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

Phase 2RecruitingNCT06952413

National Center of Neurology and Psychiatry, Japan30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Myalgia Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Improvement rate

Percentage of cases in which the severity score of ME/CFS based on PS by the MHLW research group improved by 1 or more compared to that before the start of study drug administration (week 0)

Time frame: From Baseline to the end of treatment at 24 weeks

Secondary Outcomes

Percentage of patients whose MHLW-PS-based ME/CFS severity score improved by 1 or more at each evaluation point (improvement rate) compared to that before the start of treatment with the investigational drug (week 0).

Time frame: At 4-week intervals from Baseline up to Week 48

The amount of change in the severity score of ME/CFS based on PS by the MHLW Research Group at each assessment point from that before the start of treatment with the investigational drug (week 0)

Time frame: At 4-week intervals from Baseline up to Week 48

Proportion of awake time spent in supine position (%),Proportion of awake time spent in sitting position (%)

Changes in proportions will be aggregated.

Time frame: At 4-week intervals from Baseline up to Week 48

Duration of standing and activity (hours)

Changes in time will be aggregated.

Time frame: At 4-week intervals from Baseline up to Week 48

Fatigue during rest and lying position

Patients will be asked to report the level of fatigue they feel even while lying down, and changes in their fatigue levels will be aggregated.

Time frame: At 4-week intervals from Baseline up to Week 48

Records on exertion and Post-Exertional Malaise (PEM)

Patients will be asked to describe the specific activities they perform and the exhaustion they experience afterward, and a summary table will be created.

Time frame: At 4-week intervals from Baseline up to Week 48

Assessment of fatigue during physical activity

Patients will be asked to report the level of fatigue they experience during physical activity in daily life, and changes in fatigue levels will be aggregated.

Time frame: At 4-week intervals from Baseline up to Week 48

Evaluation based on Fatigue Score

Patients will be asked to complete the Fatigue Score questionnaire, and changes in the score will be aggregated.

Time frame: At 2-week intervals from Baseline up to Week 48

SF-36

Changes in scores obtained from the SF-36 questionnaire will be assessed to evaluate patients' quality of life.

Time frame: At 12-week intervals from Baseline up to Week 48

COMPASS31

Changes in scores obtained from the COMPASS31 questionnaire will be assessed to evaluate patients' autonomic symptoms.

Time frame: At 12-week intervals from Baseline up to Week 48

Pittsburgh Sleep Quality Index (PSQI)

Changes in scores obtained from the PSQI questionnaire will be assessed to evaluate patients' sleep quality.

Time frame: At 12-week intervals from Baseline up to Week 48

Pain intensity

Pain intensity will be assessed using the Visual Analogue Scale (VAS)

Time frame: At 12-week intervals from Baseline up to Week 48

Grip strength

Patients' grip strength will be measured, and changes in the measurements will be aggregated.

Time frame: At 12-week intervals from Baseline up to Week 48

Analysis of the gut microbiota

samples collected from patients will be analyzed, and the composition of the gut microbiota will be aggregated.

Time frame: At 24-week intervals from Baseline up to Week 48

Brain imaging evaluation (Magnetic Resonance Imaging (MRI) of the head, Single Photon Emission Computed Tomography (SPECT) of cerebral blood flow)

Findings from imaging will be aggregated.

Time frame: At 24-week intervals from Baseline up to Week 48

Immune biomarker analysis (qPCR)

qPCR will be measured, and changes in their levels will be aggregated.

Time frame: At 24-week intervals from Baseline up to Week 48

Immune biomarker analysis (anti-autonomic receptor antibody analysis)

Quantify the level of anti-autonomic receptor antibodies will be measured, and changes in their levels will be aggregated.

Time frame: At 24-week intervals from Baseline up to Week 48

Immune biomarker analysis (immune cell subfractionation analysis)

The subsets of immune cells will be measured, and changes in the levels will be aggregated.

Time frame: At 24-week intervals from Baseline up to Week 48

Metabolome analysis

A detailed characterization of the patients' metabolome at baseline will be conducted.

Time frame: At Baseline

Adverse events

The number of adverse events will be aggregated.

Time frame: From Baseline up to Week 48

Vital signs (body temperature)

Summary statistics of vital signs will be calculated to monitor changes over time.

Time frame: Assessments will be conducted at baseline and at Weeks 1, 2, 3, 4, 8, 12, 24, 25, 26, 27, 28, 32, 36, and 48

Vital signs (blood pressure)

Summary statistics of vital signs will be calculated to monitor changes over time.

Time frame: Assessments will be conducted at baseline and at Weeks 1, 2, 3, 4, 8, 12, 24, 25, 26, 27, 28, 32, 36, and 48

Vital signs (pulse rate)

Summary statistics of vital signs will be calculated to monitor changes over time.

Time frame: Assessments will be conducted at baseline and at Weeks 1, 2, 3, 4, 8, 12, 24, 25, 26, 27, 28, 32, 36, and 48

Serum immunoglobulins (IgG)

Summary statistics of serum immunoglobulins will be calculated to monitor changes over time.

Time frame: At 4-week intervals from Baseline up to Week 48

Serum immunoglobulins (IgM)

Summary statistics of serum immunoglobulins will be calculated to monitor changes over time.

Time frame: At 4-week intervals from Baseline up to Week 48

Serum immunoglobulins (IgA)

Summary statistics of serum immunoglobulins will be calculated to monitor changes over time.

Time frame: At 4-week intervals from Baseline up to Week 48

Rituximab concentration of the blood plasma

Time frame: Assessments will be conducted at baseline and at Weeks 1, 2, 3, 4, 12, 24, 25, 26, 27, 28, 36, and 48

Blood drug concentration Anti-Drug Antibody (ADA)

Summary statistics of ADA will be calculated to monitor changes over time.

Time frame: Assessments will be conducted at baseline and at Weeks 4, 12, 24, 28, 36, and 48.

B cells (CD19/CD20 positive cells) and T cells (CD3/CD4/CD8 positive cells)

Summary statistics of B cells and T cells will be calculated to monitor changes over time.

Time frame: Assessments will be conducted at baseline and at Weeks 1, 12, 24, 25, 36, and 48.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts