Non-inferiority of Reduced-dose Rituximab in Rheumatoid Arthritis in Low Disease Activity and Remission (REDOREM)

Randomized, Prospective, Active-comparator Controlled, Patient-blinded Study to Demonstrate Non-inferiority of Reduced-dose Rituximab in Rheumatoid Arthritis Patients in Low Disease Activity and Remission - the REDOREM Study

To investigate whether a reduced-dose dosing regimen (1x500mg semiannually) of rituximab (RTX) (Mabthera®) is non-inferior in patients with rheumatoid arthritis (RA) whose disease is in persistent low disease activity (LDA) or clinical remission (REM) (pLDA/pREM) as compared to the standard dosing regimen of 1x1000mg semi-annual infusions.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis; Remission
• Intervention / Treatment: Drug: 500mg RTX Group; Drug: 1000mg RTX Group

Detailed Description

Randomized, controlled, single-centre study with 1x500mg or 1x1000 semi-annual infusions of RTX (Mabthera) as intervention and a follow-up period of 2 years. Patients as well as assessors will be blinded to the type of treatment. Patients in the 1x500mg group who experience a flare as defined by the disease activity score 28-ESR (DAS28) will receive 1x1000mg RTX (Mabthera) at their upcoming scheduled infusion appointment. Patients in the 1x1000mg group whose disease activity reaches DAS28 >3.2 during the duration of the study will be re-evaluated for a change in biological therapy and will discontinue the study.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of RA according to the 2010 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria
• Current treatment with RTX (at time of inclusion have already received at least 2 cycles of 1000mg RTX) at the Day-Clinic of the Division of Rheumatology of the Medical University of Vienna
• Persistent low disease activity or clinical remission as defined below
• Persistent clinical remission (pREM) will be defined as a simplified disease activity index (CDAI) (12) ≤2.8 measured at two time-points 6 months apart. The CDAI is calculated as follows: tender joint count (TJC) + swollen joint count (SJC) + patient's assessment of general health on a 100 mm visual analogue scale (GH) + evaluator's assessment of general health on a 100 mm visual analogue scale (EGH)
• Persistent low disease activity (pLDA) will be defined as a CDAI ≤10 measured at two timepoints 6 months apart Patients who achieve REM at only either one of the two successive time-points will be considered as having pLDA with regard to the current trial

Exclusion Criteria:

• Patients ≤ 18 yrs
• Patients receiving RTX for a disease other than RA
• Patients who fail to meet criteria for REM or LDA at either one of the two successive timepoints (i.e. having a disease activity >10 as measured by the clinical disease activity index, (CDAI))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 500mg RTX Group; Patients in this group will receive 1x500mg (500mg RTX group) RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24	Drug: 500mg RTX Group; Patients will receive 1x500mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24; Other Names: Mabthera 500mg
Active Comparator: 1000mg RTX group; Patients in this group will receive 1x1000mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24	Drug: 1000mg RTX Group; Patients will receive 1x1000mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24; Other Names: Mabthera 1000mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression	Sharp modified van der Heijde (SvdH) score, Scale 0 (best) - 488 (worse)	month 12
Radiographic progression	Sharp modified van der Heijde (SvdH) score, Scale 0 (best) - 488 (worse)	month 24
Physical function	Health assessment questionnaire disability index (HAQ-DI), Scale 0 (best) - 3.0 worse	months 12
Physical function	Health assessment questionnaire disability index (HAQ-DI), Scale 0 (best) - 3.0 worse	months 24
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 21
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 18
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 15
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 12
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 9
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 6
Proportion of flare	Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse)	month 3

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2015-002156-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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