Back to resultsRItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS (RIDOSE-MS)
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Active
Phase
Phase 3
Locations
Sweden
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting focused on measuring Multiple sclerosis, Relapsing-Remitting, Dosing protocols, Randomized trial
Eligibility Criteria
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
Sites / Locations
- Anders Svenningsson
- South Älvsborg Hospital
- Falun Hospital
- Gävle Hospital
- Saghlgrenska Hospital
- Helsingborg Hospital
- Karlstad Hospital
- Halland Hospital Kungsbacka
- Linköping University Hospital
- Nyköping Hospital
- Capio StGöran Hospital
- Fredrik Piehl
- Karolinska Hospital Huddinge
- Umeå University
- Uppsala Academiska Hospital
- Örebro University Hospital
- Östersund Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
6-month dosing interval
12-month dosing interval
Arm Description
This arm is receiving standard dose rituximab 500 mg every 6 months
This arm is receiving the comparator dose rituximab 500 mg every 12 months
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Time to first relapse
Time to first relapse for the two dose arms
Freedom of new or enlarged lesions on MRI
Proportion of patients in each dosing arm without new/enlarging T2 lesions
Development of brain atrophy
Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume
Development of confirmed sustained disability
Proportion of patient with confirmed progression in EDSS according to pre-specified criteria
Mean progression of disability
The mean change in EDSS over the trial period in the two dosing arms
Neurodegeneration
The mean change of s-NFL concentration between the two dosing arms
Dose persistence
Time to discontinuation of dosing regimen allocation
Development of hypogammaglobulinaemia
The occurrence of hypogammaglobulinaemia in the two dosing arms
Development of neutropenia
The occurrence of neutropenia in the two dosing arms
Development of infections
The occurrence of infections in the two dosing arms
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03979456
Brief Title
RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 4, 2018 (Actual)
Primary Completion Date
December 20, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A randomized trial of long-term dosage of rituximab in multiple sclerosis
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
Keywords
Multiple sclerosis, Relapsing-Remitting, Dosing protocols, Randomized trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
6-month dosing interval
Arm Type
Active Comparator
Arm Description
This arm is receiving standard dose rituximab 500 mg every 6 months
Arm Title
12-month dosing interval
Arm Type
Experimental
Arm Description
This arm is receiving the comparator dose rituximab 500 mg every 12 months
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
After one year in the trial, the patients are split in the two dosing-arms described above. The dose-comparison phase continues four years.
Primary Outcome Measure Information:
Title
No evidence of disease activity (NEDA)
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
No evidence of disease activity (NEDA) in subgroups
Description
The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial
Time Frame
4 years
Title
Time to first relapse
Description
Time to first relapse for the two dose arms
Time Frame
3 yeas
Title
Freedom of new or enlarged lesions on MRI
Description
Proportion of patients in each dosing arm without new/enlarging T2 lesions
Time Frame
3 years
Title
Development of brain atrophy
Description
Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume
Time Frame
3 years
Title
Development of confirmed sustained disability
Description
Proportion of patient with confirmed progression in EDSS according to pre-specified criteria
Time Frame
3 years
Title
Mean progression of disability
Description
The mean change in EDSS over the trial period in the two dosing arms
Time Frame
3 years
Title
Neurodegeneration
Description
The mean change of s-NFL concentration between the two dosing arms
Time Frame
3 years
Title
Dose persistence
Description
Time to discontinuation of dosing regimen allocation
Time Frame
3 years
Title
Development of hypogammaglobulinaemia
Description
The occurrence of hypogammaglobulinaemia in the two dosing arms
Time Frame
3 years
Title
Development of neutropenia
Description
The occurrence of neutropenia in the two dosing arms
Time Frame
3 years
Title
Development of infections
Description
The occurrence of infections in the two dosing arms
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Health economy
Description
Estimation of societal costs per year to supply the two dosing arms
Time Frame
3 years
Title
Treatment Satisfaction Questionnaire
Description
Validated scale that evaluate the degree of treatment satisfaction through 10 5- or 7 grade likert-scale questions
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
52 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Svenningsson, Professor
Organizational Affiliation
Dept of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anders Svenningsson
City
Danderyd
State/Province
Stockholm
ZIP/Postal Code
18288
Country
Sweden
Facility Name
South Älvsborg Hospital
City
Borås
Country
Sweden
Facility Name
Falun Hospital
City
Falun
Country
Sweden
Facility Name
Gävle Hospital
City
Gävle
Country
Sweden
Facility Name
Saghlgrenska Hospital
City
Göteborg
Country
Sweden
Facility Name
Helsingborg Hospital
City
Helsingborg
Country
Sweden
Facility Name
Karlstad Hospital
City
Karlstad
Country
Sweden
Facility Name
Halland Hospital Kungsbacka
City
Kungsbacka
Country
Sweden
Facility Name
Linköping University Hospital
City
Linköping
Country
Sweden
Facility Name
Nyköping Hospital
City
Nyköping
Country
Sweden
Facility Name
Capio StGöran Hospital
City
Stockholm
Country
Sweden
Facility Name
Fredrik Piehl
City
Stockholm
Country
Sweden
Facility Name
Karolinska Hospital Huddinge
City
Stockholm
Country
Sweden
Facility Name
Umeå University
City
Umeå
Country
Sweden
Facility Name
Uppsala Academiska Hospital
City
Uppsala
Country
Sweden
Facility Name
Örebro University Hospital
City
Örebro
Country
Sweden
Facility Name
Östersund Hospital
City
Östersund
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS
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