What is the mechanism of action of this treatment?

Complement 3 Glomerulopathy (C3G) is primarily driven by dysregulation of the alternative complement pathway, leading to excessive deposition of complement proteins in the kidneys. Treatments like Iptacopan, a selective Factor B inhibitor, work by targeting and inhibiting Factor B, a key protein in the alternative pathway. This inhibition reduces the formation of the C3 convertase enzyme, thereby decreasing the activation and deposition of complement proteins that cause kidney damage. By controlling this pathway, these treatments aim to prevent further kidney injury and preserve renal function, which is crucial for improving outcomes in C3G patients.

What side effects are associated with this type of intervention?

Common treatments for Complement 3 Glomerulopathy (C3G) that target the complement system, such as eculizumab and other complement inhibitors, often have side effects including increased risk of infections (especially meningococcal infections), infusion-related reactions, and potential development of antibodies against the drug. Other side effects may include headache, hypertension, and gastrointestinal symptoms. It is important for patients to be closely monitored for these adverse effects during treatment.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Complement 3 Glomerulopathy (C3G). However, treatments targeting the alternative complement pathway, such as selective Factor B inhibitors like Iptacopan, are being studied. These treatments aim to inhibit components of the complement system to reduce kidney inflammation and damage. Other investigational drugs in this category include eculizumab, a C5 inhibitor, which has been used off-label for C3G. The development of these therapies represents a promising area of research for managing C3G.

What other types of research exist?

Pegcetacoplan, a pegylated peptide targeting complement C3, is a promising novel alternative to Iptacopan for C3G patients. It potentially inhibits both intravascular and extravascular hemolysis, making it a viable option for treatment in 2024.

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Complement Inhibitor

Iptacopan for Complement 3 Glomerulopathy (APPEAR-C3G Trial)

Phase 3

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents

Male and female participants age ≥ 12 and ≤ 60 years at screening

Must not have

The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti C5 antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit

Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%

Timeline

Screening 3 weeks

Treatment Varies

Follow Up month 6, month 12 (open-label)

Awards & highlights

Pivotal Trial

Summary

This trial is testing iptacopan, a medication, in patients with a rare kidney disease called C3G. The drug aims to reduce kidney damage by calming an overactive part of the immune system. Researchers are evaluating its effects to see if it can improve kidney function and reduce protein levels in urine.

Who is the study for?

This trial is for people aged 12-60 with C3 Glomerulopathy confirmed by a kidney biopsy. They must have low serum C3 levels, been on certain blood pressure medications for at least 90 days, and show specific urine protein levels. Participants need functioning kidneys and vaccinations against certain infections.

What is being tested?

The study tests the effectiveness and safety of iptacopan compared to a placebo in treating Complement 3 Glomerulopathy. It's randomized, meaning participants are put into the iptacopan or placebo group by chance, double-blind so neither researchers nor participants know who gets what treatment.

What are the potential side effects?

While not specified here, common side effects of drugs like iptacopan may include headache, nausea, diarrhea or constipation. More serious risks could involve allergic reactions or potential impact on immune system function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My kidney disease (C3G) was confirmed by a biopsy recently.

Select...

I am between 12 and 60 years old.

Select...

I have been vaccinated against meningitis, and if possible, pneumonia and Haemophilus influenzae.

Select...

My kidney function, measured by GFR, is at least 30 ml/min/1.73m2.

Select...

I am between 18 and 60 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't taken any complement factor inhibitors in the last 6 months.

Select...

My kidney biopsy shows more than 50% scarring.

Select...

My kidney function has declined rapidly, and a biopsy shows significant damage.

Select...

I have been diagnosed with MGUS based on specific blood tests.

Select...

I have had repeated serious infections caused by certain bacteria.

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I haven't taken high-dose steroids or certain immune-suppressing drugs in the last 90 days.

Select...

I have had a cell or organ transplant, including a kidney transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ month 6, month 12 (open-label)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~month 6, month 12 (open-label)

This trial's timeline: 3 weeks for screening, Varies for treatment, and month 6, month 12 (open-label) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)

Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)

Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).

