Back to resultsTapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis (RITUXERA)
Primary Purpose
Rheumatoid Arthritis
Status
Not yet recruiting
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Rituximab, Tapering, Disease impact
Eligibility Criteria
Inclusion Criteria: Able and willing to give written informed consent and participate in the study before any study procedure. Age ≥ 18 years. Understanding and able to write in Dutch or French. Diagnosis of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for rheumatoid arthritis. Previous response to rituximab, defined as a minimum of one successful rituximab cycle (= a moderate/good EULAR response 16 weeks after the first administration of rituximab). Current treatment with rituximab. Need for a subsequent rituximab cycle according to the Belgian reimbursement criteria for the use of rituximab in rheumatoid arthritis (DAS28 score ≥3.2). Stable dose of methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) 4 weeks prior to baseline. Exclusion Criteria: Current treatment with another biological DMARD than rituximab. Current treatment with a targeted synthetic DMARD. Pregnancy or pregnancy wish.
Sites / Locations
- ZNA Jan Palfijn
- Reumacentrum Genk
- ReumaClinic Genk
- OLV Aalst
- RZ Heilig Hart
- University Hospitals Leuven (UZ Leuven)
- Cliniques Universitaires Saint-Luc Bruxelles
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tapering of rituximab based on disease activity guided dose reduction
Tapering of rituximab based on interval prolongation
Arm Description
Treatment with rituximab every 6 months (24 weeks) with dosing based on disease activity, measured by the DAS28-CRP. DAS28-CRP ≤ 3.2: dose reduction according to the following sequence: 1 x 1000 mg IV (maximum), 1 x 500 mg IV, 1 x 200 mg IV (minimum). DAS28-CRP > 3.2: administration of previously effective dose.
Treatment with fixed dose of rituximab (1 x 1000 mg IV) if DAS28-CRP ≥ 3.2 AND interval of at least 6 months (24 weeks) since previous administration of rituximab.
Outcomes
Primary Outcome Measures
Comparison of disease impact in both study arms, measured using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire
RAID questionnaire score range: 0 - 10, with higher scores indicating worse status.
Secondary Outcome Measures
Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)
Main secondary outcome. DAS28-CRP range: 0 - ..., with higher values indicating higher disease activity.
Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)
SDAI range: 0 - ..., with higher values indicating higher disease activity.
Comparison of cumulative dose of rituximab in both study arms
Comparison of cumulative dose of glucocorticoids in both study arms
Proportion of patients in both study arms achieving a good or moderate European League Against Rheumatism (EULAR) treatment response after administration of rituximab, over a period of 2 years (104 weeks)
A good EULAR response is defined as a decrease in Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 1.2 and a present DAS-CRP ≤ 3.2. A moderate EULAR response is defined as a decrease in DAS28-CRP > 0.6 to ≤ 1.2 and a present DAS28-CRP ≤ 5.1, or a decrease in DAS28-CRP > 1.2 and a present DAS28-CRP > 3.2. Treatment responses will be evaluated 12 weeks after every administration of rituximab.
Comparison of loss of disease control in both study arms
Loss of disease control is defined as achieving a Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 3.2 with previous DAS28-CRP ≤ 3.2.
Comparison of rituximab drug retention rate in both study arms
Defined as the percentage of patients remaining on treatment with rituximab over time.
Proportion of patients tapering rituximab below 1000 mg in the experimental arm
Mean/median interval between rituximab administrations in the active comparator group
Full Information
NCT ID
NCT06003283
First Posted
July 19, 2023
Last Updated
August 17, 2023
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Fonds voor Wetenschappelijk Reumaonderzoek (FWRO)
1. Study Identification
Unique Protocol Identification Number
NCT06003283
Brief Title
Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis
Acronym
RITUXERA
Official Title
Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis: The RITUXERA Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
November 1, 2026 (Anticipated)
Study Completion Date
November 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Fonds voor Wetenschappelijk Reumaonderzoek (FWRO)
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
No
5. Study Description
Brief Summary
The goal of this open label multicenter randomized controlled pragmatic superiority trial is to investigate the optimal treatment/tapering strategy with rituximab for patients with rheumatoid arthritis.
