Evaluation of the efficacy and safety of Rituximab in patients with Amyotrophic Lateral Sclerosis (ALS)

Prior treatment

• Participation in any other investigational drug study or exposure to an investigational drug within 5 half-lives of the study drug at baseline
• Patients with a tracheostomy or ongoing treatment (more than 7 consecutive days in the 4 weeks prior to the screening visit) requiring noninvasive positive pressure ventilation of any kind
• Clinically significant infection involving intravenous administration of antibiotics and hospitalization in the 4 weeks prior to the screening visit

Other illness

• Patients with a history of recurrent or chronic infections or with underlying diseases which may further predispose patients to serious infection
• Known cytokine release syndrome after infusions
• Hypersensitivity to the adjuvant medication (paracetamol, methylprednisolone and dimetinden maleate)
• Patients with HIV infections
• Patients with a serious impairment of the immune system
• Active severe infections (e.g. tuberculosis, sepsis and opportunistic infections)
• History of chronically active hepatitis including active or chronic hepatitis B, acute or chronic hepatitis C
• Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled heart disease
• Patients having severe disease in the renal, cardiovascular or hematological system
• Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the trial or poses any added risk for the patient
• Patients with severe active psychiatric illness
• Patients with a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer’s disease)

Lab values

• Hypersensitivity to the active substance, mouse proteins or sodium citrate, polysorbate 80
• The patient has used edaravone or sodium phenylbutyrate–taurursodiol in the first week before the baseline visit
• Patients with neutrophils < 1000 cells per µl and/or platelet counts 75.000 cells per µl

Other

• Dysfunction (other than ALS) that could distort or obscure the diagnosis of ALS.
• Pregnancy or lactation
• Sexually active male and female patients of reproductive potential (female patients/ female partners of patients less than 12 months postmenopausal) who do not use highly effective contraception methods (pearl index <1) during and up to 12 months after treatment
• Patients with other causes of neuromuscular weakness

• Disease duration of sporadic ALS is ≤ 36 months after symptom onset and symptoms have not progressed to a permanent need of assisted ventilation of any kind (including non-invasive ventilation).
• Age ≥ 18 years
• Written consent to participate in the study
• The patient is capable to attend study visits
• Medication with riluzole at a stable dose of 50 mg BID for ≥ 30 days prior to the screening visit and if possible, throughout the study.
• Slow vital capacity (VC) equal to or more than 60% of the predicted normal value for gender, height and age at the screening visit
• Review of vaccination status and individual counseling according to STIKO guidelines. In case of missing vaccination, it is recommended to perform the vaccination parallel to the trial. Between vaccinations and Rituximab infusion, there should be an interval of four weeks (dose 1 at least four weeks before the first infusion, dose 2 four weeks before the third infusion). Decline of recommended vaccinations is acceptable only if participants have undergone a thorough informed consent process.
• Patients with the capacity to give informed consent