Drug Rediscovery for Rare Immune Mediated Inflammatory Diseases

NCT06285539 | Recruiting Phase 2 DMC

• 1 other identifier: 2022-502968-20
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

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.

Conditions

Behcet's Disease; Idiopathic Inflammatory Myopathies; IgG4-related Disease

Keywords

JAK-inhibition

Outcome Measures

Primary Outcomes (4)

• EQ-5D-5L

  Change from baseline in EuroQoL-5D-5L

  26 weeks

• Disease activity in Behcet's patients

  Change from baseline in Behcet's Disease Current Activity Form (BDCAF)

  26 weeks

• Disease activity in myositis patients

  Change from baseline in Total Improvement Score (TIS) of the International Myositis Assessment Clinical Studies (IMACS) group

  26 weeks

• Disease activity in IgG4-RD patients

  Change from baseline in IgG4-RD responder index

  26 weeks

Secondary Outcomes (5)

• Corticosteroid toxicity

  26 weeks

• Corticosteroid dosage

  26 weeks

• VAS score of pain

  26 weeks

• Fatigue

  26 weeks

• Treatment-related adverse events

  26 weeks

Study Arms (1)

Intervention

EXPERIMENTAL

26 weeks of Filgotinib once daily, 200mg, orally,

Drug: Filgotinib

Interventions

Filgotinib DRUG

Filgotinib

Intervention

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Age \<18 years
• Age ≥65 years
• Life expectancy less than 6 months
• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• Alfasigma S.p.A.: collaborator
• ReumaNederland: collaborator
• Autoimmune Research and Collaboration Hub: collaborator

Study Sites (6)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Zuyderland Medical Center

Heerlen, Netherlands

RECRUITING

Radboud university medical center

Nijmegen, Netherlands

RECRUITING

Erasmus MC

Rotterdam, Netherlands

RECRUITING

Hagaziekenhuis

The Hague, Netherlands

RECRUITING

University Medical Center

Utrecht, Netherlands

RECRUITING

Related Publications (1)

• Geertsema-Hoeve BC, van Laar JAM, Raaphorst J, Tas SW, Welsing PMJ, Goekoop RJ, Checa CM, Thurlings RM, Rekers NH, Present E, van Laar JM. Multicentre, 26-week, open-label phase 2 trial of the JAK inhibitor filgotinib in Behcet's disease, idiopathic inflammatory myopathies and IgG4-related disease: DRIMID study protocol. BMJ Open. 2025 Feb 6;15(2):e089827. doi: 10.1136/bmjopen-2024-089827.

  PMID: 39915014 DERIVED

MeSH Terms

Conditions

Behcet Syndrome; Myositis; Immunoglobulin G4-Related Disease

Interventions

GLPG0634

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jaap M van Laar, Prof. dr.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Karien Marijnissen, Dr

CONTACT

+887550459; a.c.a.marijnissen@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: A 26-week multicenter, open-label, uncontrolled, non-randomized, non-blinded proof-of-concept, two-stage phase 2 study

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 29, 2024
• Study Start: March 12, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 26, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (6)