Sibeprenlimab for IgA Nephropathy

Not currently recruiting at 339 trial locations

Overseen By Otsuka Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Must be taking: ACEI, ARB, SGLT2i

Must not be taking: Immunosuppressants, Glucocorticoids

Disqualifiers: Chronic kidney disease, Diabetes, 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: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effects of a new treatment called sibeprenlimab for IgA nephropathy, a kidney disease that can lead to protein in the urine and issues with kidney function. The researchers seek to determine how well sibeprenlimab improves these kidney-related problems when administered every four weeks. Participants will be divided into two groups: one receiving the treatment and the other a placebo. Individuals diagnosed with IgA nephropathy and already on standard treatments like ACE inhibitors might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable dose of ACEI, ARB, or SGLT2i for at least 3 months before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sibeprenlimab, a treatment for IgA nephropathy (a kidney disease), has undergone safety testing in humans. In a previous study, patients taking sibeprenlimab had less protein in their urine, a positive indicator. Importantly, the study found no major safety issues, suggesting the treatment was generally well-tolerated.

Another study on sibeprenlimab's safety found it to be a promising treatment option with no serious side effects reported. Most participants did not experience severe negative effects, indicating good safety.

Since sibeprenlimab is in a phase 3 study, it has already passed earlier safety tests, demonstrating it is safe enough for larger groups. However, discussing any concerns with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

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

Most treatments for IgA Nephropathy focus on controlling symptoms and slowing disease progression through blood pressure medications or immunosuppressants. But Sibeprenlimab works differently, targeting the immune system in a novel way. This treatment is designed to block a specific protein involved in the disease's progression, potentially offering more precise management of IgA Nephropathy. Researchers are excited because it could provide a more targeted approach with fewer side effects compared to traditional therapies. This new mechanism of action offers hope for better outcomes for patients with this challenging kidney condition.

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

Research shows that sibeprenlimab, which participants in this trial may receive, effectively treats IgA nephropathy, a type of kidney disease. Studies have found that this treatment can significantly reduce protein in urine, a key sign of kidney damage. In one study, sibeprenlimab reduced protein in urine by 51.2%, a result both statistically significant and important for health. This reduction indicates that sibeprenlimab helps protect kidney function. Additional research shows that patients who received sibeprenlimab experienced a slower decline in kidney health compared to those who did not receive the treatment. Overall, these findings support the effectiveness of sibeprenlimab in managing IgA nephropathy. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

Adults with IgA Nephropathy (IgAN) who've been on a stable dose of certain kidney medications for at least 3 months can join. They need to have a specific level of protein in their urine and their kidneys must be functioning above a certain threshold. People with other kidney diseases, uncontrolled diabetes or hypertension, or those on recent immunosuppressants can't participate.

Inclusion Criteria

I have been on a stable dose of heart medication for at least 3 months.

I have IgA nephropathy confirmed by a biopsy.

The amount of protein in your urine is too high.

Exclusion Criteria

I have not taken part in another drug trial within the last 30 days or 5 half-lives of the drug.

I have not taken immunosuppressants, including steroids, in the last 16 weeks.

I have been diagnosed with nephrotic syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sibeprenlimab 400 mg subcutaneously every 4 weeks or placebo for 9 months

9 months

Extended Treatment

Participants continue treatment to evaluate the annualized rate of change in eGFR over approximately 24 months

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sibeprenlimab

Trial Overview The trial is testing Sibeprenlimab, given as an injection every four weeks, against a placebo. Participants also continue their usual care for IgAN. The study aims to see if Sibeprenlimab helps reduce protein in the urine and affects kidney function over time.

How Is the Trial Designed?

Group I: Sibeprenlimab 400 mg s.c. q 4weeks Active Control 1 Intervention

Group II: Placebo Placebo Group 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 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 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]

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]

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]

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 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]

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]

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]

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).