BION-1301 for IgA Nephropathy

Recruiting at 28 trial locations

Overseen By Aamir Jamal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Ace inhibitors, Arbs

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Alcohol, Drugs, Pregnancy, others

Compensation: Varies

Number of Visits: Unknown

103 Participants Needed

Trial Summary

What is the purpose of this trial?

Multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BION-1301 in healthy volunteers and adults with IgA Nephropathy (IgAN).

Will I have to stop taking my current medications?

The trial requires that participants with IgA Nephropathy be stable on their current dose of ACE inhibitors or ARBs for at least 3 months before joining. However, if you are taking systemic corticosteroids or other immunosuppressive therapies, you must stop these at least 3 months before starting the trial.

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

Research shows that targeting APRIL, a protein involved in IgA nephropathy, with antibodies like BION-1301 can reduce harmful immune responses in the kidneys. Studies in animals and early human trials suggest that blocking APRIL can lower protein levels in urine and slow kidney damage. ^{1 2 3 4 5}

Is BION-1301 safe for humans?

Preliminary results from studies on anti-APRIL therapies, including those similar to BION-1301, suggest they are generally well-tolerated in humans, with ongoing research to confirm their safety. ^{1 2 3 4 6}

How is 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 immune response, potentially reducing the production of IgA antibodies that contribute to kidney damage in IgA Nephropathy. This mechanism is different from other treatments that may not specifically target this pathway. ^{7 8 9 10 11}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults with IgA Nephropathy (IgAN) who have had a kidney biopsy in the last 10 years, protein in urine, and stable kidney function. They must be non-smokers, not pregnant or breastfeeding, not using drugs or alcohol excessively, and agree to use contraception. Healthy volunteers aged 18-55 with a BMI of 18-35 kg/m^2 can also participate.

Inclusion Criteria

I have not smoked or used nicotine products for at least 3 months.

I agree to follow the study's rules for birth control for 6 months after the last dose.

I am 18 years old or older.

Exclusion Criteria

I do not have any major health issues that could make this study unsafe for me.

Participated in any other study in which receipt of an investigational new drug, or investigational device occurred within 28 days, or 5 half-lives (whichever is longer) of first dose of study drug in the present study

You have regularly consumed alcohol, used marijuana in the last 3 months, or used hard drugs like cocaine and phencyclidine in the last year. If a blood or urine test shows that you have used drugs or alcohol, you may be excluded from the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Single Ascending Dose (SAD)

Double-blind, randomized, placebo-controlled, single ascending dose in healthy volunteers

4-6 weeks

Part 2: Multiple Ascending Dose (MAD)

Double-blind, randomized, placebo-controlled, multiple ascending dose in healthy volunteers

8-12 weeks

Part 3: Multiple Dose (MD)

Open-label, multiple dose in participants with IgA Nephropathy

12-16 weeks

Part 4: Retreatment

Eligible participants from Part 3 may enroll for optional retreatment due to disease progression or by choice

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BION-1301

Trial Overview The trial is testing BION-1301's safety and effects on the body compared to a placebo. It involves giving either one dose or multiple doses of BION-1301/placebo to see how it's tolerated by healthy people and those with IgAN.

Participant Groups

Group I: Part 4 Retreatment: BION-1301 Experimental Treatment 1 Intervention

Eligible participants from Part 3 may enroll in Part 4 due to disease progression or by choice for optional retreatment and receive SC injection at 600mg/biweekly.

Group II: Part 3: BION-1301 Experimental Treatment 1 Intervention

Two cohorts of participants will receive multiple doses of BION-1301 by IV infusion (Cohort 1) or SC injection (Cohort 2) at 600mg/biweekly.

Group III: Part 2: BION-1301 Experimental Treatment 1 Intervention

Up to 4 cohorts with multiple doses of BION-1301 administered by intravenous (IV) infusion.

Group IV: Part 1: BION-1301 Experimental Treatment 1 Intervention

Up to 5 cohorts with single ascending doses of BION-1301 administered by intravenous (IV) infusion.

Group V: Part 1: Placebo Placebo Group 1 Intervention

Participants will receive a single dose of placebo administered by IV infusion.

Group VI: Part 2: Placebo Placebo Group 1 Intervention

Participants will receive placebo by IV infusion.

Who Is Running the Clinical Trial?

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

Chinook Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Findings from Research

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]

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]

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]

In a study of eight patients with idiopathic membranous nephropathy (IMN), treatment with the anti-CD20 antibody rituximab led to a significant reduction in proteinuria, with levels decreasing by 66% after 12 months, indicating effective disease management.

Rituximab was found to be safe, with no major drug-related side effects reported, and it resulted in sustained disease remission, suggesting a more favorable long-term risk/benefit profile compared to traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in idiopathic membranous nephropathy: a one-year prospective study. Ruggenenti, P., Chiurchiu, C., Brusegan, V., 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]

References

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

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

2. 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]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. [2022]

6. 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]

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

Rituximab in idiopathic membranous nephropathy: a one-year prospective study. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Study on the assay of proximal tubular antigen in urine and serum with an anti-human renal monoclonal antibody]. [2015]

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

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

10. 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]

11. Australia pubmed.ncbi.nlm.nih.gov

Detection of gender difference and epitope specificity of IgG antibody activity against IgA1 hinge portion in IgA nephropathy patients by using synthetic hinge peptide and glycopeptide probes. [2019]