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

Phase 1

Recruiting

• Conditions: Sporadic Amyotrophic Lateral Sclerosis; MedDRA version: 21.1Level: PTClassification code: 10002026Term: Amyotrophic lateral sclerosis Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: CTIS2022-502743-35-00
• Lead Sponsor: Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-27
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Disease duration of sporadic ALS is = 24 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 75% of the predicted normal value for gender, height and age at the screening visit, Recommended standard vaccination according to STIKO (incl. COVID-19 vaccination). With the exception of Hepatitis B. Hepatitis B serology will be analysed at screening as to exclude an acute or underlying infection. In case of missing vaccination, it is recommended to perform the vaccination parallel to the trial (dose 1 before first infusion, dose 2 before third infusion)., Patients with the capacity to give informed consent

Exclusion Criteria

Dysfunction (other than ALS) that could distort or obscure the diagnosis of ALS., Patients with a serious impairment of the immune system, 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, Patients with neutrophils < 1000 cells per µl and/or platelet counts 75.000 cells per µl, 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 other causes of neuromuscular weakness, Patients with severe active psychiatric illness, Patients with a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer’s disease), 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 history of recurrent or chronic infections or with underlying diseases which may further predispose patients to serious infection, 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, Hypersensitivity to the active substance, mouse proteins or sodium citrate, polysorbate 80, Known cytokine release syndrome after infusions, Hypersensitivity to the adjuvant medication (paracetamol, methylprednisolone and dimetinden maleate), Pregnancy or lactation, The patient has used edaravone or sodium phenylbutyrate–taurursodiol in the first week before the baseline visit, 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 HIV infections, 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, History of a tuberculosis (TB) infection, signs/symptoms of TB or close contact with a person with an active TB infection, Clinically significant infection involving intravenous administration of antibiotics and hospitalization in the 4 weeks prior to the screening visit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the trial is to investigate if Rituximab as add-on treatment can reduce symptom progression in patients with ALS in comparison to standard therapy alone.;Secondary Objective: Secondary objectives are the further evaluation of the ALS related signs and symptoms., Secondary objectives are safety and tolerability after the treatment with Rituximab., Secondary objectives besides the clinical evaluation of motor deficits include assessment of BMI and the evaluation of the slow vital capacity score., Secondary objectives are evaluation of laboratory parameters, evaluation of cognitive deficits, Adverse events and serious adverse events are monitored throughout the whole duration of the trial.;Primary end point(s): ALS Functional Rating Scale - Revised – self-explenatory (ALSFRS-R-SE) change from baseline (first dose of study drug) to 79 weeks after administration of the first dose compared to standard therapy riluzole alone

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):ALSFRS-R-SE change from baseline to 3, 27, 53, 105 and 131 weeks;Secondary end point(s):Change in the slow vital capacity score (pulmonary fuction test) from baseline to 79 weeks;Secondary end point(s):Change of BMI from baseline to 79 weeks;Secondary end point(s):Tracheostomy-free survival at 79 weeks;Secondary end point(s):Overall survival in Rituximab and standard therapy group;Secondary end point(s):Laboratory parameters evaluating the safety of treatment with Rituximab;Secondary end point(s):Serum and cerebrospinal fluid analyses with cell count, cytology, protein, glucose, lactate and infection markers;Secondary end point(s):B cell counts;Secondary end point(s):Neuropsychological tests (ECAS);Secondary end point(s):Quality of Life questionnaire