Avacopan for IgA Nephropathy

Recruiting at 1 trial location

Overseen By Nicholas Geroux

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

Trial Summary

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.

What data supports the effectiveness of the drug Avacopan for IgA Nephropathy?

Research shows that treatments involving corticosteroids like methylprednisolone and prednisolone can help improve outcomes in IgA nephropathy by reducing kidney damage and protein in the urine. While Avacopan is not directly studied here, its use alongside these drugs may offer similar benefits. ^{1 2 3 4 5}

Is Avacopan (Tavneos) safe for humans?

The safety data for methylprednisolone (a related corticosteroid) shows that it can cause serious complications if used incorrectly, such as retinal and conjunctival damage when injected improperly. However, when used correctly, it is generally safe for conditions like rheumatoid arthritis, though it may have side effects like any medication. ^{6 7 8 9 10}

How is the drug Avacopan different from other drugs for IgA nephropathy?

Avacopan is unique because it targets a specific part of the immune system called the complement pathway, which is different from traditional treatments like corticosteroids that broadly suppress the immune system. This targeted approach may offer benefits in reducing inflammation with potentially fewer side effects. ^{1 2 5 11 12}

What is the purpose of this trial?

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.

Research Team

Fernando C. Fervenza, MD, PhD

Principal Investigator

Mayo Clinic, Rochester, MN

Nabeel Aslam, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of methylprednisolone, cyclophosphamide in pediatric IgA nephropathy assessed by renal biopsy. [2022]

2. Chile pubmed.ncbi.nlm.nih.gov

[Rapidly progressing glomerulonephritis secondary to IgA nephropathy. A clinical case]. [2010]

3. England pubmed.ncbi.nlm.nih.gov

Disappearance of glomerular IgA deposits in childhood IgA nephropathy showing diffuse mesangial proliferation after 2 years of combination/prednisolone therapy. [2017]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Steroid treatment for severe childhood IgA nephropathy: a randomized, controlled trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. [2014]

7. Germany pubmed.ncbi.nlm.nih.gov

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. [2021]

9. India pubmed.ncbi.nlm.nih.gov

Conjunctival Necrosis due to Subconjunctival Methylprednisolone (Depo-Medrol™) Acetate Injection. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. [2014]

11. United States pubmed.ncbi.nlm.nih.gov

In IgA nephropathy, oral methylprednisolone reduced adverse kidney outcomes but increased adverse events. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Advances in treatment: immunoglobulin A nephropathy. [2007]