Low-Dose Glucocorticoid Therapy for ANCA Vasculitis

(SAFE-LOW Trial)

Not yet recruiting at 1 trial location

Overseen By David Massicotte-Azarniouch, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Hospital Research Institute

Must not be taking: CYC, Prednisone, RTX

Disqualifiers: Other vasculitis, Lupus, Sjögren's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new, low-dose steroid treatment for individuals with ANCA-associated vasculitis, a condition where the immune system attacks blood vessels, often affecting the kidneys. It compares a short, four-week course of prednisone (a type of glucocorticoid) combined with other medications to the usual treatment. Suitable candidates for this trial have been newly diagnosed with, or are experiencing a relapse of, granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) and have severe kidney issues related to the disease. The trial aims to determine if this new treatment is safe and effective compared to standard care. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in care.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using a combination of IV cyclophosphamide, rituximab, and prednisone to treat ANCA-associated vasculitis is generally safe. Studies have found that up to 90% of patients experience significant improvement in their symptoms, known as remission. However, some risks exist. About 10% to 20% of patients may face serious complications or even death within five years of treatment. These complications often include infections that might require hospitalization.

Most people handle the treatments well, but it's important to be aware of the potential for serious side effects. Prospective participants should discuss these risks with their healthcare provider before joining a clinical trial for this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ANCA vasculitis?

Researchers are excited about the low-dose glucocorticoid therapy for ANCA vasculitis because it offers a potentially safer way to manage this condition compared to standard high-dose glucocorticoids, which often come with significant side effects. Unlike traditional treatments that primarily rely on high doses of prednisone, this approach uses a reduced dosage alongside IV cyclophosphamide and rituximab, aiming to maintain effectiveness while minimizing adverse effects. This combination could lead to better patient outcomes by reducing long-term steroid exposure, which is a significant concern with current treatment methods.

What evidence suggests that this trial's treatments could be effective for ANCA vasculitis?

In this trial, participants in the intervention arm will receive a treatment combining IV cyclophosphamide, rituximab, and prednisone. Research has shown this combination to be very effective for ANCA-associated vasculitis, a condition where the immune system attacks blood vessels. Studies indicate that about 94% of patients experience remission within six months, and around 90% continue to have no symptoms at 12 months. With success rates ranging from 80% to 96%, this treatment is a strong option for effectively managing ANCA vasculitis symptoms. ^{2 3 4 6 7}

Who Is on the Research Team?

David Massicotte-Azarniouch, MD, MSc

Principal Investigator

The Ottawa Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with ANCA-associated vasculitis, including conditions like Microscopic Polyangiitis and Granulomatosis with Polyangiitis. Participants should have severe kidney involvement. The study will assess if they can safely receive a lower dose of glucocorticoids alongside usual treatments.

Inclusion Criteria

I tested positive for specific autoimmune markers.

My kidney biopsy shows specific types of damage or my urine test shows signs of kidney disease.

My kidney function is severely impaired due to active AAV, with an eGFR less than 40.

Exclusion Criteria

I have been diagnosed with lupus or Sjögren's syndrome.

Pregnant at time of screening

I have a chronic viral infection (HIV, HBV, or HCV).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of IV Cyclophosphamide, Rituximab, and 4 weeks of Prednisone

4 weeks

Pilot Follow-up

Participants are monitored for adherence to the intervention regimen

12 weeks

Full-scale Follow-up

Participants are monitored for serious infections and remission status

26 weeks

Extended Follow-up

Participants are monitored for long-term outcomes such as end-stage kidney disease and glucocorticoid exposure

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Prednisone

Trial Overview The SAFE-LOW trial is testing the safety and effectiveness of a low-dose glucocorticoid therapy given for 4 weeks in combination with standard induction agents (Rituximab or Cyclophosphamide) compared to the current higher-dose standard care in patients with severe kidney disease from vasculitis.

How Is the Trial Designed?

Group I: Intervention Arm Experimental Treatment 3 Interventions

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

Group II: Standard of care Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6322443/

Long-term follow-up of a combined rituximab and ... A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2780489

Effect of Reduced-Dose vs High-Dose Glucocorticoids ... Although those therapies have high remission rates of 80% to 90%, mortality at 5 years is still high at 10% to 20%.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925001378

Long-Term Follow-Up of a Glucocorticoid Minimizing ... At 12 months, 90% of patients were in sustained remission. A case-control analysis of matched patients enrolled in previous European Vasculitis Society trials ...

4. kireports.org kireports.org/article/S2468-0249(25)00255-4/fulltext

Combination Cyclophosphamide and Rituximab to ... Disease Outcomes. One hundred seven patients (96%) achieved treatment-induced disease remission (median time-to-remission 77 [IQR: 64–92] ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0909169

Rituximab versus Cyclophosphamide in ANCA-Associated ... Treatment with rituximab has led to remission rates of 80 to 90% among patients with refractory ANCA-associated vasculitis and may be safer than ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12436411/

Safety and Effectiveness of Combination Rituximab and ... The primary outcomes of interest were death and infection requiring hospitalization within 12 months of combination therapy. Secondary outcomes ...

7. rmdopen.bmj.com rmdopen.bmj.com/content/11/4/e005743

Efficacy and safety of avacopan for treatment of patients ... Remission at week 26 and sustained remission at week 52 were achieved by 37/59 (62.7%) and 33/59 (55.9%) patients in the avacopan group and 34/ ...