Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW)

Phase 3

Not yet recruiting

• Conditions: Granulomatosis With Polyangiitis; Microscopic Polyangiitis (MPA)
• Interventions: Drug: Standard of Care (SOC); Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab (R)

• Registration Number: NCT06983821
• Lead Sponsor: Ottawa Hospital Research Institute

Brief Summary

The purpose of this study is to determine the safety and efficacy of a therapeutic regimen consisting of 4 weeks of glucocorticoids given with a combination of the usual induction agents for ANCA-associated vasculitis. The trial will compare this regimen to the current standard of care treatment and glucocorticoid dosing for ANCA-associated vasculitis with severe kidney involvement. This trial will begin as a pilot to assess feasibility of recruitment and of adherence to the intervention.

Detailed Description

ANCA-associated vasculitis (AAV) is an auto-immune disease which often involves the kidneys. It is a serious condition as it can lead to severe kidney impairment, often kidney failure, and may even be life-threatening. Current treatments, typically cyclophosphamide (CYC) or rituximab (RTX) with a tapering course of glucocorticoids (GC), allow most patients to achieve control of their disease (remission). Glucocorticoids are most often used initially at high doses, and then gradually decreased to low doses over at least 6 months. This leads to major treatment toxicities, notably infections and GC-related adverse events, major contributors to patient morbidity and mortality. Recent research has focused on finding ways to reduce treatment-related toxicities without compromising efficacy for controlling disease manifestations. This includes a reduced-dose GC taper for severe AAV from the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial, an even more reduced-dose GC taper in patients with moderate severity AAV from the Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis (LOVAS) trial, and a novel GC-sparing agent examined in the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) trial. Despite these advances, patients still experience high rates of infections, one of the major causes of death in the first year after diagnosis, particularly in patients with most severe forms of disease. Also, novel GC-sparing drugs are costly and have limited availability throughout the world; patients who cannot access this get exposed to significant amounts of GC and must suffer their dreaded side effects.

This study addresses the unresolved issues of unacceptably high infection risk and of providing a widely available means of reducing GC exposure to minimise treatment side effects. The investigators will examine an induction treatment regimen for severe AAV consisting of 2 doses of IV CYC in combination with 4 weeks of GC and standard RTX. The control arm will be the current standard of care treatment for severe AAV. Non-controlled studies suggest the use of short duration CYC with RTX allows for minimisation of up-front GC use, as little as 1-2 weeks, but this needs to be tested in a prospective, controlled manner. The investigators hypothesize that the combination of CYC with standard RTX will allow less GC to be used for AAV. This study will begin as a pilot to examine the feasibility of the conducting the study, adherence to the intervention regimen, and of recruiting patients. If feasibility is demonstrated, the study will be extended to a full-scale trial.

Study Timeline

• Study First Submitted: 2025-04-01
• Status Verified: 2025-05
• Study Start: 2025-05
• Study First Submitted QC: 2025-05-14
• Last Update Submitted: 2025-05-14
• Study First Posted: 2025-05-21
• Last Update Posted: 2025-05-21
• Primary Completion: 2028-02
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Arm	Prednisone	IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks
Intervention Arm	Rituximab (R)	IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks
Standard of care	Standard of Care (SOC)	Participants in this arm receive standard of care treatment induction agent and glucocorticoid dose/duration, left to the discretion of the investigator
Intervention Arm	Cyclophosphamide	IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks

Primary Outcome Measures

Name	Time	Method
Pilot trial: percent adherence to intervention regimen	12 weeks	Pilot trial: percent adherence in the intervention arm (non-adherence will be defined as the use of more than 25% of the total expected oral prednisone in the intervention arm at 12 weeks)
Full-scale trial: Rate of serious infection	26 weeks	Full-scale trial: rate of serious infection (Infection occurring after randomisation requiring IV antibiotics, or leading to hospitalisation or death)

Secondary Outcome Measures

Name	Time	Method
Pilot trial: recruitment rate	52 weeks	Pilot trial: recruitment rate measured as incidence rate based on randomised participants/centre-month
Full-scale trial: Remission rate	26 weeks	Full-scale trial: Remission defined as absence of manifestations due to active AAV. Remission status will be determined at study visits based on clinician judgement. If a participant is not in remission at an assessment point, the affected organ system (based on Birmingham Vasculitis Activity Score \[BVAS\]) will be captured. If a participant is transitioned to or being planned for maintenance therapy at their study visit, then they will also be considered to have achieved remission.

Trial Locations

Locations (2)

St-Joseph's Hospital; 🇨🇦 Hamilton, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada