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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

22 Apr 2024 → ongoing

Decision date (initial)

2023-05-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Bundesministerium für Bildung und Forschung

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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 objectives 5

1. Secondary objectives are the further evaluation of the ALS related signs and symptoms.
2. Secondary objectives are safety and tolerability after the treatment with Rituximab.
3. Secondary objectives besides the clinical evaluation of motor deficits include assessment of BMI and the evaluation of the slow vital capacity score.
4. Secondary objectives are evaluation of laboratory parameters, evaluation of cognitive deficits
5. Adverse events and serious adverse events are monitored throughout the whole duration of the trial.

Conditions and MedDRA coding

Sporadic Amyotrophic Lateral Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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).
2. Age ≥ 18 years
3. Written consent to participate in the study
4. The patient is capable to attend study visits
5. 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.
6. Slow vital capacity (VC) equal to or more than 60% of the predicted normal value for gender, height and age at the screening visit
7. 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.
8. Patients with the capacity to give informed consent

Exclusion criteria 22

1. Dysfunction (other than ALS) that could distort or obscure the diagnosis of ALS.
2. Patients with a serious impairment of the immune system
3. Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled heart disease
4. Patients having severe disease in the renal, cardiovascular or hematological system
5. Patients with neutrophils < 1000 cells per µl and/or platelet counts 75.000 cells per µl
6. 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
7. Patients with other causes of neuromuscular weakness
8. Patients with severe active psychiatric illness
9. Patients with a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer’s disease)
10. Participation in any other investigational drug study or exposure to an investigational drug within 5 half-lives of the study drug at baseline
11. Patients with a history of recurrent or chronic infections or with underlying diseases which may further predispose patients to serious infection
12. 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
13. Hypersensitivity to the active substance, mouse proteins or sodium citrate, polysorbate 80
14. Known cytokine release syndrome after infusions
15. Hypersensitivity to the adjuvant medication (paracetamol, methylprednisolone and dimetinden maleate)
16. Pregnancy or lactation
17. The patient has used edaravone or sodium phenylbutyrate–taurursodiol in the first week before the baseline visit
18. 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
19. Patients with HIV infections
20. Active severe infections (e.g. tuberculosis, sepsis and opportunistic infections)
21. History of chronically active hepatitis including active or chronic hepatitis B, acute or chronic hepatitis C
22. Clinically significant infection involving intravenous administration of antibiotics and hospitalization in the 4 weeks prior to the screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 10

1. ALSFRS-R-SE change from baseline to 3, 27, 53, 105 and 131 weeks
2. Change in the slow vital capacity score (pulmonary fuction test) from baseline to 79 weeks
3. Change of BMI from baseline to 79 weeks
4. Tracheostomy-free survival at 79 weeks
5. Overall survival in Rituximab and standard therapy group
6. Laboratory parameters evaluating the safety of treatment with Rituximab
7. Serum and cerebrospinal fluid analyses with cell count, cytology, protein, glucose, lactate and infection markers
8. B cell counts
9. Neuropsychological tests (ECAS)
10. Quality of Life questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Sponsor organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Address

Venusberg-Campus 1/99, Venusberg Venusberg

City

Bonn

Postcode

53127

Country

Germany

Scientific contact point

Organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Contact name

Project Leader (Harald Prüß)

Public contact point

Organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Contact name

Project Leader (Harald Prüß)

Third parties 5

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications