Sibeprenlimab for IgA Nephropathy

Recruiting at 6 trial locations

Overseen By Otsuka Contact Center Otsuka Call Center

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Must not be taking: Systemic corticosteroids, Immunosuppression

Disqualifiers: Pregnancy, Chronic kidney disease, 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 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sibeprenlimab for individuals with IgA nephropathy, a kidney disease that can cause kidney damage. Researchers aim to evaluate how effectively sibeprenlimab alters specific disease markers. The trial seeks participants diagnosed with IgA nephropathy through a kidney biopsy and who meet a specific level of kidney function. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids or immunosuppressants within 24 weeks before starting the trial. Other forms of corticosteroids like topical or inhaled are allowed.

Is there any evidence suggesting that sibeprenlimab is likely to be safe for humans?

Research has shown that sibeprenlimab has promising safety results. Recent studies found it significantly reduced excess protein in urine over a year without major safety concerns. Although long-term safety is still under investigation, no serious side effects have been reported so far. This suggests sibeprenlimab is generally safe for patients with IgA nephropathy in the short to medium term. However, ongoing research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IgA nephropathy?

Sibeprenlimab is unique because it targets a specific protein involved in the progression of IgA nephropathy, which is different from many current treatments. Most treatments for this condition, like corticosteroids or immunosuppressants, focus on reducing inflammation broadly or suppressing the immune system. Sibeprenlimab, on the other hand, works by directly targeting the protein that contributes to kidney damage, potentially offering a more precise and effective approach with fewer side effects. Researchers are excited because this could lead to better outcomes for patients with a more targeted therapy.

What evidence suggests that sibeprenlimab might be an effective treatment for IgA nephropathy?

Research has shown that sibeprenlimab, the investigational treatment in this trial, may help treat IgA nephropathy, a kidney condition. In earlier studies, patients taking sibeprenlimab experienced a noticeable drop in protein levels in their urine, indicating reduced kidney damage. One study reported a 45.6% decrease in the protein-to-creatinine ratio in urine after nine months of treatment. Another study found a 51.2% reduction, which was both statistically and clinically significant. These findings suggest that sibeprenlimab could effectively lower urine protein levels, potentially protecting kidney function in people with IgA nephropathy. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals at least 16 years old with a confirmed diagnosis of IgA Nephropathy and a kidney function (eGFR) above 45 mL/min/1.73 m2. It's not for those with other chronic kidney diseases, low serum IgG levels, uncontrolled high blood pressure, pregnant or breastfeeding women, or anyone who has used systemic corticosteroids or immunosuppressants within the last 24 weeks.

Inclusion Criteria

Source-verified kidney biopsy confirmed diagnosis of IgAN

My kidney function, measured by eGFR, is above 45 mL/min/1.73 m2.

I am 16 years old or older.

Exclusion Criteria

Participant has a serum IgG value <600 mg/dL at screening

Participant has uncontrolled hypertension (defined as systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg)

I have chronic kidney disease not caused by IgA nephropathy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sibeprenlimab to evaluate its impact on kidney histopathology in IgAN

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sibeprenlimab

Trial Overview The trial studies Sibeprenlimab's effects on kidney tissue in patients with IgA Nephropathy. As an open-label phase 2b study, it aims to identify disease biomarkers and observe changes after treatment without hiding which participants receive the drug.

How Is the Trial Designed?

Group I: Sibeprenlimab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Published Research Related to This Trial

Dapagliflozin was found to be significantly more effective than placebo, immunosuppressants, and RAS blockade in preventing end-stage renal disease (ESRD) in IgA nephropathy patients, based on a review of 15 trials involving 1,983 participants.

In terms of safety, dapagliflozin demonstrated a lower risk of serious adverse events compared to glucocorticoids, making it a promising treatment option for patients at high risk of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness and safety for the treatments despite optimized renin-angiotensin system blockade among IgA nephropathy patients at high-risk of disease progression: A network meta-analysis of randomized controlled trials. Tan, Q., Xue, H., Ni, X., et al.[2023]

In a retrospective study of 18 patients with IgA Nephropathy (IgAN) treated with budesonide for 24 months, there was a significant median reduction in proteinuria of 45%, indicating its efficacy in managing this condition.

Budesonide treatment was well tolerated with minimal side effects, and it demonstrated a renal function decline similar to that of corticosteroids, suggesting it is a safe alternative for patients at high risk of progression in IgAN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison. Ismail, G., Obrişcă, B., Jurubiţă, R., et al.[2021]

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]

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]

Sibeprenlimab effectively reduces levels of the cytokine APRIL and immunoglobulin A (IgA) in a dose-dependent manner, with significant reductions observed at doses of 400 mg and 600 mg, indicating its potential efficacy in treating conditions like immunoglobulin A nephropathy.

The phase 1 study involving 48 healthy participants showed that sibeprenlimab was well-tolerated, with no serious adverse events reported, and demonstrated a favorable pharmacokinetic profile, with a mean elimination half-life of 8-10 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Sibeprenlimab in Healthy Participants. Zhang, X., Wang, Y., Yarbrough, J., et al.[2023]

A combination therapy of leflunomide (LEF) and prednisone showed a total efficacy rate of 60% in treating IgA nephropathy with nephrotic syndrome, which is comparable to the 65% efficacy rate of the control group receiving prednisone and MMF.

Both treatment regimens were well tolerated by patients, indicating that LEF is a safe option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin A nephropathy manifesting with nephrotic syndrome. Liu, XW., Li, DM., Xu, GS., et al.[2019]

In a study of 60 patients with IgA nephropathy, leflunomide showed a complete remission rate of 62.1% and a total effectiveness rate of 72.4%, indicating it can significantly reduce proteinuria levels.

The efficacy of leflunomide was comparable to fosinopril, with no significant differences in treatment outcomes, and both treatments had mild side effects, suggesting leflunomide is a safe option but requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of leflunomide in the treatment of immunoglobulin A nephropathy. Lou, T., Wang, C., Chen, Z., et al.[2018]

An 11-year-old child developed IgA Nephropathy two years after being diagnosed with Crohn's disease and starting treatment with the anti-TNF-α medication Adalimumab, highlighting a rare complication of this therapy.

After discontinuing Adalimumab and treating the child with steroids and an ACE inhibitor, there was significant clinical improvement, suggesting that careful monitoring of renal function is crucial for pediatric patients on anti-TNF-α therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgA nephropathy in a child: Crohn's disease-associated or adalimumab induced? Graziano, F., Busè, M., Cassata, N., et al.[2022]

In a study of 13 patients with refractory IgA nephropathy, leflunomide combined with hormone therapy significantly reduced proteinuria and increased serum albumin levels, indicating improved kidney function.

The treatment was found to be safe, with only mild and tolerable side effects reported, and it did not significantly affect serum creatinine levels, suggesting it does not harm kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy]. Rong, L., Liu, ZR.[2018]

In a randomized trial involving 86 patients with IgA nephropathy, a 6-month course of steroid treatment significantly reduced the risk of renal function deterioration compared to supportive therapy alone, with only 9 patients in the steroid group experiencing a 50% increase in plasma creatinine versus 14 in the control group.

The steroid treatment was well-tolerated, with no significant side effects reported, indicating that it is a safe option for protecting renal function in patients with this progressive kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroids in IgA nephropathy: a randomised controlled trial. Pozzi, C., Bolasco, PG., Fogazzi, GB., et al.[2022]

A patient with IgA nephropathy and Crohn disease showed clinical improvement and remission of nephropathy after treatment with a combination of prednisolone, cyclophosphamide, warfarin, and an ACE inhibitor, indicating the effectiveness of this therapy.

The recurrence of IgA nephropathy with the onset of Crohn disease suggests a potential link between the two conditions, possibly due to an IgA immune response triggered by intestinal challenges, which was successfully managed with an elemental diet and oral prednisolone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An adolescent with IgA nephropathy and Crohn disease: pathogenetic implications. Takemura, T., Okada, M., Yagi, K., et al.[2013]

Citations

1. otsuka.co.jp otsuka.co.jp/en/company/newsreleases/2025/20251110_1.html

Sibeprenlimab Phase 3 Data Presented at American Society ... Sibeprenlimab Phase 3 Data Presented at American Society of Nephrology Kidney Week 2025 Showed Proteinuria Reduction through 12 Months for the ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2512133?af=R

Sibeprenlimab in IgA Nephropathy — Interim Analysis of a ... Patients receiving sibeprenlimab had a 45.6% (95% CI, 37.2 to 52.9) lower spot urinary protein-to-creatinine ratio at month 9 than at baseline, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925006059

Evaluating Sibeprenlimab in IgA Nephropathy In IgA nephropathy trials, proteinuria reductions and eGFR decline are widely accepted surrogate end points for efficacy outcomes.,, These data ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04287985

NCT04287985 | Safety and Efficacy Study of VIS649 for IgA ... This is a Phase 2, double-blind, randomized, placebo-controlled study in patients aged 18 years and above with biopsy confirmed diagnosis of IgAN.

5. otsuka-us.com otsuka-us.com/news/otsuka-sibeprenlimab-phase-3-data-show-statistically-significant-and-clinically-meaningful

Otsuka Sibeprenlimab Phase 3 Data Show a Statistically ... In the Phase 3 VISIONARY study, sibeprenlimab achieved a statistically significant and clinically meaningful 51.2% (P<0.0001) reduction in ...