TARPEYO® for Immunoglobulin A Nephropathy

(NefXtend Trial)

Recruiting at 11 trial locations

Overseen By Kristin Önnestam

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Calliditas Therapeutics AB

Must be taking: TARPEYO, RAS inhibitors

Must not be taking: Systemic immunosuppressives, CYP3A4 inhibitors

Disqualifiers: Other glomerulopathies, Nephrotic syndrome, Dialysis, 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: 15 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of renin-angiotensin system (RAS) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors if they are already taking them. However, you cannot take systemic immunosuppressive medications other than TARPEYO® during the trial.

What data supports the effectiveness of the drug TARPEYO® for treating Immunoglobulin A Nephropathy?

Budesonide (Tarpeyo) has been approved to reduce proteinuria (excess protein in urine) in adults with primary immunoglobulin A nephropathy, indicating its effectiveness in managing this condition. ^{1 2 3 4 5}

Is TARPEYO® (budesonide) safe for humans?

TARPEYO® (budesonide) can suppress the immune system, which may increase the risk of infections. Patients should be cautious and avoid contact with people who have infections. ^{5 6 7 8 9}

How is the drug TARPEYO® unique in treating IgA nephropathy?

TARPEYO® (budesonide) is unique because it specifically targets and reduces proteinuria (excess protein in urine) in adults with IgA nephropathy, also known as Berger's disease. Unlike other treatments, it works by suppressing the immune system, which can increase the risk of infections, so patients need to be cautious about exposure to infections. ^{3 4 5 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to assess the efficacy and safety of extended TARPEYO® (delayed-release budesonide capsules) treatment in adult patients with primary IgA nephropathy who have completed 9 months of TARPEYO® 16 mg once daily treatment in real-world clinical practice. The main question it aims to answer is: Is there a treatment benefit of TARPEYO® 16 mg QD extended use? Participants will * take part in this study for about 19 months * Have urine tests done * Have blood samples taken * Have physical examinations done

Research Team

Kristin Önnestam

Principal Investigator

Calliditas Therapeutics

Eligibility Criteria

Adults diagnosed with primary IgA nephropathy (kidney disease) who have already completed 9 months of TARPEYO® treatment. They must have consistent proteinuria, be on a stable dose of certain medications for kidney function and diabetes, and have access to their past lab results.

Inclusion Criteria

I have medical records of my condition from the last 3 months before starting TARPEYO®.

I can provide past lab results for kidney function tests.

My recent tests show protein in my urine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TARPEYO® 16 mg QD for 6 months followed by TARPEYO® 8 mg QD for 9 months

15 months

Regular visits for urine tests, blood samples, and physical examinations

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a 2-week tapering period with TARPEYO® 4 mg QD

3 months

Treatment Details

Interventions

• TARPEYO®

Trial Overview The trial is testing the benefits and safety of continuing TARPEYO® (delayed-release budesonide capsules) beyond 9 months in adults with IgA nephropathy. It involves urine tests, blood samples, physical exams over approximately 19 months.

Participant Groups

Group I: 16 mg QD then 8 mg QD Experimental Treatment 1 Intervention

6-months of TARPEYO® 16 mg QD then 9-month Treatment Period with TARPEYO® 8 mg QD and TARPEYO®4 mg QD for 2 weeks for tapering.

Who Is Running the Clinical Trial?

Calliditas Therapeutics AB

Lead Sponsor

Trials

11

Recruited

1,200+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

In a study of 132 IgA nephropathy patients with chronic kidney disease, low-dose corticosteroids combined with oral cyclophosphamide significantly reduced the risk of severe kidney decline compared to uncontrolled supportive care, suggesting a more effective treatment option.

The combination therapy also resulted in better renal survival rates and lower proteinuria levels, with no significant increase in hospitalization for infections, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide. Ma, F., Yang, X., Zhou, M., et al.[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]

IgA nephropathy is a common autoimmune kidney disease that can lead to kidney failure, and current treatment options mainly focus on reducing proteinuria through non-specific methods like renin-angiotensin blockade.

There is a significant need for new therapies for IgA nephropathy, as existing treatments, including immunosuppressive agents, are limited and primarily target inflammation rather than the underlying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating IgA nephropathy: quid novi? Hartono, C., Muthukumar, T.[2021]

In a study of 60 patients with early-stage IgA nephropathy, treatment with ramipril did not significantly improve outcomes compared to no treatment over a 5-year period, with similar rates of hypertension and proteinuria between groups.

While ramipril was well tolerated overall, the study found no significant benefits in renal function or event-free survival, suggesting that this treatment may not be necessary for patients with minimal proteinuria and normal renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of early immunoglobulin A nephropathy by angiotensin-converting enzyme inhibitor. Li, PK., Kwan, BC., Chow, KM., et al.[2013]

Budesonide (Tarpeyo) has been approved to help reduce proteinuria in adults with primary immunoglobulin A nephropathy, indicating its efficacy in managing this kidney condition.

Patients using budesonide should be monitored for potential drug-drug interactions and advised about the increased risk of infections due to its immunosuppressive effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Drug to Reduce Proteinuria in Berger's Disease. Aschenbrenner, DS.[2023]

In a study using Tsukamoto-French alcoholic rats, 67% of the rats developed IgA nephropathy after 6 to 10 weeks of continuous alcohol exposure, while none of the control rats showed this condition, indicating a strong link between alcohol abuse and kidney damage.

The findings revealed renal changes similar to those seen in humans, including mesangial expansion and IgA deposition, suggesting that this rat model effectively mimics the effects of chronic alcohol consumption on kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgA nephropathy in alcohol abuse. An animal model. Smith, SM., Yu, GS., Tsukamoto, H.[2007]

In a study of 107 patients with IgA nephropathy followed for an average of 6.6 years, the angiotensinogen-M235T genetic polymorphism was linked to the presence of nephrotic syndrome and influenced the deterioration of renal function.

The combination of angiotensinogen-M235T and ACE-I/D polymorphisms showed a synergistic effect on disease progression, suggesting that these genetic markers could be important for predicting outcomes in IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy. Bantis, C., Ivens, K., Kreusser, W., et al.[2007]

In a study involving 82 rats, those that ingested alcohol continuously developed IgA nephropathy, with 60% affected at 6 weeks and 100% by 16 weeks, indicating a strong link between prolonged alcohol consumption and kidney disease.

In contrast, control rats that received a glucose-based diet showed no signs of IgA nephropathy, highlighting the specific impact of alcohol on kidney health in this animal model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time dependency of IgA nephropathy induction in alcohol ingestion. Smith, SM., Tsukamoto, H.[2019]

A patient developed crescentic IgA nephropathy after receiving recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for liver cancer, marking the first documented case of this kidney condition linked to these treatments.

The patient's renal function improved partially and stabilized after stopping rIL2 and LAK therapy, along with plasmapheresis and steroid treatment, suggesting that IL2 may play a role in causing kidney injury in IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver. Chan, TM., Cheng, IK., Wong, KL., et al.[2018]

Eculizumab, an anti-C5 medication, was effective in stabilizing renal function and reducing proteinuria in an adolescent with rapidly progressive IgA nephropathy, despite prior immunosuppressive treatments.

The treatment's benefits were temporary, indicating that early initiation of eculizumab may be crucial in managing progressive IgA nephropathy by targeting complement-mediated inflammation in the kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab treatment for rescue of renal function in IgA nephropathy. Rosenblad, T., Rebetz, J., Johansson, M., et al.[2022]

IgA nephropathy is a common form of chronic kidney disease that presents significant challenges in understanding its causes and treatment options.

There are promising opportunities for developing new tests and treatments that could help manage and control IgA nephropathy more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgA nephropathy: challenges and opportunities. Glassock, RJ.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide. [2021]

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

Advances in treatment: immunoglobulin A nephropathy. [2007]

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

Treating IgA nephropathy: quid novi? [2021]

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

Treatment of early immunoglobulin A nephropathy by angiotensin-converting enzyme inhibitor. [2013]

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

First Drug to Reduce Proteinuria in Berger's Disease. [2023]

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

IgA nephropathy in alcohol abuse. An animal model. [2007]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy. [2007]

8. England pubmed.ncbi.nlm.nih.gov

Time dependency of IgA nephropathy induction in alcohol ingestion. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Eculizumab treatment for rescue of renal function in IgA nephropathy. [2022]

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

IgA nephropathy: challenges and opportunities. [2019]