Drug Rediscovery for rare Immune Mediated Inflammatory Diseases (DRIMID)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2023-06-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To examine the safety and efficacy of filgotinib, an approved JAK-inhibitor in patients with refractory BD, IIM and IgG4-RD.

Conditions and MedDRA coding

Idiopathic Inflammatory Myopathies

Study design 6 periods

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age 18 years of older
2. 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.
3. 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.
4. 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 22

1. Age <18 years
2. Life expectancy less than 6 months
3. Juvenile DM, myositis overlapping with other autoimmune diseases, immune mediated necrotizing myopathy (IMNM) or cancer-associated myositis
4. End-stage IIM wherein muscle weakness is most likely due to muscle damage, rather than myositis disease activity
5. Pregnancy or lactation
6. Previous use of other JAK-inhibitors
7. Use of any investigational drug within one month prior to screening or within five half-lives of the investigational agent, whichever is longer.
8. History of HIV
9. Presence of an active infection or hepatitis
10. History of VTE
11. Concomitant malignancies or previous malignancies within the last five years (with exception of adequately treated basal or squamous cell carcinoma of the skin)
12. Kidney injury with estimated glomerular filtration rate <15mL/min/1.73m2
13. Liver failure Child Pugh C
14. Absolute neutrophil count <1*109
15. Absolute leukocyte count <0.5*109
16. Hemoglobin <5mmol/L
17. Inability to comply with study and/or follow-up procedures
18. Known recent substance abuse (drugs or alcohol).
19. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
20. Previous non-adherence to immunosuppressants
21. Hypersensitivity to the active substance or to any of the excipients
22. Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EuroQol 5D-5L (EQ-5D-5L) form

Secondary endpoints 13

1. Behҫet’s Disease Current Activity Form (BDCAF)
2. AUC for number of oral ulcers
3. Total Improvement Score
4. Cutaneous Dermatomyositis Disease Area and Severity index (CDASI)
5. IgG4-RD responder index
6. Total number of flares in each disease, measured by a ≥1 point increase in Physician Global Assessment (PGA) on a scale from 0-3
7. Visual Analogue Scale (VAS) of disease activity, based on the clinical view of the local principal investigator
8. Glucocorticoid Toxicity Index (GTI)
9. Changes in glucocorticoid dose
10. VAS score of pain, patients perspective
11. Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F)
12. Patient Acceptable Symptom State (PASS)
13. Exposure-adjusted incidence rates for treatment-emergent adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Utrecht

Sponsor organisation

University Medical Center Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

University Medical Center Utrecht

Contact name

Prof. dr. J.M. van Laar

Public contact point

Organisation

University Medical Center Utrecht

Contact name

Prof. dr. J.M. van Laar

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications