Sibeprenlimab for IgA Nephropathy

Overseen By Otsuka Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Disqualifiers: Incomplete prior trial, 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: Long-term

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. The goal is to determine if sibeprenlimab is safe, tolerable, and effective when administered as a subcutaneous injection over an extended period. The trial includes those who have completed certain previous studies without safety issues and might benefit from continued treatment. Participants should also have adequate kidney function, specifically an eGFR level that meets the required minimum. As a Phase 2, Phase 3 trial, it evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in kidney disease treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that sibeprenlimab, a lab-made protein designed to combat certain diseases, is being tested for safety in treating IgA nephropathy, a kidney disease. Earlier studies have shown that sibeprenlimab may reduce proteinuria, a common issue for people with IgA nephropathy characterized by excess protein in the urine.

Regarding safety, previous studies found that sibeprenlimab is generally well-tolerated by patients. Some mild to moderate side effects were reported, but major safety concerns were uncommon. Now in phase 2/3 trials, this treatment has already undergone some safety testing. This suggests a reasonable safety profile for sibeprenlimab, but ongoing trials will provide more detailed information about any potential risks. ^{1 2 3 4 5}

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

Unlike the standard treatments for IgA nephropathy, which mostly involve corticosteroids and immunosuppressants to manage symptoms, Sibeprenlimab offers a novel approach by targeting the immune system in a more precise way. Researchers are excited about Sibeprenlimab because it is designed to inhibit a specific part of the immune response, potentially reducing inflammation and kidney damage more effectively. Additionally, Sibeprenlimab is administered subcutaneously every four weeks, which could offer a more convenient dosing schedule compared to some current therapies that require more frequent administration.

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

Research shows that sibeprenlimab, which participants in this trial will receive, could help treat IgA nephropathy (IgAN), a kidney disease. Studies have found that sibeprenlimab significantly lowers protein levels in urine, a sign of kidney damage. One study reported a 51.2% decrease in these protein levels, indicating the treatment's effectiveness. This improvement was both statistically significant and important for health. Overall, these findings suggest that sibeprenlimab may help protect kidney function in people with IgAN. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for people with a kidney condition called IgA Nephropathy who have a certain level of kidney function (eGFR ≥ 20 mL/min/1.73 m2) and completed previous trials without safety issues. It's not open to those who didn't finish the earlier studies or developed conditions that would have excluded them.

Inclusion Criteria

I completed a specific trial without safety issues and might benefit from sibeprenlimab.

Your kidney function, as measured by eGFR, is at least 20 mL/min/1.73 m2.

Exclusion Criteria

Subjects who have not completed participation in trials 417-201-00007 or VIS649-201.

You developed a condition after participating in previous trials that would have kept you from joining this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 400 mg of sibeprenlimab subcutaneously every 4 weeks

Long-term

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 study tests Sibeprenlimab, given as an injection under the skin every four weeks, to see how safe and effective it is over time for treating IgA Nephropathy.

How Is the Trial Designed?

Group I: Sibeprenlimab 400 mg s.c. q 4 weeks 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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. 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 ...

2. 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 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2305635

A Phase 2 Trial of Sibeprenlimab in Patients with IgA ... In patients with IgA nephropathy, 12 months of treatment with sibeprenlimab resulted in a significantly greater decrease in proteinuria than placebo.

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

Safety and Efficacy Study of VIS649 for IgA Nephropathy 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. renalandurologynews.com renalandurologynews.com/news/phase-3-trial-sibeprenlimab-proteinuria-iga-nephropathy-treatment-risk/

Phase 3 Trial Results Show Sibeprenlimab Reduces ... Sibeprenlimab clinically reduces proteinuria in adults with immunoglobulin A nephropathy (IgAN), according to data from a prespecified analysis of the phase 3 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9091613/

Safety, Tolerability, Pharmacokinetics, and ... VIS649 (sibeprenlimab), a humanized IgG2 monoclonal antibody that inhibits APRIL, is being developed as a potential treatment for IgA nephropathy (IgAN).