Investigator-Initiated Study of Filgotinib in Patients with Idiopathic Multicentric Castleman Disease (iMCD)
- Conditions
- idiopathic multicentric Castleman's diseaseCastleman's disease
- Registration Number
- JPRN-jRCT2071230108
- Lead Sponsor
- Kawakami Atsushi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 5
Patients who meet all of the following criteria will be included in the study.
(1) Patients aged >= 18 years and < 65 years at the time of informed consent
(2) Patients who meet the diagnostic criteria for idiopathic multicentric Castleman disease (Designated intractable disease [Notice No. 331] enforced on April 1, 2018 by the Ministry of Health, Labour and Welfare) at the time of enrollment (patients being treated must meet the diagnostic criteria at the time of enrollment.)
(3) Patients with a total CHAP score (CRP, hemoglobin, albumin, ECOG PS.) of >= 2 points in total with hemoglobin or albumin >= 1 point, and CRP >= 1 point at the screening examination
(4) Female of childbearing potential must have a negative pregnancy test and agree to use adequate contraception during the study and for 30 days after the last dose of investigational product. Male subjects must agree to a reliable and acceptable method of contraception (use of spermicide, condom or abstinence)
Subjects with any one of the following items are excluded.
(1) Known hypersensitivity to filgotinib maleate or history of severe allergic reaction to any drug
(2) Prior exposure to filgotinib
(3) Patients who have received tocilizumab within 28 days before enrollment. Patients on treatment with tocilizumab should discontinue at least 28 days prior to study entry.
(4) Patients with a history of malignancy within the last 5 years (with the exception of patients with non-melanoma skin cancer or carcinoma in situ of the cervix that has responded to treatment)
(5) History of lymphoproliferative disease other than iMCD, lymphoma, leukemia, myeloproliferative disease, or multiple myeloma
(6) Patients with autoimmune disease other than iMCD (Rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis/polymyositis, vasculitis, IgG4-related disease, Behcet's disease, etc. (but not limited to))
(7) Patients who were positive for HBs antigen (Patients who are negative for HBs antigen and positive for anti-HBs antibody and/or anti-HBc antibody could participate in this study.)
(8) Uncontrolled infection (Tuberculosis, human immunodeficiency virus, etc. (but not limited to)). Participants with a positive QuantiFERON or IFN-gamma release assay (IGRA, T-spot etc.) at screening with no evidence of an active disease could participate in the study. However, administration of appropriate anti-tuberculosis drugs should be started before administration of investigational product.
(9) Has any of the following laboratory abnormalities at screening:
- Patients with estimated GFR<60 ml/min/1.73 m2
- Patients with moderate or severe hepatic impairment (equivalent to or higher than Child-Pugh class B)
- Patients with neutrophil count < 1000/mm3
- Patients with lymphocyte count < 500/mm3
- Hemoglobin < 8.0 g/dL
(10)Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype of idiopathic multicentric Castleman disease for patients with definite iMCD-TAFRO with TAFRO signs
(11)Patients who started glucocorticoids within 14 days before enrollment (However, topical preparations and use of glucocorticoids for the treatment of iMCD are allowed.)
(12)Patients who have received immunosuppressants such as rituximab, sarilumab, or cyclophosphamide, TNF-alpha inhibitors such as infliximab, etanercept, adalimumab, golimumab, certolizumab, ozolarizumab, vedolizumab, or abatacept within 28 days before enrollment
(13)Patients who have received immunosuppressants (tacrolimus, cyclosporine, azathioprine, mizoribine, or sirolimus), JAK inhibitors (tofacitinib, baricitinib, peficitinib, upadacitinib, ruxolitinib, abrocitinib, ritrecitinib, or delgocitinib), or carotegrast within 14 days before enrollment (Topical use of immunosuppressants is permitted. Delgocitinib is approved only as a topical agent, but its concomitant use is prohibited.).
(14)Patients who have received a live vaccine within 7 days before enrollment and patients who are scheduled to receive a live vaccine from the enrollment date to the end date of the study
(15)Patients who have participated in another clinical study or clinical research within 8 weeks before enrollment
(16)Patients of either sex who wish to have children
(17)Patients who are less than 6 months postpartum at the time of enrollment, patients who have an abortion within 6 months before enrollment, and female patients who are lac
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The adverse event (Proportions of adverse events, serious adverse events, adverse drug reactions, adverse events leading to discontinuation of investigational product, and adverse events leading to death)<br>Laboratory tests (Complete blood count, blood biochemistry tests, contrast enhanced computed tomography, 12-lead ECG, and qualitative urinalysis)
- Secondary Outcome Measures
Name Time Method Set the following items at baseline and Weeks 2, 4, and 8.<br>(1) CHAP score (CRP, hemoglobin, albumin, PS) change from baseline<br>(2) Change from baseline in CRP (mg/dL)<br>(3) Change from baseline in hemoglobin (g/dL)<br>(4) Change from baseline in albumin (g/dL)<br>(5) Change from baseline in ECOG Performance Status <br>(6) Change from baseline in SF-36 <br>(7) Change from baseline in Physician's Global Assessment (100 mmVAS) <br>(8) Change from baseline in Patient's Global Assessment (100 mmVAS) <br>(9)Proportion of patients achieving a 1-point reduction in CHAP score at Week 8