Iptacopan for Membranoproliferative Glomerulonephritis

(APPARENT Trial)

Recruiting at 72 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

Trial Summary

What is the purpose of this trial?

This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.

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.

How is the drug Iptacopan different from other treatments for membranoproliferative glomerulonephritis?

Iptacopan is unique because it targets the complement system, which is involved in the abnormal immune response seen in membranoproliferative glomerulonephritis. This approach is different from traditional treatments like steroids or immunosuppressants, which have varied effectiveness and can have significant side effects. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Idiopathic membranoproliferative glomerulonephritis in Japanese children. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

Cyclosporine in the treatment of membranoproliferative glomerulonephritis. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Membranoproliferative glomerulonephritis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Fundus changes in type III membranoproliferative glomerulonephritis: a case report. [2018]