Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis (SATELITE)
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|ClinicalTrials.gov Identifier: NCT04871191|
Recruitment Status : Not yet recruiting
First Posted : May 4, 2021
Last Update Posted : June 8, 2022
|Condition or disease||Intervention/treatment||Phase|
|Granulomatosis With Polyangiitis Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis||Drug: Rituximab Drug: Tocilizumab Drug: Abatacept||Phase 2|
Granulomatosis with polyangiitis (GPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV).
Combination of glucocorticoids and either cyclophosphamide or rituximab is the standard of care for remission-induction of new-onset organ-threatening or life-threatening GPA. Few patients fail to respond to both cyclophosphamide and rituximab, but it is not uncommon for patients to have persistent disease activity resulting in inability to taper glucocorticoids, which is also considered refractory disease. The current recommendations for patients with GPA refractory to remission-induction therapy are to switch from cyclophosphamide to rituximab or from rituximab to cyclophosphamide. However, there are no recommendations for the management of patients with inadequate response after both treatments. Treatment with a biologic disease-modifying antirheumatic drugs (DMARD) or a combination of rituximab and a cDMARD are potential treatments options but have not been properly evaluated in such cases. Among biologic DMARD that have been evaluated in AAV, some have shown promising results, including tocilizumab and abatacept.
Identifying the most promising therapeutic strategy for patients with GPA and inadequate response to standard of care therapy may improve management of GPA.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Salvage Therapy for Patients With Inadequate Response to Standard of Care Therapy in Granulomatosis With Polyangiitis|
|Estimated Study Start Date :||September 2022|
|Estimated Primary Completion Date :||February 2026|
|Estimated Study Completion Date :||June 2026|
Active Comparator: Rituximab + cDMARD
Rituximab will be administered at 375 mg/m²/week for four consecutive weeks. Maintenance rituximab at a fixed dose of 500 mg will be administered at week 24 and at week 52. The choice of the cDMARD will be left to the treating clinician and will include either methotrexate, azathioprine or mycophenolate mofetil, but the choice will be preferably methotrexate. Methotrexate will be administered orally or subcutaneously at 0.3 mg/kg/week, azathioprine orally at 2-3 mg/kg/d and mycophenolate mofetil orally at 2-3 g/d.
375 mg/m²/week for four consecutive weeks (Week 0, 1, 2 and 3) Maintenance rituximab at a fixed dose of 500 mg will be administered at week 24 and at week 52.
Other Name: Mabthera
Tocilizumab will be administered subcutaneously every week at a fixed dose of 162 mg per week.
Subcutaneous injection of 162 mg per week
Other Name: RoActemra
Abatacept will be administered subcutaneously every week at a fixed dose of 125 mg per week.
Subcutaneous injection of 125 mg per week
Other Name: Orencia
- Proportion of patients with a response or a remission [ Time Frame: week 12 ]defined according to the EULAR recommendations. Remission is defined as the absence of disease activity attributable to active disease qualified by the need for ongoing stable maintenance immunosuppressive therapy. The term ''active disease'' is not restricted to vasculitis only, but also includes other inflammatory features like granulomatous inflammation. Response is defined as a 50% reduction of disease activity score and absence of new manifestations.
- Proportion of patients with a response or a remission at week 26 and 52. [ Time Frame: week 26 and 52 ]according to the EULAR recommendations
- Physician's and patient's global assessment of disease activity [ Time Frame: week 12 and 52 ]The difference between the physician's and patient's global assessment of disease activity between baseline and week 12 and between baseline and week 52 using a scale ranging from 0 to 100, with higher scores indicating more activity.
- Patient-reported outcomes [ Time Frame: week 12, 24 and 52 ]The patient-reported outcomes (PRO) including the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire, a 29-item profile measure comprising six domains, with higher scores meaning more active disease, at week 12, 24, and 52 after randomization, and during the long-term follow-up.
- Adverse events [ Time Frame: week 26 and 52 ]The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at week 26 and 52 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions
- Corticosteroids use [ Time Frame: week 26 and 52 ]The area under the curve for corticosteroids at week 26 and 52
- Vasculitis Damage Index [ Time Frame: week 26 and 52 ]The Vasculitis Damage Index (VDI, scoring from 0 to 58, higher scores indicating more damage) at week 26 and 52
- Health Assessment Questionnaire (HAQ) [ Time Frame: week 26 and 52 ]ranging from 0 to 3, with higher scores indicating worse functional impairment
- Short Form 36 (SF-36) Health questionnaire [ Time Frame: week 26 and 52 ]scores range from 0 to 100 for each component, with lower scores indicating greater impairment of quality of life
- ANCA titers [ Time Frame: week 26 and 52 ]Evolution of ANCA titers in the treatment groups
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04871191
|Contact: Jonathan London, MD||+33 1 44 64 16 firstname.lastname@example.org|
|Contact: Audrey Beclin-Clabaux||+331 58 41 33 email@example.com|
|Hôpital de la Croix Saint Simon|
|Paris, France, 75020|
|Contact: Jonathan London, MD + 33 1 44 64 16 02 firstname.lastname@example.org|
|Study Director:||Benjamin Terrier, MD, PhD||AP-HP - Service médecine interne|