Iptacopan for IgA Nephropathy

Recruiting at 166 trial locations

Overseen By Peter Santos

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: ACEi, ARB

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Severe urinary obstruction, AKI, RPGN, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 6

Duration: Up to 3 years

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called iptacopan to determine its safety and effectiveness for people with IgA nephropathy, a kidney disease that can cause kidney damage. The trial aims to gather long-term safety information and assess the drug's effectiveness over time. Individuals who have participated in and completed similar trials successfully might be suitable candidates. Participants should have up-to-date vaccinations and follow a supportive care regimen for kidney health. As a Phase 3 trial, this is the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

Participants must continue taking ACE inhibitors or ARBs as part of their supportive care. However, if you are on immunosuppressive drugs or certain other medications, you may need to stop them before starting the trial, with specific washout periods required for some drugs.

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

Previous studies have shown that iptacopan is well-tolerated by patients. Research indicates it can significantly reduce excess protein in urine for those with IgA nephropathy, a condition where the immune system harms the kidneys.

Reports from other trials show that iptacopan was generally safe for patients. Participants experienced few side effects, and any that occurred were manageable. These studies demonstrated strong results over six months, suggesting that iptacopan could be a promising treatment option with minimal 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 often include corticosteroids and immunosuppressive drugs, iptacopan (also known as LNP023) offers a novel approach by specifically targeting the alternative complement pathway. This pathway is a part of the immune system that, when overactivated, can lead to kidney damage in IgA nephropathy patients. By inhibiting this specific pathway, iptacopan aims to reduce kidney inflammation and damage more directly and potentially with fewer side effects than broad immunosuppression. Researchers are excited about iptacopan because it represents a targeted therapy that could offer improved efficacy and safety for patients with this condition.

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

Research has shown that iptacopan holds promise for treating IgA nephropathy, a kidney disease. Studies have found that iptacopan slows the worsening of kidney function in these patients. It effectively reduces proteinuria, meaning there is less protein in the urine. This reduction is important because it usually indicates improved kidney function. Iptacopan is also well-tolerated, with patients generally not experiencing serious side effects. Overall, evidence suggests iptacopan could effectively manage IgA nephropathy. ^{1 2 3 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people with a kidney condition called primary IgA nephropathy who finished earlier trials (CLNP023X2203 or CLNP023A2301). They should be up-to-date on certain vaccinations and judged by their doctor to benefit from the drug iptacopan. Participants must also follow specific guidelines for kidney care and have a minimum eGFR of 20 ml/min/1.73m2.

Inclusion Criteria

I am taking ACE inhibitors or ARBs as part of my treatment plan.

For LNP023X2203, participants must have completed part 1 or part 2 of the trial

I can't take certain blood pressure medicines due to allergies or intolerance.

Exclusion Criteria

I have severe problems urinating or other urinary tract issues not related to IgAN.

I haven't taken strong immune system affecting drugs recently.

I am not using any experimental drugs or haven't used any in the last 30 days or 5 half-lives, whichever is longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label iptacopan to evaluate long-term safety and tolerability

Up to 3 years

Visits every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days after last administration

Open-label extension

Participants may continue treatment with iptacopan until marketing authorizations are received or other specified conditions are met

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Iptacopan/LNP023

Trial Overview The study tests the long-term safety and effects of iptacopan, an investigational drug, in patients with IgA nephropathy. It's open-label, meaning everyone knows they're getting iptacopan, and it continues until the drug is commercially available.

How Is the Trial Designed?

Group I: LNP023 Experimental Treatment 1 Intervention

All participants are receiving 200 mg b.i.d

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

Approved in United States as Fabhalta for:

• Paroxysmal Nocturnal Hemoglobinuria
• Primary Immunoglobulin A Nephropathy

Approved in European Union as Fabhalta for:

• Paroxysmal Nocturnal Hemoglobinuria
• Primary Immunoglobulin A Nephropathy

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

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, 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]

Iptacopan, a first-in-class oral complement inhibitor, showed a 71% absorption rate in healthy volunteers, with a peak concentration reached in 1.5 hours and a half-life of 12.3 hours, indicating effective systemic availability for therapeutic use.

The drug is primarily eliminated through hepatic metabolism, with the main pathways involving CYP2C8 and UGT1A1, suggesting a low risk associated with its metabolites based on toxicology studies in rats and dogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, Distribution, Metabolism, and Excretion of [14C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies. James, AD., Kulmatycki, K., Poller, B., et al.[2023]

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]

Corticosteroids and fish oil capsules have shown the most promise as treatment options for patients with IgA nephropathy, based on recent publications.

A multicenter, placebo-controlled study is underway to evaluate the effectiveness of alternate-day prednisone and highly purified fish oil concentrate in children and young adults with moderately severe IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in treatment: immunoglobulin A nephropathy. Hogg, RJ., Waldo, B.[2007]

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

Results of a randomized double-blind placebo-controlled ... Iptacopan was well-tolerated, with no reports of deaths, treatment-related serious adverse events or bacterial infections, and led to strong ...

3. 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 ...

4. medcommshydhosting.com medcommshydhosting.com/CRM/Renal//ASN/presentations/2024/posters/ASN2024_Safety_and_efficacy_of_iptacopan_Poster.pdf

Safety and Efficacy of Iptacopan in Patients with IgA ... • IgA nephropathy (IgAN) is the most common primary glomerulonephritis ... • Pharmacokinetic (PK) concentration-time data from 6 patients in the iptacopan arm ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39453772/

Alternative Complement Pathway Inhibition with Iptacopan ... Among patients with IgA nephropathy, treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria as compared with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468024922005770

POS-546 EFFICACY AND SAFETY OF IPTACOPAN IN IgA ... Iptacopan was well tolerated and led to continuous reduction in proteinuria and strong inhibition of AP activity through 6 months in patients with IgAN.