Avacopan Added to Standard-of-care Therapy in ANCA-associated Vasculitis With Severe Kidney Involvement
REVERSE
2 other identifiers
interventional
130
1 country
30
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Mar 2026
Typical duration for phase_3
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 23, 2025
CompletedFirst Posted
Study publicly available on registry
January 28, 2026
CompletedStudy Start
First participant enrolled
March 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2030
January 28, 2026
January 1, 2026
4 years
December 23, 2025
January 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Improvement in the kidney function
Proportion of patients reaching an estimated glomerular filtration rate \> or = 30 mL/min/1.7m² (CKD-EPI formula applied to the measure of standardized serum creatinine) at week 52 without requiring treatment study discontinuation for serious adverse event or treatment modification or intensification for refractory vasculitis or relapse.
Day 0 and 52 weeks after randomization
Secondary Outcomes (8)
Survival in both groups
Day 0, 52 and 64 weeks after randomization
Assessment of vasculitis activity
Day 0, 20, 52 and 64 weeks after randomization
Assessment of kidney function
Day 0, 20, 52 and 64 weeks after randomization
the proportion of end-stage kidney disease
Day 0, 20, 52 and 64 weeks after randomization
the evolution of the kidney inflammation
Day 0, 4, 12, and 52 weeks after randomization
- +3 more secondary outcomes
Study Arms (2)
GCs-based SOC + avacopan
EXPERIMENTALPatients will be standard of care (SOC and GCs) and receive Avacopan
GCs-based SOC + placebo
PLACEBO COMPARATORPatients will be standard of care (SOC and GCs) and receive placebo
Interventions
Eligibility Criteria
You may qualify if:
- Affiliated person or beneficiary of a social security scheme.
- Free, informed and written consent signed by the participant and the investigator
- For women able to procreate, ongoing effective contraception
You may not qualify if:
- Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol
- Treatment by \>3000 mg methylprednisolone or equivalent within the 3 weeks preceding the screening visit
- Known eGFR before the AAV flare already \<35 mL/min/1.73m2
- Pregnant or breast-feeding women, or desire to become pregnant within 24 months. All women of childbearing potential (WOCBP) are required to have a negative pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study and another 12 months after (or 12 months after the last rituximab infusion in case of premature termination): Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (Oral, Intravaginal, Transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (Oral, Injectable, Implantable); Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner.
- Hepatic dysfunction defined as:
- ALT,AST or alkaline phosphatase \> 3 ×ULN Total Bilirubin \>2 × ULN, with the exception of participants with Gilbert syndrome who may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN International normalized ratio (INR) \>1.7 (excepted if patient receive vitamin K antagonists)
- Co-administration of strong CYP3A4 enzyme inducers
- Known allergy to avacopan
- Other clinically active systemic autoimmune disease requiring therapy, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), moderate to severe systemic lupus erythematosus, IgA vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjögren's syndrome, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome or mixed connective tissue disease.
- Human immunodeficiency virus (HIV) positivity.
- Acute or chronic infection with hepatitis B (HBV) or hepatitis C (HCV).
- Positive serology for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) excludes the participant regardless of detection of hepatitis B surface antibodies (HBsAb) or HBV-DNA.
- Participants with a positive HCV antibody test should have HCV ribonucleic acid (RNA) levels measured. Participants with positive (detectable) HCV RNA must be excluded. Chronic hepatitis C participants, who have completed anti- HCV treatment for at least 12 weeks must have a negative HCV RNA result before randomization. Cases of spontaneous HCV clearance should be discussed with sponsor before enrolment.
- Active viral, bacterial or other infections requiring systemic treatment, or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
- Uncontrolled diabetes mellitus, lung diseases or any other illnesses not related to GPA/ MPA that in the opinion of the Investigator would jeopardize the ability of the patient to tolerate glucocorticoids
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
Amiens Hospital
Amiens, France
Angers Hospital
Angers, France
Besançon Hospital
Besançon, France
Bordeaux Hospital
Bordeaux, France
Boulogne-sur-Mer Hospital
Boulogne-sur-Mer, France
Brest Hospital
Brest, France
Caen Hospital
Caen, France
Grenoble Hospital
Grenoble, France
Vendée Hospital
La Roche-sur-Yon, France
Le Mans Hospital
Le Mans, France
Lille Hospital
Lille, France
Limoges Hospital
Limoges, France
Marseille Hospital
Marseille, France
Nantes Hospital
Nantes, France
Nimes Hospital
Nîmes, France
Bichat Hospital
Paris, France
Cochin Hospital
Paris, France
George Pompidou Hospital
Paris, France
Henri Mondor Hospital
Paris, France
Kremlin Bicêtre Hospital
Paris, France
Necker Hospital
Paris, France
Tenon Hospital
Paris, France
Reims Hospital
Reims, France
ROuen Hospital
Rouen, France
Strasbourg Hospital
Strasbourg, France
Saint exupery hospital
Toulouse, France
Toulouse Hospital
Toulouse, France
Tours Hospital
Tours, France
Valenciennes Hospital
Valenciennes, France
NANCY Hospital
Vandœuvre-lès-Nancy, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 23, 2025
First Posted
January 28, 2026
Study Start
March 1, 2026
Primary Completion (Estimated)
March 1, 2030
Study Completion (Estimated)
July 1, 2030
Last Updated
January 28, 2026
Record last verified: 2026-01