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

An Exploratory, Placebo-controlled, Double-blind, Phase II Study of the Efficacy and Safety for Rituximab (Genetical Recombination) in Myalgia Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

The efficacy and safety of rituximab on ME/CFS symptoms after administration to patients with myalgic encephalomyelitis/chronic fatigue syndrome will be compared in an exploratory, placebo-controlled, double-blind fashion. In the subsequent secondary evaluation period, subjects who received rituximab in the primary evaluation period will receive placebo, and the timing and duration of rituximab's effect will be explored throughout the entire evaluation period. Subjects who received placebo during the primary evaluation period will receive rituximab during the secondary evaluation period to explore changes in endpoints before and after switching from placebo to rituximab in the same subjects.

The efficacy and safety of rituximab (genetical recombination), a CD20 antibody, on ME/CFS symptoms after administration to patients with myalgic encephalomyelitis/chronic fatigue syndrome will be compared in an exploratory, placebo-controlled, double-blind fashion. In the subsequent secondary evaluation period, subjects who received rituximab in the primary evaluation period will receive placebo, and the timing and duration of rituximab's effect will be explored throughout the entire evaluation period. Subjects who received placebo during the primary evaluation period will receive rituximab during the secondary evaluation period to explore changes in endpoints before and after switching from placebo to rituximab in the same subjects.

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) based ME/CFS severity classification by the Ministry of Health, Labour and Welfare Research Group
3. Patients who are between 18 and 65 years of age at the time of obtaining written consent
4. Patients who can be hospitalized (hospitalized from the day before administration and discharged the day after administration) at the time of the first dose of each of 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 to components of rituximab or products derived from mouse protein

2. Patients whose cardiopulmonary function is judged by the treating physician to be not maintained

3. Patients complaining of fatigue that does not meet the diagnostic criteria for ME/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 human chorionic gonadotropin test) at the time of enrollment

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

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

8. Patients with a history of systemic immunosuppressive therapy (e.g., immunoglobulin therapy, azathioprine, cyclosporine, mycophenolate mofetil, etc.) within 1 year, a history of receiving drugs such as monoclonal antibodies acting on the immune system (e.g., anti-CD20 antibody products including rituximab), or a history of comorbidities requiring treatment with immunosuppressive drugs Patients with comorbidities requiring treatment with immunosuppressive agents (excluding treatment with 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 the investigational drug.

10. Patients with severe endogenous (primary) depression

11. Patients with a neutrophil count <1.5*103/microliter and platelet count <10.0*104/microliter on blood test

12. Patients with impaired renal function (serum creatinine level > 1.5 times the upper limit 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 of the 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-DNA quantification is confirmed to be negative (less than detection sensitivity) and for whom appropriate monitoring, etc. can be conducted in accordance with the Guidelines for Hepatitis B Treatment edited by the Japan Society of Hepatology.

    (ii) For patients with positive HCV antibody, when HCV-RNA quantification is negative (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 (except for observational studies without intervention) within 16 weeks prior to obtaining consent

18. Other patients who are judged by the investigator or subinvestigator (hereinafter referred to as investigator) to be inappropriate to participate in this clinical trial.