Evaluation of 200 mg of Rituximab every 6 months as maintenance treatment of Rituximab-treated patients with rheumatoid arthritis: a non-inferiority prospective randomised controlled trial (RADAR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Jun 2025 → ongoing

Decision date (initial)

2025-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519991-18-00

ClinicalTrials.gov

NCT06906549

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response

The primary objective is to show the non-inferiority of the 200mg dose of rituximab compared to the standard 1g dose on disease activity, as measured by mean DAS28-CRP between the first infusion and 12 months afterward, in patients treated with rituximab for rheumatoid arthritis.

Secondary objectives 13

1. To compare the disease activity measured by DAS28-CRP between the two arms at day 0, 6 months and 12 months
2. To compare the disease activity status (low disease activity, DAS-remission, Boolean remission) between the two arms at day 0, 6 months and 12 months
3. To compare treatment failure
4. To compare occurrence of disease flares
5. To compare the patient disability index
6. To compare the patient quality of life
7. To compare B, T and NK cell subpopulations
8. To compare change in IgG, IgA and IgM levels
9. To compare vaccine response
10. To compare Human antichimeric antibody (HACAs) levels
11. To monitor humoral immunosuppression by the measurement of Torque Teno Virus in the serum.
12. To compare infections and serious infections
13. To compare adverse events and serious adverse events

Conditions and MedDRA coding

Rheumatoid Arthritis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 years
2. Diagnosis of rheumatoid arthritis (RA) according to EULAR/ACR 2010 classification criteria
3. DAS28 ≤ 5.1
4. Current maintenance treatment with Rituximab regardless of dose and/or duration of Rituximab treatment and with at least first cycle of Rituximab ended (2 initial infusions)
5. Last Rituximab infusion between 6 and 18 months prior to day 0
6. Corticosteroids ≤10 mg/day within 4 weeks prior to day 0
7. Affiliation to a social insurance system or beneficiary
8. Written informed consent to participate in the study, dated and signed before starting the trial
9. Effective method of birth control during the study

Exclusion criteria 13

1. Rheumatic autoimmune disease other than RA (except associated Sjogren’s disease, which is allowed)
2. Concurrent treatment with any other targeted therapy than Rituximab
3. Any contraindication to Rituximab or to NaCl 0.9%
4. Significant uncontrolled associated disease or comorbidity
5. Known active infection or history of serious recurrent or chronic infection
6. Laboratory findings: active or untreated latent tuberculosis, hepatitis B positive, hepatitis C positive, haemoglobin <8 g/dL, neutropenia < 1.5G/L or IgG <5 g/L
7. Pregnancy (women of childbearing potential : positive urinary pregnancy test at the inclusion visit), breastfeeding, or planned pregnancy during the study (on subject declaration)
8. Drug addiction, alcohol addiction
9. Patients who cannot be followed for the 12 month-duration
10. Patients over the age of legal majority who are protected, or deprived of liberty by judicial or administrative decision
11. Subject in exclusion period (determined by a previous or ongoing study)
12. Patients unable to give informed consent (e.g., patients in a situation of medical emergency, patients who have difficulty comprehending the essential details of the trial...)
13. Patients who have difficulty reading or understanding French, or who have an inability to understand the delivered information

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean reduction of rheumatoid arthritis activity score (DAS28-CRP) between day 0 and 12 months to show non-inferiority of the lower dose.

Secondary endpoints 13

1. DAS28-CRP at day 0, 6 months and 12 months
2. DAS28 categories : Remission: DAS28 < 2.6 ; Low Disease Activity: 2.6 ≤ DAS28 ≤ 3.2 ; Moderate Activity: 3.2 < DAS28 ≤ 5.1; High Disease Activity: DAS28 > 5.1 ; Boolean Remission Criteria defined as tender joint count (TJC) ≤ 1, swollen joint count (SJC) ≤ 1, CRP (mg/dL) ≤ 1, Patient global assessment (on a 0–10 scale) ≤ 1 at day 0, 6 months and 12 months
3. Number of Rituximab infusions, number of patients switching or initiating a cDMARD or switching from Rituximab to another bDMARD, number of patients using oral corticosteroids at a dose greater than 10 mg/day throughout study period
4. Number of flares throughout study period, FLARE questionnaire at 6 and 12 months
5. RAPID-3 score and RAID at day 0, 6 months and 12 months
6. EQ5D-5L and SF-36 at day 0, 6 months and 12 months
7. B, T and NK cell phenotyping at day 0, 6 months and 12 months
8. IgG, IgA and IgM at day 0, 6 months and 12 months
9. Vaccinal serologies at day 0, 6 months and 12 months (Diphteria, pneumococcus, tetanus and Haemophilus influenzae type B)
10. HACA at day 0 and 12 months
11. Evolution of Torque Teno Virus (TTV) viral load in the serum of patients between day 0 and 12 months
12. Number of infections and serious infections
13. Number of adverse events and serious adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Eden SEBBAG

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Eden SEBBAG

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications