Study of the Efficacy and Safety for Rituximab in Myalgia Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Inclusion Criteria:

1. Patients diagnosed with ME/CFS who meet the Canadian criteria by a physician.

2. Patients with a severity score of 4 or higher on the Performance Status (PS) basedME/CFS severity classification by the Ministry of Health, Labour and WelfareResearch Group

3. Patients who are between 18 and 65 years of age at the time of obtaining writtenconsent

4. Patients who can be hospitalized (hospitalized from the day before administrationand discharged the day after administration) at the time of the first dose of eachof the primary and secondary evaluation periods

5. Patients whose written consent has been obtained

Exclusion Criteria:

1. Patients with a history of severe hypersensitivity or anaphylactic reactions tocomponents of rituximab or products derived from mouse protein

2. Patients whose cardiopulmonary function is judged by the treating physician to benot maintained

3. Patients complaining of fatigue that does not meet the diagnostic criteria forME/CFS

4. Patients found to have other medical conditions that may cause symptoms

5. Patients who are pregnant, lactating, or have a positive pregnancy test (serum humanchorionic gonadotropin test) at the time of enrollment

6. Patients with coexisting or pre-existing malignant tumors (excluding basal cellcarcinoma of the skin and cervical dysplasia)

7. Patients with coexisting or pre-existing severe immune system diseases (excludingautoimmune diseases such as thyroiditis and type 1 diabetes)

8. Patients with a history of systemic immunosuppressive therapy (e.g., immunoglobulintherapy, azathioprine, cyclosporine, mycophenolate mofetil, etc.) within 1 year, ahistory of receiving drugs such as monoclonal antibodies acting on the immune system (e.g., anti-CD20 antibody products including rituximab), or a history ofcomorbidities requiring treatment with immunosuppressive drugs Patients withcomorbidities requiring treatment with immunosuppressive agents (excluding treatmentwith low-dose steroids of 5 mg /day or less)

9. Patients who have started alternative medicine (reference: acupuncture, moxibustion,and Japanese warm therapy) within 12 weeks prior to the start of treatment with theinvestigational drug.

10. Patients with severe endogenous (primary) depression

11. Patients with a neutrophil count <1.5103/microliter and platelet count <10.0104/microliter on blood test

12. Patients with impaired renal function (serum creatinine level > 1.5 times the upperlimit of the reference value at the institution)

13. Patients with impaired hepatic function (serum bilirubin, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) levels exceeding 1.5 times the upper limit ofthe reference value of the institution)

14. Patients infected with Human Immunodeficiency Virus (HIV)

15. Patients who test positive for at least one of Hepatitis B surface (HBs) antigen,HBs antibody, Hepatitis B core (HBc) antibody, or Hepatitis C virus (HCV) antibody. However, patients who meet the following conditions (1) and (2) may be registered.

(i) Patients who are positive for HBs or HBc antibodies and whose HBV-DNAquantification is confirmed to be negative (less than detection sensitivity) and forwhom appropriate monitoring, etc. can be conducted in accordance with the Guidelinesfor Hepatitis B Treatment edited by the Japan Society of Hepatology.

(ii) For patients with positive HCV antibody, when HCV-RNA quantification isnegative (less than detection sensitivity)

16. Patients who do not have the ability to comply with the study protocol

17. Patients who have participated in other clinical trials or clinical studies (exceptfor observational studies without intervention) within 16 weeks prior to obtainingconsent

18. Other patients who are judged by the investigator or subinvestigator (hereinafterreferred to as investigator) to be inappropriate to participate in this clinicaltrial.