Avacopan for IgA Nephropathy

Recruiting at 1 trial location

Overseen By Zach Monson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: RAS blockade

Must not be taking: Rituximab, MMF, CYC, AZA

Disqualifiers: Cancer, Infection, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Avacopan (also known as Tavneos), combined with low-dose glucocorticoids, for individuals with crescentic IgA nephropathy. Researchers aim to determine if this combination is safe and effective for those at high risk of disease progression. Suitable participants should have had this specific kidney condition confirmed by a biopsy within the last six months and be managing their blood pressure and protein intake. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have taken certain immunosuppressive drugs recently, and you must have been on RAS blockade for at least 4 weeks. If you are on an SGLT2 inhibitor, you can continue it at the same dose, but you cannot start or increase the dose during the trial.

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

Research has shown that Avacopan is generally safe and well-tolerated by patients. Studies have not identified any major safety concerns that would hinder further research on Avacopan, making it a promising option for potential trial participants.

Glucocorticoid treatments like Methylprednisolone, Prednisolone, and Prednisone are commonly used medications. They can cause side effects, especially at higher doses, such as an increased risk of infections and changes in mood or weight. However, doctors are well-equipped to manage these known side effects.

Overall, both Avacopan and glucocorticoid treatments have demonstrated a reasonable safety profile in past studies, which is encouraging for those considering participation in the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Avacopan for IgA Nephropathy because it offers a novel approach compared to standard treatments like high-dose steroids. Unlike typical glucocorticoids, Avacopan targets the complement system, specifically the C5a receptor, helping to reduce inflammation without the broad immune suppression associated with steroids. This targeted mechanism could lead to fewer side effects and improve patient quality of life. Additionally, Avacopan is taken orally, which is more convenient compared to intravenous treatments. Overall, this treatment holds promise for being a more precise and user-friendly option for managing IgA Nephropathy.

What evidence suggests that this trial's treatments could be effective for IgA Nephropathy?

This trial will compare Avacopan combined with low-dose glucocorticoids to high-dose glucocorticoids for treating IgA Nephropathy. Research has shown that Avacopan, when used with low-dose steroids, may help treat IgA Nephropathy, a kidney disease. In a short-term study, about 50% of patients with this condition experienced significant improvement in their urine protein levels, indicating better kidney health. Another study on a similar condition found that only 10.1% of patients taking Avacopan experienced a relapse, compared to 21% of those not taking it. This suggests Avacopan might reduce the chances of the disease returning. Overall, these results are promising for people with high-risk IgA Nephropathy. ^{1 2 3 4 6}

Who Is on the Research Team?

Fernando C. Fervenza, MD, PhD

Principal Investigator

Mayo Clinic, Rochester, MN

Nabeel Aslam, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with a severe form of kidney disease known as crescentic IgA Nephropathy, which has a high risk of getting worse. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and may be excluded based on factors like other medical conditions or treatments that could interfere with the study.

Inclusion Criteria

My kidney biopsy shows a specific type of kidney disease.

I am older than 18 years.

Hematuria defined as >10 RBC/hpf or hemoglobinuria >1+

Exclusion Criteria

My kidney biopsy shows severe damage.

I am not pregnant or breastfeeding.

My kidney disease is related to another health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avacopan and low-dose glucocorticoid or high-dose glucocorticoid for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avacopan
• Methylprednisolone
• Prednisolone
• Prednisone

Trial Overview The trial is testing the effectiveness and safety of Avacopan when used alongside low doses of glucocorticoids (steroid medications) in treating crescentic IgA Nephropathy. The comparison might involve standard treatments such as Prednisone, Methylprednisolone, or Prednisolone.

How Is the Trial Designed?

Group I: Avacopan and Low Doses Glucocorticoid Active Control 3 Interventions

* 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

Group II: High Doses Glucocorticoid Active Control 2 Interventions

* 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)

Avacopan is already approved in United States for the following indications:

Approved in United States as Tavneos for:

• ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

A case of conjunctival necrosis occurred in an 82-year-old patient after an inadvertent subconjunctival injection of methylprednisolone following cataract surgery, highlighting a serious complication associated with this medication.

Methylprednisolone is not approved for use in the eye, and this incident underscores the risks of using unapproved medications in ophthalmic procedures, emphasizing the need for caution and adherence to approved treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjunctival Necrosis due to Subconjunctival Methylprednisolone (Depo-Medrol™) Acetate Injection. van Zyl, LM., Hill, JJ.[2021]

Corticosteroids and fish oil capsules have shown the most promise as treatment options for patients with IgA nephropathy, based on recent publications.

A multicenter, placebo-controlled study is underway to evaluate the effectiveness of alternate-day prednisone and highly purified fish oil concentrate in children and young adults with moderately severe IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in treatment: immunoglobulin A nephropathy. Hogg, RJ., Waldo, B.[2007]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

In a study involving eight elderly patients with rheumatoid arthritis, oral administration of methylprednisolone showed a relative bioavailability of 69.2%, indicating it is effectively absorbed when taken by mouth.

Both oral and intravenous (i.v.) routes of administration resulted in similar clinical responses, suggesting that oral methylprednisolone is a convenient alternative to i.v. therapy without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response. Hayball, PJ., Cosh, DG., Ahern, MJ., et al.[2019]

In a study of 15 patients previously diagnosed with corticosteroid-induced arachnoiditis, only 3 exhibited the clinical symptoms of arachnoiditis, suggesting a low incidence of the condition among those affected.

The findings indicate that the severity of radiological changes did not correlate with the severity of symptoms, leading to the conclusion that methylprednisolone acetate (Depo-Medrol) should be avoided in procedures involving the thecal sac due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. Johnson, A., Ryan, MD., Roche, J.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9050557/

C5a receptor inhibitor avacopan in immunoglobulin A ... This short-term pilot study showed an improvement in the slope of the UPCR, with ∼50% improvement in three of seven patients with IgAN.

2. tavneospro.com tavneospro.com/results/efficacy

Efficacy | TAVNEOS® (avacopan) 10.1% of patients in the TAVNEOS ® arm experienced a relapse, compared with 21% of patients in the Active Control arm2. Risk of relapse data. Efficacy2.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06676579

Study Details | NCT06676579 | Avacopan in Crescentic ... 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 ...

4. kidneymedicinejournal.org kidneymedicinejournal.org/article/S2590-0595(25)00114-1/fulltext

IgA Nephropathy: An Overview of the Clinical Trials From the final list of eligible studies, we extracted data on interventions, study design, primary endpoints, and trial status. Results. We ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923016157

Novel Treatment Paradigms: Primary IgA Nephropathy Results from part A of the study (N = 199) demonstrated a 27% reduction in mean urine protein-to-creatinine ratio and preservation of kidney function (3.87 ml/ ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20574867

Avacopan in Crescentic IgAN - Mayo Clinic 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 ...