+1 more

Secondary study objectives

Adult cohort: Change from baseline in disease total activity score in a renal biopsy.

Change from baseline in eGFR.

Change from baseline in the FACIT-Fatigue score at 12 months

+8 more

Side effects data

From 2022 Phase 2 trial • 16 Patients • NCT03439839

30%

Pyrexia

20%

Asthenia

20%

Anaemia

20%

Thrombocytopenia

20%

Diarrhoea

20%

Nasopharyngitis

20%

Rhinitis

20%

Foot fracture

20%

Hypertriglyceridaemia

20%

Back pain

20%

Headache

20%

Insomnia

20%

Dysuria

20%

Rhinorrhoea

10%

Escherichia bacteraemia

10%

Basal cell carcinoma

10%

Lymphoproliferative disorder

10%

Squamous cell carcinoma of the oral cavity

10%

Squamous cell carcinoma of the tongue

10%

Haemorrhage intracranial

10%

Penetrating aortic ulcer

10%

Abdominal pain

10%

Abdominal pain upper

10%

Aphthous ulcer

10%

Dysphagia

10%

Nausea

10%

Tongue ulceration

10%

Vomiting

10%

Chest pain

10%

Medical device site irritation

10%

Medical device site pain

10%

Non-cardiac chest pain

10%

Oedema peripheral

10%

Hepatic cytolysis

10%

Ocular icterus

10%

COVID-19

10%

Ear infection

10%

Fungal skin infection

10%

Herpes zoster

10%

Influenza

10%

Oral herpes

10%

Periodontitis

10%

Pyelonephritis

10%

Vaginal infection

10%

Contusion

10%

Vaccination complication

10%

Blood creatine phosphokinase increased

10%

Weight decreased

10%

Hypercholesterolaemia

10%

Hyperferritinaemia

10%

Hyperuricaemia

10%

Vitamin B12 deficiency

10%

Arthralgia

10%

Joint swelling

10%

Musculoskeletal chest pain

10%

Spinal pain

10%

Angiofibroma

10%

Migraine

10%

Paraesthesia

10%

Nightmare

10%

Poor quality sleep

10%

Nocturia

10%

Pollakiuria

10%

Breast pain

10%

Dysmenorrhoea

10%

Genital discomfort

10%

Haematospermia

10%

Vulvovaginal dryness

10%

Cough

10%

Dyspnoea exertional

10%

Upper respiratory tract congestion

10%

Actinic keratosis

10%

Alopecia

10%

Dermatitis acneiform

10%

Dry skin

10%

Ecchymosis

10%

Eczema

10%

Onycholysis

10%

Petechiae

10%

Pruritus

10%

Psoriasis

10%

Andropause

10%

Flushing

10%

Haematoma

10%

Hot flush

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: LNP023 200mg Bid + SoC

Cohort 2: LNP023 50mg Bid + SoC

Cohort 2: LNP023 200mg Bid + SoC

Total

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: iptacopan 200mgExperimental Treatment1 Intervention

iptacopan 200 mg b.i.d.

Group II: Placebo to iptacopan 200mgPlacebo Group1 Intervention

Placebo to iptacopan 200mg b.i.d.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

iptacopan

2018

Completed Phase 2

~20

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Complement 3 Glomerulopathy (C3G) is primarily driven by dysregulation of the alternative complement pathway, leading to excessive deposition of complement proteins in the kidneys. Treatments like Iptacopan, a selective Factor B inhibitor, work by targeting and inhibiting Factor B, a key protein in the alternative pathway. This inhibition reduces the formation of the C3 convertase enzyme, thereby decreasing the activation and deposition of complement proteins that cause kidney damage. By controlling this pathway, these treatments aim to prevent further kidney injury and preserve renal function, which is crucial for improving outcomes in C3G patients.

Control of complement activation in membranous and membranoproliferative glomerulonephritis.Alternative Pathway Is Essential for Glomerular Complement Activation and Proteinuria in a Mouse Model of Membranous Nephropathy.Complement cascade and kidney transplantation: The rediscovery of an ancient enemy.