LNP023 for Complement 3 Glomerulopathy

Recruiting at 59 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Advanced cardiac disease, Severe infections, ECG abnormalities, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 66 months

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term effects of iptacopan (LNP023) on individuals with specific kidney conditions, including C3 glomerulopathy (C3G) and idiopathic immune-complex-membranoproliferative glomerulonephritis (IC-MPGN). Researchers aim to assess the safety and effectiveness of this treatment over time. It is intended for those who have participated in earlier related studies and are continuing with the treatment. Participants should have completed the treatment phase of one of these previous studies and should not have severe heart or lung issues or recent serious infections. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that iptacopan, also known as LNP023, is generally safe for individuals with conditions like C3 glomerulopathy (C3G) and idiopathic immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). Studies indicate that serious side effects are rare.

For C3G patients, one study found that iptacopan significantly improved kidney function over time without major safety concerns. Another study revealed no new safety issues after more than nine months of use.

Similarly, for those with IC-MPGN, research has demonstrated that iptacopan is safe for long-term use, with no major side effects reported.

These studies suggest that iptacopan is generally safe for the conditions mentioned, making it a promising option for individuals considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for C3 glomerulopathy?

Iptacopan is unique because it targets the complement pathway, specifically inhibiting factor B, which plays a key role in the development of Complement 3 Glomerulopathy (C3G). Unlike conventional treatments like steroids and immunosuppressants that broadly suppress the immune system, iptacopan precisely targets the underlying mechanism of C3G. This precision may lead to fewer side effects and improved disease management. Researchers are excited about iptacopan because of its potential to provide a more effective and safer treatment option for patients with C3G and related conditions.

What evidence suggests that LNP023 might be an effective treatment for C3 glomerulopathy?

Research shows that iptacopan may help treat C3 glomerulopathy (C3G). In this trial, participants in various cohorts will receive iptacopan to assess its effectiveness. A previous study found that patients taking iptacopan had significantly less protein in their urine, indicating improved kidney health, and were seven times more likely to reach a key kidney health goal compared to those on a placebo. For idiopathic immune-complex-membranoproliferative glomerulonephritis (IC-MPGN), this trial examines iptacopan's potential to manage the condition by affecting a part of the immune system. Early research suggests that iptacopan might offer long-term kidney health benefits for both conditions. ^{5 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 patients who have completed the CLNP023X2202 trial for C3 glomerulopathy. It's not open to those with HIV, severe diseases like advanced heart disease or pulmonary hypertension, active infections close to screening time, fever shortly before screening, or certain ECG abnormalities.

Inclusion Criteria

- Patients must have completed the treatment period of the CLNP023X2202 trial on study drug

Exclusion Criteria

I haven't had a serious infection or fever over 100.4°F in the last 14 days.

History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects

Severe concurrent co-morbidities, e.g. advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating LNP023 or complying with the requirements of the study

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 efficacy, safety, and tolerability

Up to 66 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Continued access to iptacopan for participants from Phase 3 programs until the drug becomes commercially available

Up to 66 months

What Are the Treatments Tested in This Trial?

Interventions

• LNP023

Trial Overview The study tests the long-term effects of a drug called LNP023 on people with C3 glomerulopathy. As an open-label extension study, all participants know they are receiving LNP023 and its impact over a longer period will be observed.

How Is the Trial Designed?

Group I: Cohort F: participants with IC-MPGN randomized to ipatocan in CLNP023B12302 Experimental Treatment 1 Intervention

IC-MPGN participants (adults and adolescents) from study CLNP023B12302 who were randomized to iptacopan in the core study receiving iptacopan capsules 200mg b.i.d

Group II: Cohort E: participants with IC-MPGN randomized to placebo in CLNP023B12302 Experimental Treatment 1 Intervention

IC-MPGN participants (adults and adolescents) from study CLNP023B12302 who were randomized to placebo in the core study receiving iptacopan capsules 200mg b.i.d

Group III: Cohort D: particpants with native C3G randomised to iptacopan in CLNP023B12301 Experimental Treatment 1 Intervention

Native C3G participants (adults and adolescents) from study CLNP023B12301 who were randomized to iptacopan in the core study. Receiving iptacopan capsules 200mg b.i.d

Group IV: Cohort C: Participants with native C3G randomized to placebo in CLNP023B12301 Experimental Treatment 1 Intervention

Native C3G Participants (adults and adolescents) from CLNP023B12301 study who were randomized to placebo in the core study receiving iptacopan capsules 200mg b.i.d

Group V: Cohort B: participants with transplanted kidneys and recurrent C3G from CLNP023X2202 Experimental Treatment 1 Intervention

C3G participants from study CLNP023X2202 who have undergone kidney transplant and have recurrence of C3G receiving iptacopan capsules 200 mg b.i.d

Group VI: Cohort A: participants with native kidneys from CLNP023X2202 Experimental Treatment 1 Intervention

C3G participants from study CLNP023X2202 with native kidneys receiving iptacopan capsules 200 mg b.i.d

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

In a study of 29 patients with C3 glomerulopathy (C3G), significant systemic activation of the alternative complement pathway was observed, indicated by reduced levels of C3 and C5 and elevated levels of sC5b-9, which are important biomarkers for understanding the disease's progression.

Strong correlations were found between complement biomarkers and kidney function, with lower eGFR associated with higher baseline concentrations of Ba and factor D, suggesting that these biomarkers could help characterize the severity and progression of C3G.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Clinical Characteristics and Complement Biomarkers of Patients with C3 Glomerulopathy Enrolled in Two Phase 2 Studies Investigating the Factor D Inhibitor Danicopan. Podos, SD., Trachtman, H., Appel, GB., et al.[2023]

Iptacopan, a selective inhibitor of factor B in the alternative complement pathway, is being evaluated in a Phase III study involving 68 adults with complement 3 glomerulopathy (C3G) to assess its efficacy and safety in reducing proteinuria and improving kidney function.

The study aims to show that iptacopan can significantly reduce protein levels in urine (measured by urine protein:creatinine ratio) compared to a placebo, potentially offering a new treatment option for patients with this rare kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. Bomback, AS., Kavanagh, D., Vivarelli, M., et al.[2022]

In a study of 21 patients with post-transplant complement 3 glomerulopathy (C3G), early recurrence of the disease was observed in six patients within the first month, indicating a significant risk of graft dysfunction shortly after transplantation.

The long-term clinical outcomes were poor, with only 28% of patients maintaining stable graft function after 140 months, while 34% experienced graft loss and 19% died, highlighting the challenges in managing C3G post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor allograft outcome in Indian patients with post-transplant C3 glomerulopathy. Kumar, A., Ramachandran, R., Rawat, A., et al.[2022]

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]

Danicopan, an orally active factor D inhibitor, was tested in two phase 2 studies for its efficacy in treating C3 glomerulopathy (C3G) and showed a favorable safety profile, but did not achieve the necessary levels of complement inhibition for effective treatment.

Despite some patients showing stable disease or improvement, the overall clinical response was limited due to inadequate and inconsistent inhibition of the alternative pathway of complement, highlighting the need for complete and sustained inhibition for effective treatment in C3G.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies. Nester, C., Appel, GB., Bomback, AS., et al.[2023]

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]

Avacopan, a C5aR antagonist, was safely administered to a child with C3 glomerulonephritis (C3GN) in a Phase 2 clinical trial, demonstrating good tolerability and safety.

The patient was able to discontinue the use of mycophenolate mofetil (MMF) while maintaining remission from C3GN, suggesting that avacopan may be an effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment with avacopan (CCX168) in a pediatric patient with C3 glomerulonephritis. Zotta, F., Diomedi-Camassei, F., Gargiulo, A., et al.[2023]

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 (LNP023) is a promising oral treatment for atypical hemolytic uremic syndrome (aHUS), showing potential for effective complement inhibition and convenience compared to current intravenous therapies.

The ongoing Phase 3 study (APPELHUS) will evaluate the safety and efficacy of iptacopan in 50 patients with aHUS, focusing on achieving a complete response to thrombotic microangiopathy without the need for plasma exchange or anti-C5 therapy over 26 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Rationale of the APPELHUS Phase 3 Open-Label Study of Factor B Inhibitor Iptacopan for Atypical Hemolytic Uremic Syndrome. Kavanagh, D., Greenbaum, LA., Bagga, A., 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924023222

12-MONTH RESULTS FROM THE PHASE 3 APPEAR-C3G ... Iptacopan demonstrated a significant and clinically meaningful proteinuria reduction on top of supportive care at 6 months in the APPEAR-C3G study; sustained up ...

2. fabhalta-hcp.com fabhalta-hcp.com/c3g/efficacy

C3G Efficacy | FABHALTA® (iptacopan) HCP FABHALTA-treated patients had 7-fold higher odds (P=.0166) of achieving a composite renal end point vs placebo-treated patients at Month 6.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04817618

NCT04817618 | Study of Efficacy and Safety of Iptacopan ... CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in ...

4. novartis.com novartis.com/news/media-releases/novartis-oral-fabhalta-iptacopan-sustained-clinically-meaningful-results-one-year-phase-iii-c3-glomerulopathy-c3g-trial

Novartis oral Fabhalta® (iptacopan) sustained clinically ... New APPEAR-C3G data show Fabhalta sustained proteinuria reduction at 12 months1; Upon Fabhalta initiation, improvement observed in estimated ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41016405/

Oral iptacopan therapy in patients with C3 glomerulopathy We aimed to assess efficacy and safety of iptacopan (LNP023) ... Serious adverse events were reported in three (8%) participants in the iptacopan ...

6. 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 ... A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in ...

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

Efficacy and Safety of Iptacopan in Patients With C3 ... Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03955445

Study Details | NCT03955445 | Long-term Efficacy, Safety ... The primary (at 9 months) and longer-term (>9 months) efficacy and safety data of iptacopan collected from CLNP023X2202 participants will be used to support ...

9. kireports.org kireports.org/article/S2468-0249(24)03121-8/fulltext

WCN25-1242 UPDATE TO THE LONG-TERM SAFETY ... Here we present further long-term efficacy and safety data from patients with native C3G and recurrent C3G (post-kidney transplantation), who completed 33M of ...