RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— RIDOSE-MS  

Official title:

RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS. A Randomized Trial of Long-term Dosage of Rituximab in Multiple Sclerosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03979456
• Other study ID #: EudraCT 2018-000721-31
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 4, 2018
• Est. completion date: June 1, 2025

Study information

• Verified date: April 2021
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized trial of long-term dosage of rituximab in multiple sclerosis

Description:

This is a prospective randomized phase 3 study comparing two dosing regimens of Rituximab in long-term treatment of MS. Primary endpoint is no evidence of disease activity (NEDA) in a non-inferiority analysis between 12-months dosing interval of 500 mg rituximab with 6-months dosing interval. The endpoint is a compound of being free from release, new or enlarging MRI lesions and sustained progression of disability measured by EDSS. Each patient will have one treating physician responsible for all ongoing medical questions and decisions regarding continuation in the study and one examining physician performing the blinded Expanded Disability Status Scale examination and assessments of exacerbations. The coordinating nurse will administer the study-related tests and administer the rituximab infusions. MRI investigations will be performed blinded for the dosing arm allocation. Randomization will be performed via a randomization module in the national Swedish MS registry. The patients will be randomized in a 1:1 ratio and receive their treatments in accordance with clinical practice. Thus, the study will mimic the real-life situation in which the treatments will be administered. This will lead to a high degree of validity in relation to expected outcome in clinical practice.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: June 1, 2025
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 52 Years

Eligibility

Inclusion criteria:

• Diagnosis of Relapsing Remitting MS according to the 2017 revised McDonald criteria OR one demyelinating episode in conjunction with at least one asymptomatic high intensity T2 lesion with size and location compatible with MS
• The patient has completed the RIFUND-MS trial and is treated with either of the study medications rituximab or DMF at the last visit of the RIFUND trial OR has been treated with rituximab with a dose regimen of 500 - 1000 mg followed by 500 mg every 6 months for up to two years as part of clinical practice
• Age 20 - 52 years (inclusive)
• EDSS 0 - 5,5 (inclusive)
• The patient is willing and able to give written informed consent, according to the judgement of the investigator.
• In fertile females, willing to comply with effective contraceptive methods. These include birth control pills, surgical sterilization of patient or partner or intrauterine device. Non-fertile women is defined as more than 12 months of amenorrhea without an alternative medical cause or, in case of ambiguities, an FSH level in the postmenopausal range.

Exclusion criteria:

• Diagnosis of Progressive MS
• Previous treatment with any "second-line" immunomodulatory drug, eg natalizumab, alemtuzumab, fingolimod, or other long-acting immunosuppressive agents.
• Pregnant or lactating women s-HCG will be tested on all women at screening, before each study-related infu-sion and in any situation where there is a reason to suspect pregnancy during the trial, e.g delayed menstrual period more than five days above expected time.
• Patients having contraindication for or otherwise not compliant with MRI investigations
• Simultaneous treatment with other immunosuppressive drugs
• Active, severe infections Signs of infections are assessed before inclusion and each study-related infusion through clinical examination and further evaluated by laboratory and other relevant investigations in case of suspected ongoing infection. Hepatitis serology (HBsAg and anti-HBc) will be evaluated before treatment onset if not tested within the previous three years.
• Severe cardiac disorder, e.g signs of congestive heart failure or coronary artery disease. This will be evaluated through clinical assessment before inclusion.
• Vaccination within 4 weeks of first dose of study medication.
• Documented allergy or intolerance to the IP
• Severe psychiatric condition

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Rituximab
After one year in the trial, the patients are split in the two dosing-arms described above. The dose-comparison phase continues four years.

Locations

Country	Name	City	State
Sweden	South Älvsborg Hospital	Borås
Sweden	Anders Svenningsson	Danderyd	Stockholm
Sweden	Falun Hospital	Falun
Sweden	Gävle Hospital	Gävle
Sweden	Saghlgrenska Hospital	Göteborg
Sweden	Helsingborg Hospital	Helsingborg
Sweden	Karlstad Hospital	Karlstad
Sweden	Halland Hospital Kungsbacka	Kungsbacka
Sweden	Linköping University Hospital	Linköping
Sweden	Nyköping Hospital	Nyköping
Sweden	Örebro University Hospital	Örebro
Sweden	Östersund Hospital	Östersund
Sweden	Capio StGöran Hospital	Stockholm
Sweden	Fredrik Piehl	Stockholm
Sweden	Karolinska Hospital Huddinge	Stockholm
Sweden	Umeå University	Umeå
Sweden	Uppsala Academiska Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health economy	Estimation of societal costs per year to supply the two dosing arms	3 years
Other	Treatment Satisfaction Questionnaire	Validated scale that evaluate the degree of treatment satisfaction through 10 5- or 7 grade likert-scale questions	3 years
Primary	No evidence of disease activity (NEDA)	The proportion of patients maintaining No Evidence of Disease Activity-3 (NEDA-3) during year 2 - 4 of the trial: No relapse, no new T2 lesions (> 3 mm), no EDSS progression in either dose arm	3 years
Secondary	No evidence of disease activity (NEDA) in subgroups	The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial	4 years
Secondary	Time to first relapse	Time to first relapse for the two dose arms	3 yeas
Secondary	Freedom of new or enlarged lesions on MRI	Proportion of patients in each dosing arm without new/enlarging T2 lesions	3 years
Secondary	Development of brain atrophy	Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume	3 years
Secondary	Development of confirmed sustained disability	Proportion of patient with confirmed progression in EDSS according to pre-specified criteria	3 years
Secondary	Mean progression of disability	The mean change in EDSS over the trial period in the two dosing arms	3 years
Secondary	Neurodegeneration	The mean change of s-NFL concentration between the two dosing arms	3 years
Secondary	Dose persistence	Time to discontinuation of dosing regimen allocation	3 years
Secondary	Development of hypogammaglobulinaemia	The occurrence of hypogammaglobulinaemia in the two dosing arms	3 years
Secondary	Development of neutropenia	The occurrence of neutropenia in the two dosing arms	3 years
Secondary	Development of infections	The occurrence of infections in the two dosing arms	3 years