symptoms persisting despite a 12-week trial of corticoid therapy and lack of response to at least prednisone and one other immunosuppressive agent. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Participants must not have active or latent tuberculosis, as confirmed by a negative QuantiFERON-TB Gold test and a chest radiograph if necessary. The selection criteria ensure that participants have active disease, as defined by specific clinical and diagnostic criteria for each condition. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **efficacy** of **filgotinib**, a JAK-inhibitor, in patients with refractory Behcet's disease, idiopathic inflammatory myopathies, and IgG4-related disease. This is a Phase IV, randomized, double-blind, controlled trial. The trial is expected to last until April 2028, with recruitment starting in April 2023. Participants will be involved for a maximum treatment period of 26 weeks, during which they will receive either 100 mg or 200 mg of Jyseleca film-coated tablets orally, depending on the assigned group.
The study will include several visits, starting with a screening visit to assess eligibility based on criteria such as age, disease refractoriness, and absence of active or latent tuberculosis infection. Following successful screening, participants will be randomized and begin the treatment phase. Regular follow-up visits will be scheduled to monitor the primary endpoint, which is the EuroQol 5D-5L (EQ-5D-5L) form, and secondary endpoints, including the Behcet’s Disease Current Activity Form (BDCAF), Total Improvement Score, and IgG4-RD responder index, among others. The end-of-study visit will conclude the trial for each participant, assessing overall outcomes and any adverse events.
Participants are expected to adhere to the study protocol throughout the trial duration. Conditions that may lead to early termination from the study include non-compliance with the study protocol, development of exclusionary medical conditions, or withdrawal of consent. The trial aims to provide comprehensive data on the therapeutic potential of filgotinib in treating these rare immune-mediated inflammatory diseases.
Treatment
The clinical trial involves the administration of **Jyseleca 100 mg film-coated tablets**, which contain the active substance **filgotinib**. Filgotinib is a chemical compound classified under the ATC code L04AA45. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. The maximum daily dose for this formulation is 100 mg, with a total maximum dose of 6700 mg over a treatment period of 26 weeks. The tablets are manufactured by Galapagos and are not formulated for pediatric use. Participants are required to take the medication orally, and compliance with the dosing schedule is monitored throughout the trial.
Additionally, the trial includes the use of **Jyseleca 200 mg film-coated tablets**, also containing the active substance **filgotinib**. This formulation is similarly classified under the ATC code L04AA45 and is provided in a film-coated tablet form for oral administration. The maximum daily dose for the 200 mg formulation is 200 mg, with a total maximum dose of 36400 mg over the same 26-week treatment period. Like the 100 mg tablets, these are produced by Galapagos and are not intended for pediatric patients. The administration route is oral, and participant adherence to the dosing regimen is closely monitored to ensure compliance.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The focus of the study is to evaluate the safety and efficacy of filgotinib in patients with refractory Behçet's disease (BD), idiopathic inflammatory myopathies (IIM), and IgG4-related disease (IgG4-RD). The trial does not include any additional medications or interventions beyond the specified doses of Jyseleca tablets.
Efficacy
The clinical trial aims to assess the efficacy of **filgotinib**, a JAK-inhibitor, in patients with refractory Behçet’s disease (BD), idiopathic inflammatory myopathy (IIM), and IgG4-related disease (IgG4-RD). Efficacy will be evaluated using a combination of primary and secondary endpoints. The primary endpoint is the EuroQol 5D-5L (EQ-5D-5L) form, a standardized instrument for measuring health-related quality of life. Secondary endpoints include the Behçet’s Disease Current Activity Form (BDCAF), area under the curve (AUC) for the number of oral ulcers, Total Improvement Score, Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), IgG4-RD responder index, and the total number of flares in each disease, measured by a ≥1 point increase in Physician Global Assessment (PGA) on a scale from 0-3.
