Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
134
Countries
1
Sites
12
Rheumatoid arthritis
The main objective of this open label multicenter randomised controlled pragmatic superiority trial is to investigate the optimal treatment/tapering strategy with rituximab for patients with rheumatoid arthritis with a goal of reducing disease impact.
Key facts
- Sponsor
- UZ Leuven
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 9 Jan 2024 → ongoing
- Decision date (initial)
- 2023-11-28
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Fonds voor Wetenschappelijk Reumaonderzoek (FWRO) · Celltrion Healthcare · UZ Leuven (Fonds academische studies)
External identifiers
- EU CT number
- 2023-506638-59-01
- ClinicalTrials.gov
- NCT06003283
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The main objective of this open label multicenter randomised controlled pragmatic superiority trial is to investigate the optimal treatment/tapering strategy with rituximab for patients with rheumatoid arthritis with a goal of reducing disease impact.
Secondary objectives 1
- The main secondary objective is to investigate the optimal treatment/tapering strategy with rituximab for patients with rheumatoid arthritis to reduce disease activity.
Conditions and MedDRA coding
Rheumatoid arthritis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10039073 | Rheumatoid arthritis | 100000004859 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Whole trial duration (2 years) Patients will be 1:1 randomised to the experimental arm or the active comparator arm.
|
Randomised Controlled | None | Active comparator arm: interval prolongation: Arm in which rituximab will be administrated in a fixed dose of 1 x 1000 mg intravenously (IV) based on interval prolongation (treatment according to the current Belgian reimbursement criteria for retreatment with rituximab: retreatment in case of a relapse of rheumatoid arthritis with a Disease Activity Score in 28 joints (DAS28) ≥3.2 and last administration of rituximab at least 24 weeks before). Experimental arm: disease activity guided dose reduction: Arm in which patients taper rituximab based on disease activity-guided dose reduction. Patients in this arm will receive rituximab at fixed intervals of 24 weeks, and the administered dose of rituximab will be reduced in case of a Disease Activity Score in 28 joints (DAS28) ≤3.2 according to the following sequence: 1 x 1000 mg intravenously (IV) (maximum), 1 x 500 mg IV, 1 x 200 mg IV (minimum). In case of a DAS28 score >3.2, the last effective dose will be administered. |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-506638-59-00 | Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-Guided Dose Reduction in Patients with Rheumatoid Arthritis: The RITUXERA Trial. | UZ Leuven |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- 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 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 7
- Current treatment with a biological disease modifying antirheumatic drug (bDMARD) other than rituximab.
- Current treatment with a targeted synthetic DMARD.
- Pregnancy or pregnancy wish.
- Hypersensitivity to rituximab or to its excipients.
- Active severe infection.
- Severe immune deficiency.
- Severe heart failure (New York Heart Association (NYHA) Class IV) or other severe uncontrolled cardiac condition.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Comparison between both study arms of disease impact (Rheumatoid Arthritis Impact of Disease (RAID) questionnaire) over 104 weeks.
Secondary endpoints 11
- Comparison between both study arms of disease activity (AUC of the Disease Activity Score in 28-joints - C-reactive Protein (DAS28-CRP)) over 104 weeks.
- Cumulative dose of rituximab in the two trial arms over 104 weeks.
- Cumulative dose of glucocorticoids in the two trial arms over 104 weeks.
- Disease activity (AUC of the Simplified Disease Activity Index (SDAI)) in the two study arms over 104 weeks.
- Maintenance of disease control (DAS28-CRP ≤3.2) in both study arms.
- Rituximab drug retention rate in both study arms.
- Proportion of patients achieving a good/moderate European League Against Rheumatism (EULAR) response 12 weeks after treatment with rituximab in both study arms.
- Proportion of patients who tapered the dose of rituximab below 1 x 1000 mg IV in the experimental arm.
- Mean/median interval between administrations of rituximab in the active control arm.
- Proportion of patients with serious adverse events/reactions in both study arms.
