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

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ClinicalTrials.gov Identifier: NCT03979456
Recruitment Status : Recruiting
First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Sponsor:
Information provided by (Responsible Party):
Anders Svenningsson, Karolinska Institutet

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

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing-Remitting Drug: Rituximab Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS. A Randomized Trial of Long-term Dosage of Rituximab in Multiple Sclerosis
Actual Study Start Date : July 4, 2018
Estimated Primary Completion Date : December 20, 2024
Estimated Study Completion Date : June 1, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Active Comparator: 6-month dosing interval
This arm is receiving standard dose rituximab 500 mg every 6 months
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.
Other Name: Mabthera

Experimental: 12-month dosing interval
This arm is receiving the comparator dose rituximab 500 mg every 12 months
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.
Other Name: Mabthera




Primary Outcome Measures :
  1. No evidence of disease activity (NEDA) [ Time Frame: 3 years ]
    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 :
  1. No evidence of disease activity (NEDA) in subgroups [ Time Frame: 4 years ]
    The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial

  2. Time to first relapse [ Time Frame: 3 yeas ]
    Time to first relapse for the two dose arms

  3. Freedom of new or enlarged lesions on MRI [ Time Frame: 3 years ]
    Proportion of patients in each dosing arm without new/enlarging T2 lesions

  4. Development of brain atrophy [ Time Frame: 3 years ]
    Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume

  5. Development of confirmed sustained disability [ Time Frame: 3 years ]
    Proportion of patient with confirmed progression in EDSS according to pre-specified criteria

  6. Mean progression of disability [ Time Frame: 3 years ]
    The mean change in EDSS over the trial period in the two dosing arms

  7. Neurodegeneration [ Time Frame: 3 years ]
    The mean change of s-NFL concentration between the two dosing arms

  8. Dose persistence [ Time Frame: 3 years ]
    Time to discontinuation of dosing regimen allocation

  9. Development of hypogammaglobulinaemia [ Time Frame: 3 years ]
    The occurrence of hypogammaglobulinaemia in the two dosing arms

  10. Development of neutropenia [ Time Frame: 3 years ]
    The occurrence of neutropenia in the two dosing arms

  11. Development of infections [ Time Frame: 3 years ]
    The occurrence of infections in the two dosing arms


Other Outcome Measures:
  1. Health economy [ Time Frame: 3 years ]
    Estimation of societal costs per year to supply the two dosing arms

  2. Treatment Satisfaction Questionnaire [ Time Frame: 3 years ]
    Validated scale that evaluate the degree of treatment satisfaction through 10 5- or 7 grade likert-scale questions



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 52 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03979456


Contacts
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Contact: Anders Svenningsson, Professor 0046812355584 anders.svenningsson@ki.se

Locations
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Sweden
Anders Svenningsson Recruiting
Danderyd, Stockholm, Sweden, 18288
Contact: Anders Svenningsson, Professor    0046812355584    anders.svenningsson@ki.se   
South Älvsborg Hospital Recruiting
Borås, Sweden
Contact: Igal Rosenstein, MD         
Falun Hospital Recruiting
Falun, Sweden
Contact: Joakim Hambraeus, MD         
Gävle Hospital Recruiting
Gävle, Sweden
Contact: Irina Sjöblom         
Saghlgrenska Hospital Recruiting
Göteborg, Sweden
Contact: Jan Lycke, Professor         
Helsingborg Hospital Recruiting
Helsingborg, Sweden
Contact: Anette Risedal, MD         
Karlstad Hospital Recruiting
Karlstad, Sweden
Contact: Rune Johansson, MD         
Halland Hospital Kungsbacka Recruiting
Kungsbacka, Sweden
Contact: Eric Gilland, MD         
Linköping University Hospital Recruiting
Linköping, Sweden
Contact: Magnus Vrethem, Professor         
Nyköping Hospital Recruiting
Nyköping, Sweden
Contact: Jonas Lindeberg, MD         
Capio StGöran Hospital Recruiting
Stockholm, Sweden
Contact: Ahmad Ayad, MD         
Fredrik Piehl Recruiting
Stockholm, Sweden
Contact: Fredrik Piehl, Professor    +46 73-671 81 01    Fredrik.Piehl@ki.se   
Karolinska Hospital Huddinge Recruiting
Stockholm, Sweden
Contact: Katharina Fink, MD, PhD         
Umeå University Recruiting
Umeå, Sweden
Contact: Jonatan Saltzer, MD, PhD         
Uppsala Academiska Hospital Recruiting
Uppsala, Sweden
Contact: Joachim Burman, Assoc Prof         
Örebro University Hospital Recruiting
Örebro, Sweden
Contact: Martin Gunnarsson, Assoc Prof         
Östersund Hospital Recruiting
Östersund, Sweden
Contact: Pierre de Flon, MD, PhD         
Sponsors and Collaborators
Karolinska Institutet
Investigators
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Principal Investigator: Anders Svenningsson, Professor Dept of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm

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Responsible Party: Anders Svenningsson, Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03979456     History of Changes
Other Study ID Numbers: EudraCT 2018-000721-31
First Posted: June 7, 2019    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: June 2019

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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
Keywords provided by Anders Svenningsson, Karolinska Institutet:
Multiple sclerosis
Relapsing-Remitting
Dosing protocols
Randomized trial
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents