What side effects are associated with this type of intervention?

Complement inhibitors used in the treatment of Atypical Hemolytic Uremic Syndrome (aHUS), such as eculizumab, can cause side effects including increased susceptibility to infections (especially meningococcal infections), headache, hypertension, gastrointestinal disturbances, and infusion-related reactions. As iptacopan is also a complement inhibitor, it is expected to have a similar side effect profile, though specific data on iptacopan's side effects would need further clinical validation.

What prior FDA approvals exist?

The FDA has previously approved eculizumab (Soliris) and ravulizumab (Ultomiris) for the treatment of atypical hemolytic uremic syndrome (aHUS). Both drugs are complement inhibitors that target the C5 protein, preventing the formation of the membrane attack complex and thereby reducing hemolysis, thrombocytopenia, and renal impairment associated with aHUS. These treatments are similar to Iptacopan, which is also a complement inhibitor, though it targets a different component of the complement pathway.

What other types of research exist?

Promising novel alternatives to Iptacopan for aHUS patients in 2024 include pegcetacoplan and eculizumab. Pegcetacoplan, a C3 inhibitor, has shown efficacy in clinical trials for complement-mediated diseases. Eculizumab, a C5 inhibitor, is already established in treating similar conditions and may offer benefits for aHUS patients.

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Complement Inhibitor

Iptacopan for Atypical Hemolytic Uremic Syndrome (APPELHUS 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

Adult patients with evidence of thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury

Be older than 18 years old

Must not have

Liver disease or liver injury at screening

Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 52 weeks of study treatment

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing iptacopan, a new medication, in adults with a rare disease called aHUS. The drug aims to calm an overactive part of their immune system to improve their health.

Who is the study for?

Adults with atypical Hemolytic Uremic Syndrome (aHUS) who haven't been treated with complement inhibitors can join. They must have vaccinations against certain infections or take antibiotics if the vaccine was recent. People can't join if they've had certain treatments for aHUS, other kidney diseases, severe infections including COVID-19, or immune system disorders like lupus.

What is being tested?

The trial is testing Iptacopan's effectiveness and safety in treating aHUS in adults new to complement inhibitor therapy. It's a Phase 3 study which means it’s closer to potentially being approved for general use if successful.

What are the potential side effects?

While specific side effects of Iptacopan are not listed here, similar medications may cause reactions at the injection site, headaches, nausea, or increase the risk of infections due to immune system suppression.

Eligibility Criteria

Inclusion Criteria

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

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I have TMA, including low platelet count, blood cell destruction, and kidney issues.

Exclusion Criteria

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

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I have liver disease or injury.

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I have had a transplant involving bone marrow, heart, lung, small bowel, pancreas, or liver.

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I have HUS due to drug exposure or specific genetic conditions.

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My kidney issues are not due to aHUS or chronic failure, nor do I have a family history of genetic kidney diseases not related to the immune system.

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I do not have severe infections, COVID-19, or a history of serious bacterial infections.

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I have a very low ADAMTS13 activity, or STx-HUS, or a positive direct Coombs test.

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I am currently taking medication that affects my immune system.

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I am on long-term dialysis.

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I have scleroderma, lupus, or antiphospholipid syndrome.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 52 weeks of study treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~52 weeks of study treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 52 weeks of study treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Long term safety and efficacy evaluations

Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody

Secondary study objectives

Change from baseline in chronic kidney disease (CKD) stage

Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire

Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Iptacopan 200 mg b.i.dExperimental Treatment1 Intervention

Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Iptacopan

2021

Completed Phase 1

~40

0 / 10Eligibility 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 inhibitors, such as those being studied like iptacopan, target specific components of the complement system to prevent its uncontrolled activation, which is a key factor in the pathogenesis of Atypical Hemolytic Uremic Syndrome (aHUS). By inhibiting parts of the complement pathway, these treatments prevent endothelial damage, hemolysis, and thrombosis, which are critical in reducing kidney injury and improving outcomes for aHUS patients.