Drug Rediscovery for Rare Immune Mediated Inflammatory Diseases

Phase 2

Recruiting

Conditions: IgG4-related Disease
Behcet's Disease
Idiopathic Inflammatory Myopathies

Interventions: Drug: Filgotinib

Registration Number: NCT06285539

Lead Sponsor: UMC Utrecht

Brief Summary: Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) is limited due to small patient populations. Patients with Behçet's disease (BD), idiopathic inflammatory myopathy (IIM, also known as myositis) and IgG4-related disease (IgG4-RD) are treated with high-dosed glucocorticoids, methotrexate, azathioprine and mycophenolate mofetil, mostly for long periods of time with attendant risks of long-term toxicity, including infections. Therefore, there is an urgent need for new, more specific anti-inflammatory therapies such as targeted synthetic and biological disease-modifying antirheumatic drugs. Due to the role of type 1 interferon in both BD, IIM and IgG4-RD, JAK-STAT inhibition may be a promising treatment strategy in these conditions, because JAK1 is critical for the signal transduction of pro-inflammatory cytokine receptors. Previous research showed that JAK1 inhibition reduces activation of type 1 interferon-regulated proteins and key chemokines that control tissue inflammation.

Detailed Description: Not available

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 60

Inclusion Criteria

Age 18 years of older
One of the following rare IMIDs:
- Diagnosis of Behçet's disease without refractory life, organ or sight-threatening symptoms 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
- Diagnosis of idiopathic inflammatory myopathy, according to diagnostic criteria:

Dermatomyositis: Dermatomyositis Classification Criteria according to the European Neuromuscular Centre guidelines 201852 or anti-synthetase syndrome: Anti- synthetase syndrome Classification Criteria according to the European Neuromuscular Centre guidelines 200353, both with active disease, defined as 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 a 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

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
- Refractory disease, defined as symptomatic disease that persists despite a 12-week trial of glucocorticoid therapy as well as lack of response to at least 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: both a negative QuantiFERON-TB Gold (QFT-G) In-Tube test and a Mantoux tuberculin skin test performed at or within 3 months prior to screening and no signs suggestive of active TB infection as determined (and documented) by a qualified radiologist or pulmonologist as per local standard of care on a chest radiograph and no history of either untreated or inadequately treated latent or active TB infection.

Exclusion Criteria

Age <18 years
Age ≥65 years
Life expectancy less than 6 months
Juvenile DM, myositis overlapping with other autoimmune diseases, immune mediated necrotizing myopathy (IMNM), inclusion-body myositis or cancer-associated myositis
End-stage IIM wherein muscle weakness is most likely due to muscle damage, rather than myositis disease activity
Increased risk of major cardiovascular problems
Current smoker or smoked for a long time in the past
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.
Human Immunodeficiency Virus (HIV) infection
Presence of an active infection or viral hepatitis type B or C
History of shingles or recurrent herpes simplex infection
Concomitant malignancies or previous malignancies within the last five years (with exception of adequately treated basal or squamous cell carcinoma of the skin)
Increased risk of cancer
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Filgotinib	26 weeks of Filgotinib once daily, 200mg, orally,

Primary Outcome Measures

Name	Time	Method
Disease activity in myositis patients	26 weeks	Change from baseline in Total Improvement Score (TIS) of the International Myositis Assessment Clinical Studies (IMACS) group
Disease activity in IgG4-RD patients	26 weeks	Change from baseline in IgG4-RD responder index
EQ-5D-5L	26 weeks	Change from baseline in EuroQoL-5D-5L
Disease activity in Behcet's patients	26 weeks	Change from baseline in Behcet's Disease Current Activity Form (BDCAF)

Secondary Outcome Measures

Name	Time	Method
Treatment-related adverse events	26 weeks	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Corticosteroid dosage	26 weeks	Change from baseline in glucocorticoid dose
VAS score of pain	26 weeks	Change from baseline in pain scores on the Visual Analog Scale (0-100mm). A higher score is a worse outcome
Fatigue	26 weeks	Change from baseline in fatigue scores on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). A higher score is a worse outcome
Corticosteroid toxicity	26 weeks	Change from baseline in Glucocorticoid Toxicity Index (GTI)

Trial Locations

Locations (6): Hagaziekenhuis
🇳🇱
Den Haag, Netherlands
Radboud university medical center
🇳🇱
Nijmegen, Netherlands
Amsterdam UMC
🇳🇱
Amsterdam, Netherlands
Erasmus MC
🇳🇱
Rotterdam, Netherlands
University Medical Center
🇳🇱
Utrecht, Netherlands
Zuyderland Medical Center
🇳🇱
Heerlen, Netherlands

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