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A multicenter, Investigator-initiated Clinical Trial Comparing a Novel BRT therapy With Standard Therapy in Patients with Anti-MDA5-Antibody-Positive dermatomyositis who have multiple poor prognostic factors

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Patients with MDA5-DM-ILD who have multiple poor prognostic factors
Date of first enrollment	20/04/2026
Target sample size	44
Countries of recruitment
Study type	Interventional
Intervention(s)	Participants will be randomized in a 1:1 ratio to either the BRT therapy group (experimental group) or the standard therapy group (control group) and receive treatment. In addition, tacrolimus (TAC), methylprednisolone, and prednisolone will be administered as concomitant medications to both groups. Furthermore, for subjects in the control group, if no improvement is observed after the start of standard therapy and they meet the criteria for initiating adjunctive therapy, adjunctive therapy will be initiated; however, if no improvement is observed with adjunctive therapy, BRT therapy may be administered as rescue therapy. (BRT Therapy) Baricitinib (BAR) + Rituximab (recombinant) (RTX) (Standard Therapy) Cyclophosphamide (CYC) (Adjuvant Therapy) -Repeated steroid pulse therapy or steroid dose escalation -Plasmapheresis (PE) -High-dose intravenous immunoglobulin (IVIG) administration after PE, as needed

Outcome(s)

Primary Outcome

Overall survival: Defined as the period from the date of randomization to the date of death from any cause.

Secondary Outcome

1) Survival status at 6 months after randomization 2) Survival status at 12 months after randomization 3) Survival time without adjuvant therapy: The period from randomization to the date of initiation of adjuvant therapy, including re-pulse or re-escalation of steroids, plasma exchange, or IVIG 4) Progression-free survival: The period from randomization until the date on which the principal investigator or sub-investigator determined that the patient met the criteria for initiating adjuvant therapy, adjuvant therapy was administered, and the patient subsequently met the criteria for initiating adjuvant therapy again, and the principal investigator or sub-investigator determined that the disease had progressed 5) Duration of treatment: The period from randomization until the earlier of the date of initiation of rescue therapy or the date of initiation of subsequent therapy 6) Various relevant parameters: (1) Anti-MDA5 antibody (2) Ferritin (3) KL-6 (4) LDH (5) SpO2 (6) CRP 7) Presence or absence of ILD confirmed by imaging at 6 months post-randomization

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	< 80age old
Gender	Both
Include criteria	This study is intended for participants who meet all of the following inclusion criteria. 1) Patients who meet both criteria A) and B) of MDA5-DM A) Positive for anti-MDA5 antibodies B) Have any of the following a) Skin symptoms characteristic of dermatomyositis (Gottron's sign, heliotrope rash, periungual erythema, etc.) b) Dermatopathological findings consistent with dermatomyositis 2) Patients with rapidly progressive ILD within 3 months of the onset of symptoms who meet both criteria (1) and (2) below (1) Meet at least one of the following respiratory criteria - Increased respiratory rate (>= 20 breaths/min) - A decrease of 10% or more from the baseline %FVC - An increase of 15 mmHg or more in resting P[A-a]O2 from the baseline, or a decrease of 3% or more in SpO2 from the baseline - A decrease in SpO2 of 4% or more from the resting level during a 6-minute walk test - SpO2 < 94%, or SpO2/FiO2 ratio (S/F ratio) < 315 - PaO2 < 60 mmHg, or PaO2/FiO2 ratio (P/F ratio) < 300 (2) Meets the following criteria regarding imaging tests - Findings of acute exacerbation of interstitial pneumonia on chest HR-CT 3) Patients with at least one of the following poor prognostic factors A) through G) A) Anti-MDA5 antibody titer >= 500 Index B) Age >= 60 years C) SpO2 < 95% (room air) D) CRP >= 1 mg/dL E) Ferritin >= 500 ng/mL F) KL-6 >= 1000 IU/mL G) LDH >= 355 U/L 4) Patients with no prior treatment history with JAK inhibitors, including rituximab (recombinant) and baricitinib, for MDA5-DM 5) Patients who have completed methylprednisolone (mPSL) pulse therapy for MDA5-DM within one week prior to the start of Cycle 1 Day 1 (C1D1) of this clinical trial, and who have not yet received intravenous cyclophosphamide 6) Patients aged 18 years or older but under 80 years who have provided written informed consent to participate in the trial of their own free will If it is difficult to obtain consent directly from the patient at the time of consent acquisition, consent to participate in the trial may be obtained from a surrogate using the informed consent document.
Exclude criteria	1) Patients with MDA5-negative DM-ILD 2) Patients with conditions other than MDA5-DM, such as severe emphysema or concurrent malignancies, who have a poor prognosis regardless of control of the ILD 3) Patients with a history of severe hypersensitivity or anaphylaxis to any of the following: rituximab (recombinant), baricitinib, tacrolimus, or cyclophosphamide; to any component of these drugs; or to products derived from mouse proteins 4) Patients who are positive for one or more of the following: HBs antigen, HBs antibody, HBc antibody, or HCV antibody However, patients meeting the following criteria (1) and (2) may be enrolled. (1) Patients who are positive for HBs antibody or HBc antibody, provided that HBV-DNA quantification is negative (below the detection limit) and appropriate monitoring can be conducted in accordance with the "Guidelines for the Treatment of Hepatitis B" published by the Japan Society of Hepatology - For patients who are HBs antibody-positive and whose vaccination history can be confirmed via medical records, HBV-DNA testing is not required. - If testing was performed within 3 months prior to obtaining consent, those results may be accepted. (2) Patients who are HCV antibody-positive, provided that HCV-RNA quantification is negative (below the detection limit) 5) Patients with active tuberculosis However, patients who are IFN-gamma release assay (IGRA) positive or have an inconclusive result at the time of screening may be enrolled if they meet all of the following conditions (1) and (2). (1) Active tuberculosis has been ruled out by chest X-ray, CT, or other imaging (2) Appropriate treatment for latent tuberculosis has been initiated in accordance with domestic guidelines at least 3 weeks prior to the start of administration of the investigational drug 6) Patients diagnosed with HIV infection 7) Patients with severe infections (e.g., sepsis) 8) Patients with a white blood cell count of less than 2,500/mm3 9) Patients with a neutrophil count of less than 1,000/mm3 10) Patients with a lymphocyte count of less than 500/mm3 11) Patients with a hemoglobin level of less than 8 g/dL 12) Patients with a platelet count of less than 10.0 x 10^4/uL 13) Patients on dialysis or with severe renal impairment (eGFR < 30 mL/min/1.73 m2) 14) Patients showing signs of liver dysfunction, with either AST or ALT levels exceeding five times the upper limit of the facility's reference range 15) Cardiac: Patients with a left ventricular ejection fraction (LVEF) of less than 50%, or patients with an LVEF of 50% or higher who have heart disease classified as NYHA Class III or higher, or who have had a Grade 3 or higher myocardial infarction, arrhythmia, or angina within one year prior to enrollment 16) Patients with concurrent malignant tumors or a history of malignant tumors within the past 5 years 17) Pregnant women, patients who may be pregnant, patients of either sex who wish to conceive, or patients who are breastfeeding 18) Patients for whom hospitalization during the administration period of rituximab (recombinant) is difficult 19) Patients whom the principal investigator or sub-investigator determines are unable or have difficulty taking the investigational drug appropriately 20) Other patients whom the principal investigator or sub-investigator determines are unsuitable for participation in this clinical trial