Iptacopan for Membranoproliferative Glomerulonephritis

(APPARENT Trial)

Recruiting at 127 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: RAS inhibitors

Must not be taking: Complement inhibitors, Immunosuppressants

Disqualifiers: Transplantation, Chronic infections, Autoimmune diseases, 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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

106 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, iptacopan, to determine its effectiveness for idiopathic immune complex mediated membranoproliferative glomerulonephritis, a kidney condition that impairs waste filtration and leads to health issues. Participants will receive either iptacopan or a placebo to compare effectiveness and safety. Suitable candidates must have a confirmed diagnosis of this kidney condition and have maintained stable medication doses for at least 90 days. As a Phase 3 trial, this study is the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants have been on a stable dose of certain medications, like renin angiotensin system inhibitors, for at least 90 days before joining. Some medications, like certain immunosuppressants and high-dose corticosteroids, must be stopped at least 90 days before starting the trial.

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

Research has shown that iptacopan is generally safe. In earlier studies, patients taking iptacopan did not experience any new safety issues, indicating it is well-tolerated. Reports have consistently found no unexpected side effects. Overall, the evidence so far supports that iptacopan is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for membranoproliferative glomerulonephritis?

Iptacopan is unique because it represents a new approach to treating membranoproliferative glomerulonephritis (MPGN), a rare kidney disorder. Unlike current treatments, which primarily focus on controlling symptoms with immunosuppressants or steroids, iptacopan targets the complement system, a part of the immune system involved in inflammation and disease progression. This targeted mechanism could offer a more precise and effective treatment option, reducing the need for broad immunosuppression and potentially leading to better outcomes for patients. Researchers are excited about iptacopan because it has the potential to address the root cause of MPGN, offering hope for improved management of this challenging condition.

What evidence suggests that iptacopan might be an effective treatment for membranoproliferative glomerulonephritis?

Research has shown that iptacopan, which participants in this trial may receive, may help treat membranoproliferative glomerulonephritis (MPGN), a rare kidney disease. One study successfully treated a patient with MPGN using iptacopan, highlighting its potential benefits. Real-world evidence also supports its effectiveness and safety for people with primary MPGN. Iptacopan targets certain proteins in the immune system that can harm the kidneys in this disease. This action likely reduces kidney inflammation and protein buildup. Overall, early data suggests iptacopan could be an effective treatment for MPGN. ^{2 6 7 8 9}

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 aged 12-60 with a specific kidney disease called IC-MPGN, confirmed by biopsy. Participants must have been on certain medications like ACEI or ARB for at least 90 days and have stable doses of other drugs to control protein in urine. They need a minimum kidney function level and vaccinations against specific infections before starting the study.

Inclusion Criteria

I have been on the highest dose possible of ACEI or ARB for at least 90 days.

I have been vaccinated against Haemophilus influenzae or will start antibiotics if I must begin treatment sooner.

I have a confirmed diagnosis of IC-MPGN from a recent kidney biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iptacopan or placebo for up to 18 months to evaluate efficacy and safety in reducing proteinuria and improving eGFR

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of iptacopan treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• Iptacopan

Trial Overview The study tests iptacopan's effectiveness and safety compared to a placebo in treating IC-MPGN. It's conducted across multiple centers where participants are randomly assigned to either receive iptacopan or a placebo without knowing which one they're getting.

How Is the Trial Designed?

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

iptacopan 200mg b.i.d

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

Placebo to iptacopan 200mg b.i.d.

Iptacopan is already approved in United States for the following indications:

Approved in United States as Fabhalta for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Primary immunoglobulin A nephropathy (IgAN)

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 study analyzing 156 kidney biopsies from 123 patients with C3 glomerulopathy and 33 with Ig-associated membranoproliferative GN, key histological features like cellular crescents and interstitial fibrosis were found to significantly predict worsening kidney function.

