Long-term Safety and Efficacy of Filgotinib in Patients with Idiopathic Multicentric Castleman's Disease (iMCD)

JRCT ID: jRCTs071230120

Registered date:04/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: idiopathic multicentric Castleman's disease
• Date of first enrollment: 04/03/2024
• Target sample size: 5
• Study type: Interventional
• Intervention(s): Filgotinib will be administered orally as one tablet of 200 mg once daily for 44 weeks.

Outcome(s)

Primary Outcome

The adverse event (Proportions of adverse events, serious adverse events, adverse drug reactions, adverse events leading to treatment discontinuation, and adverse events leading to death)
Laboratory tests (Hematology, biochemistry, CT scan (contrast-enhanced), 12 lead ECG, and qualitative urinalysis)

Secondary Outcome

The following items at Week 4 (12 weeks from the parent study), Week 10 (18 weeks), Week 18 (26 weeks), Week 26 (34 weeks), Week 34 (42 weeks), and Week 44 (52 weeks) of this research, taking Week 0 of the parent study as the baseline.
1.Change in CHAP score (CRP, hemoglobin, albumin, PS.) from baseline (2)
2.Change from Baseline in CRP (mg/dL)
3.Hemoglobin (g/dL) Change from Baseline
4.Change from Baseline in albumin (g/dL)
5.Change from Baseline in ECOG PS
6.Change from Baseline in Short-Form-36 (SF-36)
7.Change from Baseline in Physician's Global Assessment (100 mmVAS)
8.Change from baseline in Patient Global Assessment (100 mmVAS)
9.The proportion of patients achieving a 1-point reduction in CHAP score

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all of the following criteria will be included in the study.
(1) Patients who completed the 8-week treatment period with investigational product in the parent study.
(2) Patients aged 18 years or older who have received a sufficient explanation about the contents of the written information and other matters related to the study understood the contents and provided written voluntary consent to participate in this study. If the patient wishes to obtain a legally permissible representative, the patient has obtained written consent to participate in the research from the legally permissible representative who is likely to seek the patient's best interest.
(3) Women of childbearing potential must have a negative pregnancy test and must agree to use adequate contraception. Male subjects must agree to a reliable and acceptable method of contraception (Use of spermicide, condom, or abstinence). In both cases, it is mandatory to use contraception during the study period and until 30 days after the last dose of the study drug.

Exclude criteria

Subjects must not have at least one of the following;
(1) Known hypersensitivity to filgotinib maleate or significant allergic reaction to any drug
(2) Patients in whom the period from Week 8 of the parent study to the time of enrollment in the present research exceeds seven days
(3) 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 these diseases))
(4) Patients found to have HBV-DNA at or above the assay sensitivity by Week 8 in the parent study
(5) Uncontrolled infection (Tuberculosis, human immunodeficiency virus, etc. (but not limited to these diseases)). Patients with a positive QuantiFERON or T-SPOT result for IFN gamma release assay (IGRA) at screening of the parent study, who have no evidence of an active disease, may participate in the present study. Patients must have completed or received appropriate anti-tuberculosis treatment for latent tuberculosis infection.
(6) Patients with any of the following laboratory abnormalities at Week 8 in the parent study
1. Patients with estimated GFR<60 ml/min/1.73m2
2. Patients with moderate or severe hepatic impairment (equivalent to or higher than Child-Pugh class B)
3. Patients with neutrophil count < 1,000/mm3
4. Patients with lymphocyte count < 500/mm3
5. Hemoglobin < 8.0 g/dL
(7) Patients who meet the "Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype of idiopathic multicentric Castleman disease" (1) for definite iMCD-TAFRO
*Definite iMCD TAFRO: All 4 clinical criteria "Thrombocytopenia (less than or equal to 100,000 /microL), Anasarca (pleural effusion, ascites, subcutaneous edema on CT scan), pyrexia (higher than or equal to 37.5 degrees Celsius) or CRP higher than or equal to 2.0 mg/dL, organomegaly (2 or more areas of lymphadenopathy, hepatomegaly, splenomegaly on CT)" and pathological findings of lymph nodes that are consistent with the International iMCD diagnostic criteria as pathological criteria; additional findings that meet at least 1 of the 2 clinical or pathological criteria [Renal impairment (eGFR less than or equal to 60 mL/min/1.73 m2, Cr > 1.1 mg/dL (females), Cr > 1.3 mg/dL (males), or requiring dialysis) or bone marrow findings consistent with TAFRO syndrome (Reticulin fibrosis or megakaryocyte hyperplasia)] and exclude infection, autoimmune disease, or tumor
(8) Patients of either sex who wish to have children
(9) Pregnant women and lactating women
(10) Patients who are considered ineligible for the study by the investigator or subinvestigator

Related Information

• Primary Sponsor: Kawakami Atsushi
• Source(s) of Monetary Support: Gilead Sciences, Inc.