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Avacopan Added to Standard-of-care Therapy in ANCA-associated Vasculitis With Severe Kidney Involvement

NCT07373262 · Status: NOT_YET_RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 130

Last updated 2026-01-28

No results posted yet for this study

Summary

ANCA-associated vasculitis (AAV) is a rare auto-immune disease, with high mortality in the absence of treatment. There is still an unmet need to define new treatment strategies to reduce drug side effects, as well as to reverse rare cases of refractory AAV and improve the kidney response to improve the long-term outcomes.

Severe forms of AAV-related necrotizing and crescentic rapidly progressive glomerulonephritis (RPGN) (i.e. estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m²) are associated with higher mortality, higher incidence of infections, and long-term consequences including chronic kidney disease (CKD) with subsequent complications (end-stage kidney disease (ESKD) requiring dialysis, cardiovascular diseases) and a burden of financial costs.

In patients with AAV and RPGN, recent guidelines recommend using a standard-of-care (SOC) immunosuppressive regimen including an induction regimen (rituximab or cyclophosphamide), plus glucocorticoids (GCs) (starting at 60 mg/day and tapering over 6-12 months) (+ or - plasma exchanges).

Since GCs also participate to the long-term control of AAV, new molecular pathophysiology-driven therapeutic approaches rapidly blocking and/or reversing AAV lesions are needed to go beyond the progressive control of AAV using GCs alone. Thus, an add-on approach including GCs-based immunosuppressive regimen plus a new targeted therapy may lead to both AAV control (systemic disease) and improvement of the kidney outcome (organ involvement).

Avacopan a selective inhibitor of the C5a receptor, recently emerged as a new therapeutic option in AAV. In a phase 3 comparative study (that included a small subset of patients with eGFR 15-29 mL/min/1.7m2), avacopan was superior to glucocorticoids taper with respect to sustained remission at week 52. In the avacopan arm, the cumulative dose of GCs was dramatically reduced and avacopan was thus proposed as an alternative to GCs rather to a synergic treatment. In the subgroup of patients with eGFR \<30 mL/min/1.73m², avacopan was associated with a better eGFR gain at week 52 compared to prednisone, but data in this population at-risk of worse kidney outcomes are scarce, and did not include patients with eGFR \< 15 mL/min/1.73m², those patients being excluded from the study.

In the REVERSE study, investigators put forward the hypothesis that avacopan added on GCs regimen may significantly improve the kidney outcome of severe AAV (synergic approach), and thus improve short- and long-term global outcomes (survival, cardiovascular status). REVERSE will thus compare GCs-based SOC + placebo to GCs-based SOC + avacopan.

Conditions

  • ANCA-Associated Vasculitis (AAV)

Interventions

DRUG

Avacopan

At day 0, and weeks 4, 8, 12, 20 36 patients will have avacopan dispensation

DRUG

Placebo

At day 0, and weeks 4, 8, 12, 20 36 patients will have placebo dispensation

Sponsors & Collaborators

  • University Hospital, Toulouse

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
85 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-03-01
Primary Completion
2030-03-01
Completion
2030-07-01

Countries

  • France

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07373262 on ClinicalTrials.gov