Research into administration of lower dosed rituximab with an injection

Comparison of subcutaneous and intravenous continued treatment with ultra-low dose Rituximab in rheumatoid arthritis: a randomised open-label non-inferiority trial - RTX-SC

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-002507-19-NL

Enrollment

Registered

2020-09-03

Start date

2020-09-07

Completion date

Unknown

Last updated

2024-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

rheumatoid arthritis MedDRA version: 21.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Interventions

Trade Name: MabThera Product Name: rituximab Pharmaceutical Form: Solution for injection Trade Name: Rixathon Product Name: rituximab Pharmaceutical Form: Concentrate for solution for infusion

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Rheumatoid arthritis: either 2010 EULAR/ACR RA and/or 1987 ACR RA criteria and/or clinical diagnosis of the treating rheumatologist; 2. Patients using rituximab in ultra-low dose: either 200 mg or 500 mg as previous dose, given every 6 months, with or without concomitant methotrexate; 3. Having sufficient response to rituximab treatment, operationalized as a DAS28-CRP =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Previous non-response to ultra-low dose rituximab (DAS28-CRP > 2.9); 2. Objection or contraindication to either of the treatment options;

Design outcomes

Primary

Measure	Time frame
Main Objective: To investigate non-inferiority of rituximab SC 336 mg to rituximab IV 200 mg, with the lower boundary of the 95% confidence interval of AUC0-6mnd,SC : AUC0-6mnd,IV exceeding the non-inferiority margin of 0.8.;Secondary Objective: 1. To describe the relevant pharmacokinetic parameters of rituximab 336 mg SC compared to 200 mg IV: peak level, trough level, Cavg; 2. To evaluate the between group difference in changes in disease activity (DAS28-CRP) after 6 months, compared to a NI margin of 0.6; 3. To evaluate the between group differences on on B-cell counts; 4. To assess the differences in incidence of anti-drug antibodies (ADAs); 5. To assess the incidence of AEs in both groups; 6. To assess patient preferences for either SC or IV formulation. ;Primary end point(s): The main study endpoint is non-inferiority of rituximab 336 mg SC to rituximab 200 mg IV, based on AUC0-6 months. The AUC will be calculated using the four samples with the trapezoid method. ;Timepoint(s) of evaluation of this end point: Blood samples will be drawn pre-dose, post-dose (for IV directly after infusion, for SC 2-4 days after injection), at 3 months, and at 6 months.	—

Measure

Time frame

Main Objective: To investigate non-inferiority of rituximab SC 336 mg to rituximab IV 200 mg, with the lower boundary of the 95% confidence interval of AUC0-6mnd,SC : AUC0-6mnd,IV exceeding the non-inferiority margin of 0.8.;Secondary Objective: 1. To describe the relevant pharmacokinetic parameters of rituximab 336 mg SC compared to 200 mg IV: peak level, trough level, Cavg; 2. To evaluate the between group difference in changes in disease activity (DAS28-CRP) after 6 months, compared to a NI margin of 0.6; 3. To evaluate the between group differences on on B-cell counts; 4. To assess the differences in incidence of anti-drug antibodies (ADAs); 5. To assess the incidence of AEs in both groups; 6. To assess patient preferences for either SC or IV formulation. ;Primary end point(s): The main study endpoint is non-inferiority of rituximab 336 mg SC to rituximab 200 mg IV, based on AUC0-6 months. The AUC will be calculated using the four samples with the trapezoid method. ;Timepoint(s) of evaluation of this end point: Blood samples will be drawn pre-dose, post-dose (for IV directly after infusion, for SC 2-4 days after injection), at 3 months, and at 6 months.

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Secondary

Measure	Time frame
Secondary end point(s): Additional PK parameters In addition to the AUC0-6months, the peak level, the trough level and the average concentration (Cavg) are considered relevant PK parameters to compare both formulas. Those parameters will be calculated using (some of) the four RTX samples drawn, analysed by the RTX assay of Sanquin. Efficacy Disease activity will be measured at baseline, at three months and at six months, using the DAS28-CRP score. Therefore, we collect the following parameters: - Physical examination: swollen joint count, tender joint count; - Patient Global Assessment of disease activity (VAS); - Acute phase reactants: CRP. B-cell count B-cell count will be performed at baseline, at three months and at six months. For this analysis, blood will be drawn in a 3 ml EDTA tube. B-cell count will be performed at the Radboudumc immunology laboratory. The percentages and absolute number of B-cells will be determined within 24 hours after blood collection by using a combination of fluorochrome-labelled monoclonal antibodies, CD45, CD3, CD19 and CD16/56 (Tetra 2 combi from Beckman Coulter). With the use of a fully standardized volumetric counting flow cytometer, the Aquios (Beckman Coulter), samples will be incubated with MoAbs, erythrocytes will be lysed and subsequently the analysis will be automatically performed. Samples will be calibrated using standardized fixed cells samples (Aquios Immuno-Trol cells, Beckman Coulter). Quality control assessment is performed by participating in the regular program of the UK Neqas (Sheffield), the Alternative Immunomonitoring Program (12 samples per year). Anti-drug antibodies Presence of anti-drug antibodies against rituximab will be measured in the proportion of patients with undetectable rituximab levels. This means that in patients with rituximab levels < 0.1 mg/L anti-drug antibodies will be measured in serum. Samples will then be analysed using a validated ADA radio-immune assay at the bioanalytical laborator	—

Measure

Time frame

Secondary end point(s): Additional PK parameters In addition to the AUC0-6months, the peak level, the trough level and the average concentration (Cavg) are considered relevant PK parameters to compare both formulas. Those parameters will be calculated using (some of) the four RTX samples drawn, analysed by the RTX assay of Sanquin. Efficacy Disease activity will be measured at baseline, at three months and at six months, using the DAS28-CRP score. Therefore, we collect the following parameters: - Physical examination: swollen joint count, tender joint count; - Patient Global Assessment of disease activity (VAS); - Acute phase reactants: CRP. B-cell count B-cell count will be performed at baseline, at three months and at six months. For this analysis, blood will be drawn in a 3 ml EDTA tube. B-cell count will be performed at the Radboudumc immunology laboratory. The percentages and absolute number of B-cells will be determined within 24 hours after blood collection by using a combination of fluorochrome-labelled monoclonal antibodies, CD45, CD3, CD19 and CD16/56 (Tetra 2 combi from Beckman Coulter). With the use of a fully standardized volumetric counting flow cytometer, the Aquios (Beckman Coulter), samples will be incubated with MoAbs, erythrocytes will be lysed and subsequently the analysis will be automatically performed. Samples will be calibrated using standardized fixed cells samples (Aquios Immuno-Trol cells, Beckman Coulter). Quality control assessment is performed by participating in the regular program of the UK Neqas (Sheffield), the Alternative Immunomonitoring Program (12 samples per year). Anti-drug antibodies Presence of anti-drug antibodies against rituximab will be measured in the proportion of patients with undetectable rituximab levels. This means that in patients with rituximab levels < 0.1 mg/L anti-drug antibodies will be measured in serum. Samples will then be analysed using a validated ADA radio-immune assay at the bioanalytical laborator

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Countries

Netherlands

Contacts

Public ContactPrincipal investigator

Sint Maartenskliniek

a.denbroeder@maartenskliniek.nl

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026