The research highlighted that factors such as estimated glomerular filtration rate (eGFR) and proteinuria at the time of biopsy are critical in assessing the risk of progression to kidney failure, emphasizing the importance of these parameters in patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis. Lomax-Browne, HJ., Medjeral-Thomas, NR., Barbour, SJ., et al.[2023]

In a study of 41 Japanese children with idiopathic membranoproliferative glomerulonephritis (MPGN) followed for nearly 9 years, most patients (71%) were identified through school urinary screenings, highlighting the importance of early detection.

Treatment with high-dose alternate-day prednisolone led to the highest remission rates of urinary abnormalities, with only one patient progressing to end-stage renal failure, suggesting that aggressive treatment can be effective with relatively few side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idiopathic membranoproliferative glomerulonephritis in Japanese children. Iitaka, K., Ishidate, T., Hojo, M., et al.[2019]

In a study of 18 patients with resistant idiopathic membranoproliferative glomerulonephritis, treatment with cyclosporine combined with low-dose prednisone led to a 94% rate of partial or complete remission of proteinuria over an average follow-up of 108 weeks.

Despite a delayed response compared to other glomerulonephritis treatments, cyclosporine demonstrated significant long-term benefits in reducing proteinuria and preserving kidney function in most patients, with only one relapse observed after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclosporine in the treatment of membranoproliferative glomerulonephritis. Bagheri, N., Nemati, E., Rahbar, K., et al.[2022]

Membranoproliferative glomerulonephritis is a rare kidney disorder that primarily affects children and young adults, characterized by changes in kidney structure and function, and can lead to end-stage renal disease.

Long-term steroid treatment appears to be effective for children with nephrotic-range proteinuria, but the overall efficacy of treatments remains uncertain, highlighting the need for more targeted studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membranoproliferative glomerulonephritis. Alchi, B., Jayne, D.[2022]

A case study of a 40-year-old woman with MPGN type III revealed multiple yellow-white deposits in the retinal pigment epithelium (RPE) and choroidal neovascularization (CNV), indicating significant retinal changes associated with this type of glomerulonephritis.

Despite the presence of CNV and subretinal fluid, the patient's vision remained excellent (20/20 in the right eye and 20/16 in the left eye) after 12 months, highlighting the importance of monitoring retinal changes in MPGN type III to prevent potential vision loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fundus changes in type III membranoproliferative glomerulonephritis: a case report. Takei, M., Obana, A., Inomata, T., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT05755386

Study of Efficacy and Safety of Iptacopan in Participants ... The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard ...

2. novartis.com novartis.com/clinicaltrials/study/nct03955445

Long-term Efficacy, Safety and Tolerability of Iptacopan in ... This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of iptacopan in subjects with C3 glomerulopathy or idiopathic ...

3. academic.oup.com academic.oup.com/ndt/article/doi/10.1093/ndt/gfaf116.0316/8295057

3432 Real-world evidence for efficacy and safety of iptacopan ... #3432 Real-world evidence for efficacy and safety of iptacopan and pegcetacoplan in patients with primary membranoproliferative ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11309753/

First Successful Treatment of a Patient with a Primary ... We report the first successful treatment of a 47-year-old man suffering from a primary immune complex-MPGN with iptacopan.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924003292

WCN24-1146 SAFETY AND EFFICACY OF IPTACOPAN IN ... IC-MPGN is an ultra-rare, fast-progressing complement-mediated kidney disease characterized by immunoglobulin deposits in the kidneys, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03955445

Long-term Efficacy, Safety and Tolerability of Iptacopan in ... The primary purpose of this extension study is to collect long-term efficacy, safety and tolerability data in eligible participants receiving open-label ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05755386

NCT05755386 | Study of Efficacy and Safety of Iptacopan ... The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard ...

8. novartis.com novartis.com/news/media-releases/novartis-presents-latest-phase-iii-fabhalta-iptacopan-data-c3-glomerulopathy-c3g-showing-clinically-meaningful-and-statistically-significant-351-proteinuria-reduction-vs-placebo

Novartis presents latest Phase III Fabhalta® (iptacopan ... The study also showed Fabhalta has a favorable safety profile with no new safety signals1. ... membranoproliferative glomerulonephritis (MPGN)4.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10719607/

Efficacy and Safety of Iptacopan in Patients With C3 ... No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by ...