- Proportion of patients with serious infections in both study arms.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 8
Rixathon 100 mg concentrate for solution for infusion
PRD6641095 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/17/1185/001
- MA holder
- SANDOZ GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Truxima 500 mg concentrate for solution for infusion
PRD4797331 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/16/1167/001
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
MabThera 100 mg concentrate for solution for infusion
PRD2154041 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Ruxience 500 mg concentrate for solution for infusion
PRD7980794 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/20/1431/002
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
MabThera 500 mg concentrate for solution for infusion
PRD2154043 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Truxima 100 mg concentrate for solution for infusion
PRD5065907 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/16/1167/002
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Ruxience 100 mg concentrate for solution for infusion
PRD7980793 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/20/1431/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Rixathon 500 mg concentrate for solution for infusion
PRD6060651 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000.00 mg milligram(s)
- Max total dose
- 5000.00 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/17/1185/004
- MA holder
- SANDOZ GMBH
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
UZ Leuven
- Sponsor organisation
- UZ Leuven
- Address
- Herestraat 49
- City
- Leuven
- Postcode
- 3000
- Country
- Belgium
Scientific contact point
- Organisation
- UZ Leuven
- Contact name
- Patrick.Verschueren
Public contact point
- Organisation
- UZ Leuven
- Contact name
- Patrick.Verschueren
Locations
1 EU/EEA country · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 134 | 12 |
| Rest of world | — | 0 | — |
Investigational sites
Reumacentrum Genk
Rheumatology, Weg naar As 123, 3600, Genk
AZ St.-Elisabeth Herentals VZW
Rheumatology, Nederrij 133, 2200, Herentals
Universitair Ziekenhuis Antwerpen
Rheumatology, Drie Eikenstraat 655, 2650, Edegem
Cliniques Universitaires Saint-Luc
Rheumatology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Reumaclinic
Rheumatology, Jaarbeurslaan 21/22, 3600, Genk
Ziekenhuis Aan De Stroom
Rheumatology, Lange Bremstraat 70, 2170, Antwerp
Imelda
Rheumatology, Imeldalaan 9, 2820, Bonheiden
UZ Leuven
Rheumatology, Herestraat 49, 3000, Leuven
Algemeen Ziekenhuis Delta
Rheumatology, Deltalaan 1, 8800, Roeselare
UZ Brussel
Rheumatology, Laarbeeklaan 101, 1090, Jette
Regionaal Ziekenhuis Heilig Hart Leuven
Rheumatology, Naamsestraat 105, 3000, Leuven
Azorg
Rheumatology, Moorselbaan 164, 9300, Aalst
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2024-01-09 | 2024-01-09 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 30 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-506638-59-01 Public Version | 5.0 |
| Protocol (for publication) | D4 _Patient facing documents_HAQ-DI_FR | 1 |
| Protocol (for publication) | D4 _Patient facing documents_WPAI_FR | 1 |
| Protocol (for publication) | D4_Patient facing documents_ASES_FR | 1 |
| Protocol (for publication) | D4_Patient facing documents_ASES_NL | 1 |
| Protocol (for publication) | D4_Patient facing documents_EQ5D_FR | 1 |
| Protocol (for publication) | D4_Patient facing documents_EQ5D_NL | 1 |
| Protocol (for publication) | D4_Patient facing documents_HAQ-DI_NL | 1 |
| Protocol (for publication) | D4_Patient facing documents_RAID_FR | 1 |
| Protocol (for publication) | D4_Patient facing documents_RAID_NL | 1 |
| Protocol (for publication) | D4_Patient facing documents_VAS patient_FR | 1 |
| Protocol (for publication) | D4_Patient facing documents_VAS patient_NL | 1 |
| Protocol (for publication) | D4_Patient facing documents_WPAI_NL | 1 |
| Protocol (for publication) | Protocol signature RITUXERA | 2.0 |
| Protocol (for publication) | Protocol signature RITUXERA CUSL public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA Heilig Hart Leuven public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA OLV Aalst public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA Reumacentrum Genk public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA ReumaClinic Genk public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA UZ Leuven public version | 1.8 |
| Protocol (for publication) | Protocol signature RITUXERA ZNA Jan Palfijn public version | 1.8 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_2023-506638-59-01_Public Version | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_2023-506638-59-01_FR_Public version | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_2023-506638-59-01_NL_Public version | 4.0 |
| Subject information and informed consent form (for publication) | L2_Sponsor statement on use of ICF model for interventional trials with IMP on adult patients_Public | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Mabthera_EN | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Rixathon_EN | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ruxience_EN | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Truxima_EN | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EN-NL-FR-DE 2023-506638-59-01 Public Version | 5.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-09-07 | Belgium | Acceptable 2023-11-28
|
2023-11-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-12 | Belgium | Acceptable 2024-08-19
|
2024-08-19 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-06-10 | Belgium | Acceptable 2025-08-04
|
2025-08-27 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-05-13 | Belgium | Acceptable 2025-08-04
|
2026-05-13 |