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

NCT06983821 | Recruiting Phase 3 DMC

• 1 other identifier: 20250118-01T
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Microscopic Polyangiitis (MPA); Granulomatosis With Polyangiitis

Keywords

ANCA-associated vasculitis; cyclophosphamide; glucoccorticoid; rituximab; vasculitis; granulomatosis with polyangiitis; microscopic polyangiitis; GPA; MPA

Outcome Measures

Primary Outcomes (2)

• Pilot trial: percent adherence to intervention regimen

  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)

  12 weeks

• Full-scale trial: Rate of serious infection

  Full-scale trial: rate of serious infection (Infection occurring after randomisation requiring IV antibiotics, or leading to hospitalisation or death)

  26 weeks

Secondary Outcomes (2)

• Pilot trial: recruitment rate

  52 weeks

• Full-scale trial: Remission rate

  26 weeks

Other Outcomes (13)

• End-stage kidney disease rate

  26 and 52 weeks

• Change in eGFR

  26 and 52 weeks

• Death

  26 and 52 weeks

Study Arms (2)

Intervention Arm

EXPERIMENTAL

IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks

Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab (R)

Standard of care

ACTIVE COMPARATOR

Participants in this arm receive standard of care treatment induction agent and glucocorticoid dose/duration, left to the discretion of the investigator

Drug: Standard of Care (SOC)

Interventions

Standard of Care (SOC) DRUG

Participants will receive standard of care induction agent and glucocorticoid taper, at investigator discretion

Standard of care

Prednisone DRUG

4 weeks prednisone taper

Intervention Arm

Rituximab (R) DRUG

Rituximab infusions, dosing and schedule at clinician/investigator discretion

Intervention Arm

Cyclophosphamide DRUG

IV Cyclophosphamide 15mg/kg/dose (age and eGFR adjusted), 2 doses 2 weeks apart

Also known as: Cytoxan

Intervention Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• A diagnosis of vasculitis other than GPA or MPA (including eosinophilic granulomatosis with polyangiitis, IgA vasculitis, cryoglobulinemic vasculitis, rheumatoid vasculitis)
• Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
• A diagnosis of systemic lupus erythematosus or Sjögren's syndrome
• Receipt of dialysis for \>21 days immediately prior to randomization or prior renal transplant
• Age \<18
• Pregnant at time of screening
• Treatment with \>1 IV dose of CYC and/or \>14 days PO CYC and/or \>14 days of prednisone/prednisone (less than or equal to 30mg/day) and/or \>1 dose of RTX within the 28 days immediately prior to randomization
• Chronic viral infection: HIV. HBV or HCV
• Untreated latent mycobacterium tuberculosis infection
• Active infection at time of presentation
• A comorbidity or condition that, in the opinion of the investigator, precludes the use of GC, CYC or RTX

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (2)

St-Joseph's Hospital

Hamilton, Ontario, Canada

NOT YET RECRUITING

The Ottawa Hospital

Ottawa, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis

Interventions

Cyclophosphamide; Standard of Care; Prednisone; Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Massicotte-Azarniouch, MD, MSc

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Massicotte-Azarniouch, MD, MSc

CONTACT

613-738-8400; damassicotte@toh.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, randomised controlled trial

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: May 21, 2025
• Study Start: November 10, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)