The main questions it aims to answer are:
What is the optimal treatment/tapering strategy for rituximab in patients with rheumatoid arthritis in terms of reducing patient reported disease impact?
What is the optimal treatment/tapering strategy for rituximab in patients with rheumatoid arthritis in terms of therapeutic efficacy?
Participants will be randomized to one of two study arms:
Tapering based on disease-activity guided dose reduction (experimental arm)
Tapering based on interval prolongation (active comparator arm)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Rituximab, Tapering, Disease impact
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Open label multicenter pragmatic randomized controlled superiority trial. Patients will be 1:1 randomized to either the experimental arm or the active comparator arm.
Study visits are scheduled every 12 weeks (3 months). Recruitment period: 1 year. Trial duration: 2 years.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tapering of rituximab based on disease activity guided dose reduction
Arm Type
Experimental
Arm Description
Treatment with rituximab every 6 months (24 weeks) with dosing based on disease activity, measured by the DAS28-CRP.
DAS28-CRP ≤ 3.2: dose reduction according to the following sequence: 1 x 1000 mg IV (maximum), 1 x 500 mg IV, 1 x 200 mg IV (minimum).
DAS28-CRP > 3.2: administration of previously effective dose.
Arm Title
Tapering of rituximab based on interval prolongation
Arm Type
Active Comparator
Arm Description
Treatment with fixed dose of rituximab (1 x 1000 mg IV) if DAS28-CRP ≥ 3.2 AND interval of at least 6 months (24 weeks) since previous administration of rituximab.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera, Truxima, Ruxience, Rixathon
Intervention Description
IV rituximab
Primary Outcome Measure Information:
Title
Comparison of disease impact in both study arms, measured using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire
Description
RAID questionnaire score range: 0 - 10, with higher scores indicating worse status.
Time Frame
Over 2 years (104 weeks)
Secondary Outcome Measure Information:
Title
Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)
Description
Main secondary outcome. DAS28-CRP range: 0 - ..., with higher values indicating higher disease activity.
Time Frame
Over 2 years (104 weeks)
Title
Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)
Description
SDAI range: 0 - ..., with higher values indicating higher disease activity.
Time Frame
Over 2 years (104 weeks)
Title
Comparison of cumulative dose of rituximab in both study arms
Time Frame
Over 2 years (104 weeks)
Title
Comparison of cumulative dose of glucocorticoids in both study arms
Time Frame
Over 2 years (104 weeks)
Title
Proportion of patients in both study arms achieving a good or moderate European League Against Rheumatism (EULAR) treatment response after administration of rituximab, over a period of 2 years (104 weeks)
Description
A good EULAR response is defined as a decrease in Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 1.2 and a present DAS-CRP ≤ 3.2. A moderate EULAR response is defined as a decrease in DAS28-CRP > 0.6 to ≤ 1.2 and a present DAS28-CRP ≤ 5.1, or a decrease in DAS28-CRP > 1.2 and a present DAS28-CRP > 3.2. Treatment responses will be evaluated 12 weeks after every administration of rituximab.
Time Frame
Over 2 years (104 weeks)
Title
Comparison of loss of disease control in both study arms
Description
Loss of disease control is defined as achieving a Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 3.2 with previous DAS28-CRP ≤ 3.2.
Time Frame
Over 2 years (104 weeks)
Title
Comparison of rituximab drug retention rate in both study arms
Description
Defined as the percentage of patients remaining on treatment with rituximab over time.
Time Frame
Over 2 years (104 weeks)
Title
Proportion of patients tapering rituximab below 1000 mg in the experimental arm
Time Frame
Over 2 years (104 weeks)
Title
Mean/median interval between rituximab administrations in the active comparator group
Time Frame
Over 2 years (104 weeks)
Other Pre-specified Outcome Measures:
Title
Comparison of functional status in both study arms, measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Description
HAQ-DI score range: 0 - 3, with higher scores indicating worse functional status.
Time Frame
Over 2 years (104 weeks)
Title
Self-efficacy in both study arms, measured using the Arthritis Self-Efficacy Scale (ASES)
Description
ASES score range: 11 - 110, with higher scores indicating higher perceived self-efficacy.
Time Frame
Over 2 years (104 weeks)
Title
Pain in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
Description
VAS pain range: 0 - 100, with higher values indicating higher pain
Time Frame
Over 2 years (104 weeks)
Title
Fatigue in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
Description
VAS fatigue range: 0 - 100, with higher values indicating more fatigue.
Time Frame
Over 2 years (104 weeks)
Title
Patient global assessment (PGA) of disease in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
Description
VAS PGA range: 0 - 100, with higher values indicating worse disease.
Time Frame
Over 2 years (104 weeks)
Title
(Serious) infection rate in both study arms
Description
An infection is considered serious if it leads to inpatient hospitalization or prolongation of existing hospitalization, if it results in persistent or significant disability or incapacity, if it results in a life-threatening experience (meaning that the subject was at risk of death), or if it results in death.
Time Frame
Over 2 years (104 weeks)
Title
Cluster of Differentiation (CD) 19+ and Memory B cell counts in both study arms
Description
Determined at baseline, before administration of rituximab and at year 2 (104 weeks) in both study arms.
Time Frame
Over 2 years (104 weeks)
Title
Immunoglobulin (Ig) counts (IgG, IgA and IgM) in both study arms
Description
Determined at baseline, before administration of rituximab and at year 2 (104 weeks) in both study arms.
Time Frame
Over 2 years (104 weeks)
Title
Professional and vocational participation in both study arms, calculated using the Work Productivity and Activity Impairment questionnaire: General Health (WPAI:GH)
Description
The WPAI:GH calculates the percent work time missed due to health, the percent impairment while working due to health, the percent overall work impairment due to health, and the percent activity impairment due to health.
Time Frame
Over 2 years (104 weeks)
Title
Health utility index in both study arms, calculated using the summary index score of the EuroQol - 5 dimensions (EQ-5D) questionnaire
Description
Summary index score range: less than 0 (health state worse than dead, 0 being the value of a health state equivalent to death) to 1 (full health).
Time Frame
Over 2 years (104 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Able and willing to give written informed consent and participate in the study before any study procedure.
Age ≥ 18 years.
Understanding and able to write in Dutch or French.
Diagnosis of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for rheumatoid arthritis.
Previous response to rituximab, defined as a minimum of one successful rituximab cycle (= a moderate/good EULAR response 16 weeks after the first administration of rituximab).
Current treatment with rituximab.
Need for a subsequent rituximab cycle according to the Belgian reimbursement criteria for the use of rituximab in rheumatoid arthritis (DAS28 score ≥3.2).
Stable dose of methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) 4 weeks prior to baseline.
Exclusion Criteria:
Current treatment with another biological DMARD than rituximab.
Current treatment with a targeted synthetic DMARD.
Pregnancy or pregnancy wish.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patrick Verschueren, MD, PhD
Phone
016342541
Ext
+32
Email
patrick.verschueren@uzleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
Johan Joly, MSc
Phone
016340258
Ext
+32
Email
johan.joly@uzleuven.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Verschueren, MD, PhD
Organizational Affiliation
University Hospitals Leuven/KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
ZNA Jan Palfijn
City
Merksem
State/Province
Antwerpen
ZIP/Postal Code
2170
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alla Ishchenko, MD
Facility Name
Reumacentrum Genk
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philip Remans, MD, PhD
Facility Name
ReumaClinic Genk
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Vanhoof, MD
Facility Name
OLV Aalst
City
Aalst
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9300
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tom Zwaenepoel, MD
Facility Name
RZ Heilig Hart
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veerle Taelman, MD
Facility Name
University Hospitals Leuven (UZ Leuven)
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Verschueren, MD, PhD
First Name & Middle Initial & Last Name & Degree
Johan Joly, MSc
First Name & Middle Initial & Last Name & Degree
Elias De Meyst, MD
Facility Name
Cliniques Universitaires Saint-Luc Bruxelles
City
Brussel
ZIP/Postal Code
1000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis
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