Sibeprenlimab for IgA Nephropathy

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

530 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests injections of sibeprenlimab in adults with IgA Nephropathy who are on standard treatment. The drug aims to reduce harmful proteins in urine and help maintain kidney function.

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.

What data supports the effectiveness of the drug Sibeprenlimab for IgA Nephropathy?

Research shows that Sibeprenlimab, a drug that blocks a protein called APRIL, can significantly reduce levels of certain antibodies (proteins made by the immune system) in the blood, which are involved in IgA Nephropathy. In studies with healthy participants, it was found to be safe and effectively lowered these antibodies in a dose-dependent manner, suggesting potential benefits for patients with IgA Nephropathy. ^{1 2 3 4 5}

Is Sibeprenlimab safe for humans?

In studies with healthy participants, Sibeprenlimab was generally safe, with no serious side effects reported. Some participants experienced mild adverse events, but none were severe enough to stop the study. ^{1 2 3 6 7}

How is the drug Sibeprenlimab different from other treatments for IgA Nephropathy?

The research provided does not contain specific information about Sibeprenlimab, so I cannot determine how it differs from other treatments for IgA Nephropathy. ^{4 8 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

References

1. 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]

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

Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Sibeprenlimab in Healthy Participants. [2023]

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

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

4. Germany 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. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

An adolescent with IgA nephropathy and Crohn disease: pathogenetic implications. [2013]

6. Netherlands 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. [2023]

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

Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy]. [2018]

9. Australia pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of leflunomide in the treatment of immunoglobulin A nephropathy. [2018]

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

IgA nephropathy in a child: Crohn's disease-associated or adalimumab induced? [2022]

11. England pubmed.ncbi.nlm.nih.gov

Corticosteroids in IgA nephropathy: a randomised controlled trial. [2022]