Changes in MTX-PG Concentrations During Subcutaneous MTX Therapy in Patients With Rheumatoid Arthritis(COSMOS Study)

Changes in Methotrexate Polyglutamate Concentrations When Changing From Oral to Subcutaneous Methotrexate Therapy in Methotrexate-naive Patients With Rheumatoid Arthritis: (COSMOS Study)

Methotrexate is known to exist intracellularly as methotrexate polyglutamate, which is formed by the addition of glutamic acid after absorption into the body.

The objective of this study is to measure the concentration of methotrexate polyglutamate in red blood cells and peripheral blood mononuclear cells after initiating methotrexate treatment in patients with rheumatoid arthritis who have no prior history of using methotrexate (either subcutaneous or oral formulations). Additionally, we aim to examine changes in methotrexate polyglutamate concentrations when switching from oral methotrexate to subcutaneous Metoject, as well as to investigate the relationship between methotrexate polyglutamate concentration and the efficacy and safety of the treatment. Another objective of this study is to evaluate whether switching to subcutaneous Metoject allows for an increased maximum tolerable dosage while maintaining safety.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Methotrexate (MTX)

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kaneko Yuko; Phone Number: +81-3-5363-3786; Email: ykaneko.z6@keio.jp

Study Locations

• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 35 Shinanomachi
      • Recruiting
      • Keio University Hospital
      • Contact: Yuko Kaneko; Phone Number: +81-3-5363-3786; Email: ykaneko.z6@keio.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Patients who were previously untreated with MTX, regardless of route of administration 2) Patients aged >=18 years at the time of informed consent 3) Patients who meet 2010 EULAR/ACR criteria 4) Patients who have disease activity of SDAI >11 at screening 5) Patients who were previously untreated with JAK inhibitor or bDMARDs 6) Female of child-bearing potential who can use appropriate contraceptive during the study and for at least one menstrual period after completion of MTX administration, female in whom time from menopause to informed consent is >=1 year, or female of no child-bearing potential through sterilization 7) Virile male who can use appropriate contraceptive during the study and for at least three months after completion of MTX administration 8) Patients who can adequately understand this study procedures, and voluntarily consent in writing to take part in this study

Exclusion Criteria:

• 1) Pregnant women or women who may be pregnant 2) Patients with a history of hypersensitivity to any ingredient of the study drug 3) Patients with serious hematologic and lymphatic disorders
• Patients with a history of myelodysplastic syndrome, aplastic anemia, or erythroblastoma
• Patients with a diagnosis or treatment of lymphoproliferative disease within the past 5 years
• Patients with significant leukopenia (white blood cell count <3000/mm3) or thrombocytopenia (platelet count <50000/mm3millimeter) 4) Patients with significant hepatic impairment
• Patients with acute or chronic active viral hepatitis B or C
• Patients diagnosed with cirrhosis
• Patients with other significant hepatic impairment (AST >150 U/L or ALT >150 U/L) 5) Patients with severe renal impairment The following criteria should be used as a reference.
• Dialysis patients or renal dysfunction correspon ding to renal glomerular filtration rate (GFR) <30 mL/min/1.73 m2 6) Patients who have pleural effusion or ascites 7) Patients who have active tuberculosis 8) Patients otherwise whom principal investigator/sub- investigator considered medically ineligible to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: MTX group	Drug: Methotrexate (MTX); Single arm study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in MTX-PG concentrations in erythrocytes from baseline	From enrollment to the end of treatment at 24 weeks

Collaborators and Investigators

• Sponsor: Keio University
• Collaborators: Eisai Co., Ltd.; Mebix Inc

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 30, 2025
• First Submitted That Met QC Criteria: April 4, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Methotrexate
• Other Study ID Numbers: N20240003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No