Avacopan in Crescentic Immunoglobulin A Nephropathy (IgAN)

October 1, 2025 updated by: Fernando Fervenza, Mayo Clinic

A Multi-Center, Phase II, Open Label, Randomized Trial Evaluating the Efficacy and Safety of Complement 5a Receptor Antagonist Avacopan in Crescentic IgA Nephropathy

The purpose of this study is to evaluate the efficacy and safety of Avacopan together with low-dose glucocorticoid in the treatment of patients with crescentic Imunoglobulin A Nephropathy (IgAN) and high risk of progression.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic in Florida
        • Principal Investigator:
          • Nabeel Aslam
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Fernando Custodio Fervenza

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Age > 18 years
  • Kidney biopsy showing crescentic IgA nephropathy within 6 months of enrolment (MEST-C-score =C1/C2).
  • Quantified creatinine clearance >20 ml/min/1.73m2
  • Quantified Proteinuria > 750 mg/24h based on a 24h urine collection while on maximum tolerated dose of RAS blockade
  • Hematuria defined as >10 RBC/hpf or hemoglobinuria >1+
  • Patients need to be in adequate supportive care (blood pressure <125/85mmHg, lifestyle advice, and maximum doses tolerable of RAS blockade) at least 4 weeks prior to enrollment
  • Patients would receive dietary and lifestyle counseling prior enrollment: low protein (0.8-1.0 g/kg/day) diet, low sodium (2 grams/day) intake, indication for smoke cessation, during the 4 weeks run-in period
  • Has signed an informed consent form prior to any study-related procedures
  • Patients with documented use of RAS blockade and adequate blood pressure control (<125/85 mmHg) for ≥4 weeks, can be enrolled in the study and randomized without repeating a 4-week run-in period.

Exclusion Criteria

  • Creatinine clearance <20 ml/min/1.73 m2
  • Liver function tests > 2x upper limit of normal. (Serious cases of hepatotoxicity have been reported in patients with avacopan during first approval and ADVOCATE study (29) (30)
  • Severe interstitial fibrosis and tubular atrophy (IFTA > 70% on renal biopsy)
  • Active cancer or acute non-controlled infection (including HIV, HBV, HCV)
  • Women who are pregnant or breastfeeding
  • Immunosuppression treatment:
  • Rituximab less than 12 months prior to enrollment
  • MMF, CYC, or immunomodulatory agents within 3 months prior to enrollment
  • AZA within 3 months prior to enrollment.
  • Glucocorticoids >20 mg/day within 1 month prior to enrollment
  • Secondary IgA nephropathy (associated with gastrointestinal diseases, infection, autoimmune, malignancy, respiratory tract, or skin)
  • ANCA-associated vasculitis or other vasculitis diagnostic defined by ACR criteria/Chapel Hill Consensus conference
  • Contraindication to use any of the protocol treatments (glucocorticoids, avacopan)
  • Use of a strong/moderate CYP3A4 inducer
  • Initiation of SGLT2 inhibitors is not allowed once patient has been enrolled in the study. Patients who have been on an SGLT2 inhibitor prior to enrollment on the study may continue on this therapy, at the same dose. No dose increase is allowed.
  • Active, untreated and/or uncontrolled chronic liver disease (chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis, cirrhosis
  • Unable to give written consent form
  • As a safety measure patients who are pregnant or lactating will not be enrolled in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Avacopan and Low Doses Glucocorticoid
  • Methylprednisolone 1g intravenous on day +1
  • Prednisone 0.2 mg/kg per day (maximum, 16 mg/day) for 2 months followed by dose tapering by 2 mg per day each month (total duration 6-9 months)
  • Avacopan 30 mg oral twice a day (1-0-1) for 12 months
Drug: Avacopan
Avacopan is a complement 5a receptor (C5aR) antagonist, orally active.
Other Names:
  • Tavneos
Drug: Methylprednisolone (drug)
Methylprednisolone 1g intravenous on day +1
Drug: Prednisolone
Prednisone 0.2 mg/kg per day (maximum, 16 mg/day) for 2 months followed by dose tapering by 2 mg per day each month (total duration 6-9 months)
Active Comparator: High Doses Glucocorticoid
  • Methylprednisolone 1g intravenous on day +1
  • Prednisone 0.4 mg/kg per day (maximum, 32 mg/day) for 2 months followed by dose tapering by 4 mg per day each month (total duration 6-9 months)
Drug: Methylprednisolone (drug)
Methylprednisolone 1g intravenous on day +1
Drug: Prednisone
0.4 mg/kg per day (maximum, 32 mg/day) for 2 months followed by dose tapering by 4 mg per day each month (total duration 6-9 months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in proteinuria measured by results of protein total, 24-hour urine collection at baseline compared to collection at 12 months.
Time Frame: 12 months
A response is based on the average of proteinuria quantified twice over a 2-weeks period at 12 months.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in proteinuria >50%
Time Frame: 12 months
This is based on the average of proteinuria quantified twice over a 2-weeks period at 12 months.
12 months
Change in eGFR (using 2021 CKD-EPI Formula)
Time Frame: 6 months, 12 months
• Change in eGFR (using 2021 CKD-EPI Formula) at 6 and 12 months compared to baseline
6 months, 12 months
Change in hematuria from Baseline to 12 month visit.
Time Frame: 12 months
Hematuria is measured in the urinalysis done at baseline and 12-month visit.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Fernando Fervenza, MD, Mayo Clinic, Rochester, MN
  • Principal Investigator: Nabeel Aslam, MD, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 9, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 2, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 2, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 3, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 24-005668

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings