BION-1301 for IgA Nephropathy

Recruiting at 200 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chinook Therapeutics, Inc.

Must be taking: ACEi, ARB, SGLT2i, ERAs

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Type 1 diabetes, Nephrotic syndrome, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

350 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of certain medications like ACE inhibitors, ARBs, SGLT2 inhibitors, ERAs, and MRAs if you are already taking them. However, you cannot use systemic corticosteroids or immunosuppressant medications during the trial.

What evidence supports the effectiveness of the drug BION-1301 for IgA Nephropathy?

Research shows that targeting APRIL, a protein involved in the disease process of IgA Nephropathy, can reduce harmful immune responses in the kidneys. Anti-APRIL therapies, like BION-1301, have been shown to lower levels of problematic proteins and improve kidney function in animal studies and early human trials. ^{1 2 3 4 5}

Is BION-1301 safe for humans?

Preliminary results from studies on anti-APRIL therapies, including BION-1301 (also known as zigakibart and sibeprenlimab), suggest that these treatments are generally well-tolerated in humans. Further studies are ongoing to confirm their safety. ^{1 2 3 4 5}

What makes the drug BION-1301 unique for treating IgA nephropathy?

BION-1301 is unique because it is an anti-APRIL monoclonal antibody, which targets a specific protein involved in the disease process of IgA nephropathy, potentially offering a novel approach compared to traditional treatments like corticosteroids and renin-angiotensin system blockers. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing BION-1301, a new medication, in adults with IgA nephropathy. The goal is to see if it can help reduce the amount of protein leaking into their urine by improving kidney function.

Eligibility Criteria

Adults over 18 with IgA Nephropathy, weighing at least 50 kg, can join this trial. They must agree to use contraception and follow the study's procedures. People using immunosuppressants, with severe allergies to monoclonal antibodies, diabetic complications, or a history of Type 1 Diabetes cannot participate.

Inclusion Criteria

I weigh at least 50 kg.

I agree to use birth control as directed and follow the study's requirements.

Exclusion Criteria

I have a history of diabetes-related blood vessel problems and my diabetes medication isn't stable.

I have been diagnosed with Type 1 Diabetes.

I am taking medication that weakens my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 600 mg BION-1301 or placebo subcutaneously every 2 weeks for 104 weeks

104 weeks

Bi-weekly visits, some may be remote

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 weeks

Treatment Details

Interventions

• BION-1301
• Placebo

Trial Overview The trial is testing BION-1301 for safety and effectiveness in treating IgA Nephropathy compared to a placebo (a substance with no active drug). Participants will be randomly assigned to receive either BION-1301 or the placebo.

Participant Groups

Group I: BION-1301 Experimental Treatment 1 Intervention

600mg subcutaneous administration every 2 weeks for 104 weeks

Group II: Placebo Placebo Group 1 Intervention

subcutaneous administration every 2 weeks for 104 weeks

Who Is Running the Clinical Trial?

Chinook Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

APRIL is a key player in the development of immunoglobulin A nephropathy (IgAN), as it is linked to B-cell dysregulation and the overproduction of harmful IgA1, with higher levels correlating to more severe disease.

Anti-APRIL therapies have shown promise in reducing harmful IgA1 levels and improving kidney inflammation, with several new drugs currently being tested for their safety and effectiveness in treating IgAN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy. Yeo, SC., Barratt, J.[2023]

APRIL plays a crucial role in the regulation of B cells and is implicated in the development of IgA nephropathy (IgAN), the most common primary glomerulonephritis, which can lead to severe kidney disease.

Preliminary clinical trial data suggest that inhibiting APRIL may reduce proteinuria and slow kidney disease progression in IgAN, prompting the development of several anti-APRIL drug candidates currently in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence. Mathur, M., Chan, TM., Oh, KH., et al.[2023]

In a phase 2 trial involving 155 adults with IgA nephropathy, treatment with sibeprenlimab for 12 months led to a significant reduction in proteinuria compared to placebo, with reductions of 47.2% to 62.0% depending on the dosage.

The safety profile of sibeprenlimab was comparable to placebo, with adverse event rates of 78.6% in the treatment groups versus 71.1% in the placebo group, indicating that sibeprenlimab is a potentially safe option for patients at high risk of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. Mathur, M., Barratt, J., Chacko, B., et al.[2023]

The study confirms that APRIL plays a pathogenic role in IgA nephropathy (IgAN) and demonstrates that neutralizing APRIL with a monoclonal antibody (4540) effectively reduces harmful immune responses in a mouse model, leading to lower serum IgA levels and kidney deposits of IgA, IgG, and C3.

The humanized antibody VIS649 showed promising results in non-human primates, achieving up to a 70% reduction in serum IgA levels and a decrease in specific B cell populations, suggesting its potential as a safe and effective treatment for IgAN in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Myette, JR., Kano, T., Suzuki, H., et al.[2020]

VIS649 (sibeprenlimab) was found to be safe and well tolerated in a phase 1 study involving 51 healthy adults, with no serious adverse events reported, indicating a favorable safety profile for further development.

The drug effectively suppressed APRIL and various immunoglobulins in a dose-dependent manner, while still allowing for a normal immune response to a tetanus/diphtheria vaccine, suggesting it may be a promising treatment for IgA nephropathy without compromising vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Mathur, M., Barratt, J., Suzuki, Y., et al.[2022]

Patients with IgA nephropathy (IgAN) showed a significantly reduced immune response to nasal immunization with cholera toxin subunit B (CTB), indicating a defect in their mucosal IgA immune response compared to healthy controls.

The study suggests that while IgAN patients have a compromised initial immune response to mucosal antigens, they may still develop a hyperresponsive immune reaction upon subsequent parenteral immunization, highlighting the need for more frequent antigen exposure to establish effective mucosal immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy. de Fijter, JW., Eijgenraam, JW., Braam, CA., et al.[2019]

The study developed two monoclonal antibodies that specifically recognize hypo-galactosylated immunoglobulin A1 (HG-IgA1), which is significantly elevated in patients with IgA nephropathy (IgAN) compared to healthy controls and patients with other kidney diseases.

These antibodies showed strong binding to serum IgA from IgAN patients, indicating their potential as a reliable tool for screening and diagnosing IgAN, based on a study involving 49 IgAN patients, 48 patients with other kidney diseases, and 41 healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specificity of two monoclonal antibodies against a synthetic glycopeptide, an analogue to the hypo-galactosylated IgA1 hinge region. Hiki, Y., Hori, H., Yamamoto, K., et al.[2021]

In a study involving 28 patients with IgA nephropathy (IgAN), 26 patients with non-immunological renal disease, and 32 healthy subjects, oral immunization with Salmonella typhi Ty21a significantly increased IgM, IgG, IgA, IgA1, and IgA2 responses across all groups, indicating a robust immune response.

However, IgAN patients exhibited a significantly lower IgA1 response in plasma compared to controls, suggesting a hyporesponsiveness that may require more frequent exposure to IgA1-inducing antigens for effective mucosal immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy. Roodnat, JI., de Fijter, JW., van Kooten, C., et al.[2019]

In a study of 464 patients with immunoglobulin A nephropathy (IgAN) after kidney transplantation, the use of single-agent renin-angiotensin-aldosterone system blockade (RAASB) was linked to a reduction in albuminuria, which is a key indicator of kidney health.

Patients using single beta blockers or calcium channel blockers had a significantly worse prognosis compared to those on RAASB, suggesting that RAASB may improve graft survival in early IgAN cases by lowering albumin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: a retrospective cohort study. Park, S., Baek, CH., Go, H., et al.[2023]

Recent studies indicate that corticosteroids may be effective in treating IgA nephropathy (IgAN) in patients with lower estimated glomerular filtration rates (eGFR), but they also carry a higher risk of adverse events.

The STOP-IgAN trial suggests that while corticosteroids can reduce proteinuria, their impact on renal function remains unclear, and the TESTING trial shows that corticosteroids can decrease the risk of renal function decline but also increase the risk of side effects, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the treatment of IgA nephropathy. Barbour, S., Feehally, J.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence. [2023]

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

A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. [2023]

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

A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. [2020]

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

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. [2022]

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

Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Specificity of two monoclonal antibodies against a synthetic glycopeptide, an analogue to the hypo-galactosylated IgA1 hinge region. [2021]

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

Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: a retrospective cohort study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

An update on the treatment of IgA nephropathy. [2022]