Additional secondary endpoints involve the Visual Analogue Scale (VAS) of disease activity, based on the clinical view of the local principal investigator, Glucocorticoid Toxicity Index (GTI), changes in glucocorticoid dose, VAS score of pain from the patient's perspective, Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F), Patient Acceptable Symptom State (PASS), and exposure-adjusted incidence rates for treatment-emergent adverse events. These endpoints will be measured and collected at various timepoints throughout the trial, with specific methods and schedules for each parameter. The trial is designed to provide comprehensive data on the efficacy of filgotinib in improving disease symptoms and quality of life in the target patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 18 years of older
- Refractory disease, defined as symptomatic disease that persists despite a 12-week trial of corticoid therapy as well as lack of response to at least prednisone and one other immunosuppressive agent such as methotrexate (MTX), mycophenolate mofetil (MMF), azathioprine (AZA) or rituximab or intolerance to standard-of-care treatment, as defined by the treating physician.
- No evidence of active or latent or inadequately treated infection with mycobacterium tuberculosis (TB) as defined by all of the following: (1) A negative QuantiFERON-TB Gold (QFT-G) In-Tube test performed at or within 3 months prior to screening. Subjects with a history of Bacille Calmette Guerin (BCG) vaccination will be tested with the QFT-G test and (2) No signs suggestive of active TB infection as determined (and documented) by a qualified radiologist or pulmonologist as per local standard of care and (3) no history of either untreated or inadequately treated latent or active TB infection. If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug resistant TB infection are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a purified protein derivative (PPD) test nor a QuantiFERON- TB Gold In TubeR™ (QFT Gold test) need be obtained, but a chest radiograph must be obtained if not done so within the prior three months.
- One of the following: (1) Diagnosis of Behçet’s disease without refractory life, organ or sight-threatening symtoms with active disease, defined as a BDCAF >2 (new BDCAF) or >15 (old BDCAF) or with active disease, based on clinical grounds (e.g. the need to start new or additional medication) or (2) Diagnosis of idiopathic inflammatory myopathy, according to diagnostic criteria: Dermatomyositis Classification Criteria according to the European Neuromuscular Centre guidelines 2018 or Anti-synthetase syndrome Classification Criteria according to the European Neuromuscular Centre guidelines 2003 with active disease, defined as: dermatomyositis with a CDASI score of ≥5 or abnormal levels of at least 1 of the following enzymes: creatine kinase (≥ 4× upper limit of normal [ULN]), aldolase (≥4× ULN), lactate dehydrogenase (LDH ≥4× ULN), aspartate transaminase (AST ≥4× ULN), alanine aminotransferase (ALT ≥4× ULN) or MRI within the last 3 months indicative of active inflammation (e.g. edema signal pattern in affected proximal muscles) or active disease based on clinical grounds, e.g. the need to start new or additional medication or (3) Diagnosis of IgG4-related disease, according to 2019 ACR/EULAR guidelines with active disease, defined as: IgG4-related disease responder index >10 or active disease based on clinical grounds, e.g. the need to start new or additional medication
Exclusion Criteria
- Age <18 years
- Life expectancy less than 6 months
- Juvenile DM, myositis overlapping with other autoimmune diseases, immune mediated necrotizing myopathy (IMNM) or cancer-associated myositis
- End-stage IIM wherein muscle weakness is most likely due to muscle damage, rather than myositis disease activity
- Pregnancy or lactation
- Previous use of other JAK-inhibitors
- Use of any investigational drug within one month prior to screening or within five half-lives of the investigational agent, whichever is longer.
- History of HIV
- Presence of an active infection or hepatitis
- History of VTE
- Concomitant malignancies or previous malignancies within the last five years (with exception of adequately treated basal or squamous cell carcinoma of the skin)
- Kidney injury with estimated glomerular filtration rate <15mL/min/1.73m2
- Liver failure Child Pugh C
- Absolute neutrophil count <1*109
- Absolute leukocyte count <0.5*109
- Hemoglobin <5mmol/L
- Inability to comply with study and/or follow-up procedures
- Known recent substance abuse (drugs or alcohol).
- Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
- Previous non-adherence to immunosuppressants
- Hypersensitivity to the active substance or to any of the excipients
- Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Yet Recruiting | 01 Apr 2023 | — |
| Netherlands | — | — | 60 |
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 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 100 | 26 | PRD9422607 |
Jyseleca 200 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 200 | 26 | PRD9422638 |