LNP023 for IgA Nephropathy

(APPLAUSE-IgAN Trial)

No longer recruiting at 251 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: ACEi, ARB

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Secondary IgAN, Hypertension, Infections, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

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 tests a new treatment called iptacopan (LNP023) to determine its effectiveness in helping people with IgA nephropathy, a kidney disease that can lead to kidney damage. The goal is to see if this treatment can reduce protein in the urine and slow the progression of kidney function decline, compared to a placebo. Individuals diagnosed with IgA nephropathy who experience persistent protein in their urine might be suitable candidates, especially if they are already on certain medications for their condition. 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 requires that you stay on a stable dose of ACE inhibitors or ARBs for about 90 days before starting the study drug. If you're taking other medications for IgA nephropathy, those doses should also be stable for about 90 days before the trial begins.

Is there any evidence suggesting that LNP023 is likely to be safe for humans?

Research has shown that iptacopan (LNP023) is generally well-tolerated by patients. In a previous study, 23 people took 200 mg of iptacopan twice a day for at least a year. Safety information from this group indicated the treatment is quite safe, with no major safety issues reported.

While minor side effects can occur with any treatment, evidence so far supports iptacopan's safety. It's important to remember that this treatment is still under study, but the current data is reassuring. ^{1 2 3 4 5}

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

Researchers are excited about LNP023 for IgA Nephropathy because it offers a fresh approach to treatment by targeting the alternative complement pathway, which is thought to play a crucial role in the disease. Unlike current treatments, which often involve steroids and immunosuppressants, LNP023 is designed to more directly modulate immune activity with potentially fewer side effects. This new mechanism of action could mean more effective management of the condition, offering hope for better outcomes for patients dealing with IgA Nephropathy.

What evidence suggests that LNP023 might be an effective treatment for IgA Nephropathy?

This trial will evaluate the effectiveness of iptacopan (LNP023) for treating IgA nephropathy, a kidney condition. Research has shown that iptacopan is promising, as it significantly slowed the decline in kidney function in patients with this condition. Previous studies suggest that iptacopan works by blocking a part of the immune system that can damage the kidneys. Patients taking iptacopan showed lower levels of protein in their urine, a positive sign for kidney health. Overall, these findings suggest that iptacopan could effectively help manage IgA nephropathy. Participants in this trial will receive either LNP023 or a placebo. ^{2 5 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with biopsy-confirmed IgA nephropathy, a kidney disease, and certain levels of protein in their urine can join. They must have been on stable doses of specific blood pressure medicines for about 90 days. Vaccinations against certain infections are required before starting the trial.

Inclusion Criteria

I am 18 or older with IgA nephropathy confirmed by biopsy and kidney function test.

My kidney function is low, but a biopsy showed less than 50% damage.

I have IgA nephropathy with high protein levels in my urine.

Exclusion Criteria

I have IgA nephropathy linked to another health condition.

You have a history of frequent serious infections caused by certain types of bacteria like meningococcus and pneumococcus.

I have not had any serious infections like COVID-19 in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iptacopan (LNP023) or placebo to evaluate efficacy and safety in reducing proteinuria and slowing renal disease progression

9 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on long-term efficacy based on eGFR decline

15 months

What Are the Treatments Tested in This Trial?

Interventions

• LNP023

Trial Overview The trial is testing if LNP023 (iptacopan) is better than a placebo at reducing proteinuria and slowing down kidney disease when taken alongside standard treatments. Participants will be randomly assigned to either the drug or placebo group without knowing which one they're getting.

How Is the Trial Designed?

Group I: LNP023 200mg b.i.d Experimental Treatment 1 Intervention

Group II: Placebo to LNP023 200mg b.i.d Placebo Group 1 Intervention

LNP023 is already approved in United States, European Union for the following indications:

Approved in United States as FABHALTA for:

• Paroxysmal nocturnal hemoglobinuria (PNH)

Approved in European Union as FABHALTA for:

• Paroxysmal nocturnal hemoglobinuria (PNH)

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

Published Research Related to This Trial

Atacicept, a B-cell-targeted immunomodulator, demonstrated an acceptable safety profile in a phase II study involving 16 patients with IgA nephropathy, with most treatment-emergent adverse events being mild or moderate.

The treatment led to significant reductions in pathogenic Gd-IgA1 levels and early improvements in proteinuria, while renal function remained stable compared to a decline observed in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria. Barratt, J., Tumlin, J., Suzuki, Y., et al.[2022]

In a study of 66 IgA nephropathy patients, those treated with tonsillectomy plus steroid pulse (TSP) therapy showed significantly higher clinical remission rates compared to those treated with oral prednisolone (oPSL) at 12, 36, and 72 months.

TSP therapy not only resulted in better preservation of renal function but also had fewer adverse events (11.5% vs. 34.6%) compared to oPSL, indicating it may be a safer and more effective treatment option for IgAN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of oral steroids with tonsillectomy plus steroid pulse therapy in patients with IgA nephropathy. Hoshino, Y., Moriyama, T., Uchida, K., et al.[2018]

Iptacopan, an oral complement inhibitor, showed a significant dose-response effect in reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN), with a 23% reduction in urine protein-to-creatinine ratio at the highest dose after three months.

The treatment was well-tolerated with no serious adverse events reported, indicating a favorable safety profile, and it demonstrated sustained reductions in complement biomarkers, supporting its potential for further evaluation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Zhang, H., Rizk, DV., Perkovic, V., et al.[2023]

LNP023 significantly improved lupus nephritis (LN) in MRL/lpr mice by reducing lupus-like symptoms, enhancing renal function, and decreasing harmful immune complex deposition in the kidneys after 2 weeks of treatment.

The mechanism of action for LNP023 involves inhibiting complement factor B (CFB) in the alternative complement pathway, which leads to reduced expression of key complement proteins and regulation of important targets like AKT and TNF-α.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice. Chen, K., Deng, Y., Shang, S., et al.[2022]

In a phase 2 study involving 13 patients with paroxysmal nocturnal hemoglobinuria (PNH), iptacopan demonstrated significant efficacy, with 12 out of 12 evaluable patients achieving a reduction in serum lactate dehydrogenase (LDH) levels by at least 60% by week 12, indicating effective control of hemolysis.

Iptacopan was well tolerated with no severe adverse events reported, and most patients experienced clinically meaningful improvements in hemoglobin levels, remaining transfusion-free for up to 12 weeks, showcasing its potential as a safe and effective monotherapy for treatment-naïve PNH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Jang, JH., Wong, L., Ko, BS., et al.[2022]

Iptacopan, a complement inhibitor, is being evaluated in a Phase 3 study (APPLAUSE-IgAN) involving approximately 450 adults with immunoglobulin A nephropathy (IgAN) to determine its efficacy in reducing proteinuria and slowing kidney function decline over 24 months.

The primary goal of the study is to show that iptacopan is superior to placebo in reducing the urine protein-to-creatinine ratio and in slowing the decline of estimated glomerular filtration rate, with safety and tolerability also being assessed as secondary outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study. Rizk, DV., Rovin, BH., Zhang, H., et al.[2023]

Citations

1. novartis.com novartis.com/news/media-releases/novartis-fabhalta-iptacopan-meets-phase-iii-primary-endpoint-slows-kidney-function-decline-patients-iga-nephropathy-igan

Novartis Fabhalta® (iptacopan) meets Phase III primary ... Novartis Fabhalta® (iptacopan) meets Phase III primary endpoint, slows kidney function decline in patients with IgA nephropathy (IgAN) · Novartis.

2. kidney-international.org kidney-international.org/article/S0085-2538(23)00754-8/fulltext

Results of a randomized double-blind placebo-controlled ... Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy.

3. nejm.org nejm.org/doi/pdf/10.1056/NEJMoa2410316

Alternative Complement Pathway Inhibition with Iptacopan ... Given these results, we expect that iptacopan has a high likelihood of showing benefits for kidney function. This trial is one of several that ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10166738/

Design and Rationale of the APPLAUSE-IgAN Study APPLAUSE-IgAN will evaluate the benefits and safety of iptacopan, a novel targeted therapy for IgAN, in reducing complement-mediated kidney damage.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04578834

NCT04578834 | Study of Efficacy and Safety of LNP023 in ... The purpose of the study is to evaluate the efficacy and safety of iptacopan (LNP023) compared to placebo on proteinuria reduction and slowing disease ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03373461

NCT03373461 | Study of Safety and Efficacy of LNP023 in ... This was a multicenter, randomized, double-blind, dose-ranging, parallel-group study with an adaptive design (Part 1 informed the design adaptations for ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/218276Orig1s000IntegratedR.pdf

218276Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov ... iptacopan 200 mg. BID, 23 of whom received iptacopan for at least 12 months, providing supportive safety data. This safety database is reasonable and ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37914086/

Results of a randomized double-blind placebo-controlled ... Iptacopan (LNP023) is an oral, proximal alternative complement inhibitor that specifically binds to Factor B.