REDO study: Research into the effects of lower doses rituximab in patients with rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2016-002908-15-NL
• Date of registration: 23/08/2016
• Prospective Registration: Yes
• Primary sponsor: Sint Maartenskliniek
• Public title: REDO study: Research into the effects of lower doses rituximab in patients with rheumatoid arthritis
• Scientific title: REDO study: RhEumatoid arthritis REtreatment with ultra-low dose Rituximab: Disease Outcome after Dose Optimization - REDO
• Date of first enrolment: 08/11/2016
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002908-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Usual dose of rituximab (1x1000mg); Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Junior researcher
• Affiliation: Sint Maartenskliniek

• Name: Junior researcher
• Affiliation: Sint Maartenskliniek

Key inclusion & exclusion criteria

Inclusion criteria:
- Rheumatoid arthritis: either 2010 ACR RA and/or 1987 RA criteria and/or clinical diagnosis of the treating rheumatologist, fulfilled at any time point between start of the disease and inclusion.

- RTX retreatment: at least once RTX in the last 18 months for RA in a dose of 1 × 1000 mg, 2 × 1000 mg or 2 × 500 mg and no other biologicals received after last RTX dose. Patients treated with innovator RTX (MabThera) as well as registered biosimilars will be included.

- At least 6 months of stable, low disease activity after the last RTX infusion (operationalized by either DAS28-CRP<2.9 (DAS28-BSE <3.2) or judgement of low disease activity by a rheumatologist) AND a current DAS28-CRP =3.5.

- Patient informed consent, =18 years old and mentally competent

- Ability to measure the outcome of the study in this patient (e.g. life expectancy > 6 months, no planned relocation out of reach of study centre)

- Ability to read and communicate well in Dutch

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
- Patients with known (non-)response to ultra-low dose RTX (below 1 × 1000 mg)

- Current corticosteroid dosing above 10 mg per day prednisolone equivalent



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid arthritis
MedDRA version: 19.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: MabThera
Pharmaceutical Form: Infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7

Primary Outcome(s)

Main Objective: To assess the difference in efficacy between two ultra-low doses (1 x 200 mg and 1 x 500 mg) and standard low dose (1 x 1000 mg) of rituximab retreatment on the change in DAS28-CRP, compared to a pre-specified non-inferiority margin of 0.6, at 3 and 6 months in patients with RA previously treated with RTX using a conventional dose

Secondary Objective: - To assess the difference in efficacy between the two ultra-low dose interventions

- To compare the proportion of patients with low disease activity or remission and remission according to Boolean ACR/EULAR criteria of all groups

- To assess the difference in the change from baseline in functioning between all groups.

- To assess the difference in change from baseline in quality of life between all groups.

- To assess the safety of each dose of RTX

- To assess the difference in medication use between all groups.

- To assess whether baseline factors are predictive for obtaining DAS28-CRP low disease activity state at 6 months.

- To estimate the cost effectiveness of both ultra-low RTX doses compared to the conventional low dose over the 6 months study period.

- To compare the course of serum (anti-)RTX levels between all groups.

Primary end point(s): Change in DAS28-CRP from baseline

Timepoint(s) of evaluation of this end point: - 3 months follow-up
- 6 months follow-up

Secondary Outcome(s)

Secondary end point(s): - Disease activity (DAS28-CRP (TJC, SJC, CRP, VAS global patient), VAS global rheumatologist, VAS pain, ESR, OMERACT flare questionnaire)
- Function (HAQ-DI)
- Quality of life (EQ5D)
- Adverse events
- Medication use
- Pharmacokinetics (RTX and anti-RTX levels)
- Pharmacodynamics (serum free light chains, S100)

Timepoint(s) of evaluation of this end point: Baseline, 3 and 6 months follow-up

Secondary ID(s)

RR-152-REDO

Source(s) of Monetary Support

Menzis

CZ

Ethics review

Status: Approved
Approval date:
Contact: