Iptacopan for IgA Nephropathy

Recruiting at 136 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?

The purpose of this study is to evaluate the long-term safety and tolerability, of open label iptacopan in primary IgA nephropathy participants who have completed either the CLNP023X2203 or CLNP023A2301 clinical trials. The open-label design of the current study is appropriate to provide study participants the opportunity to receive treatment with iptacopan until marketing authorizations are received and the drug product becomes commercially available while enabling collection of long-term safety and tolerability data for the investigational drug. Furthermore efficacy assessments conducted every 6 months will afford the opportunity to evaluate the clinical effects of iptacopan on long-term disease progression.

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 iptacopan safe for human use?

Iptacopan has been well-tolerated in studies for IgA nephropathy and paroxysmal nocturnal hemoglobinuria, with no reports of deaths, serious adverse events, or severe side effects. It was also well-tolerated in healthy volunteers, with its metabolism and elimination pathways well understood, suggesting a low risk associated with its use. ^{1 2 3 4 5}

How is the drug Iptacopan different from other treatments for IgA nephropathy?

Iptacopan is unique because it is an oral drug that specifically targets and inhibits the alternative complement pathway, which plays a role in the development of IgA nephropathy. This mechanism of action is different from traditional treatments like corticosteroids or tonsillectomy, which do not specifically target this pathway. ^{1 2 3 5 6}

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

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]

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]

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]

Citations

1. United States 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. [2023]

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

Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. [2022]

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

Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study. [2023]

4. United States 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. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

Comparison of oral steroids with tonsillectomy plus steroid pulse therapy in patients with IgA nephropathy. [2018]

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

Advances in treatment: immunoglobulin A nephropathy. [2007]