Iptacopan for Paroxysmal Nocturnal Hemoglobinuria

Recruiting at 8 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Anti-C5 therapy

Disqualifiers: Hypersensitivity, Hereditary complement deficiency, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 26 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called iptacopan for children with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood condition that can cause fatigue, shortness of breath, and blood clots. Researchers aim to understand how the body absorbs the drug and ensure its safety for children. The trial includes two groups: one for children aged 12 to under 18 and another for those aged 2 to under 12. Children diagnosed with PNH who are either currently on certain treatments or have specific blood test results might qualify. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anti-C5 therapy, you may switch to iptacopan as part of the study.

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

Research has shown that iptacopan is generally safe for treating paroxysmal nocturnal hemoglobinuria (PNH). Earlier studies found that iptacopan improves hemoglobin levels and reduces the breakdown of red blood cells in patients. Most participants in these studies tolerated iptacopan well, experiencing no severe side effects.

Ongoing research is examining the long-term safety of iptacopan. One study is investigating whether the medication slightly increases the risk of infections. So far, no major safety issues have been reported.

Since iptacopan is being tested in various studies and has shown promising results in adults, there is good reason to believe it will be safe for younger patients too. ^{1 2 3 4 5}

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

Iptacopan is unique because it targets a specific protein in the immune system called factor B, which is involved in the overactive complement system—a key issue in Paroxysmal Nocturnal Hemoglobinuria (PNH). Unlike standard treatments like eculizumab and ravulizumab, which inhibit a different part of the complement system, iptacopan offers a new mechanism of action by blocking an earlier step in the cascade. Researchers are excited about iptacopan because it has the potential to offer more complete protection against red blood cell destruction and might reduce the need for blood transfusions, improving patients' quality of life.

What evidence suggests that iptacopan might be an effective treatment for paroxysmal nocturnal hemoglobinuria?

Research shows that iptacopan effectively treats paroxysmal nocturnal hemoglobinuria (PNH), a condition where red blood cells break down too quickly. Studies have found that iptacopan can increase hemoglobin levels, crucial for carrying oxygen in the blood, and reduce red blood cell breakdown. This often leads to less fatigue and a better quality of life for patients. One study found that after 24 weeks of treatment, the average hemoglobin level was about 13.88 g/dL, which is considered healthy. Iptacopan has been effective both on its own and with other standard treatments. These findings suggest that iptacopan could be a promising option for managing PNH symptoms. Participants in this trial will receive iptacopan, with dosing adjusted based on age and weight. ^{1 5 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 2 to <18 with paroxysmal nocturnal hemoglobinuria (PNH). Eligible participants include those on a stable anti-C5 therapy regimen for at least 6 months, or anti-C5 naive patients with mean hemoglobin <10 g/dL and LDH >1.5× ULN. Vaccination against certain infections is required before starting treatment.

Inclusion Criteria

I've been on a stable anti-C5 therapy for at least 6 months.

I have not used anti-C5 treatments and my hemoglobin level is below 10 g/dL.

My LDH levels are more than 1.5 times the normal limit, confirmed by two tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive iptacopan to assess pharmacokinetics, safety, and tolerability

26 weeks

Visits at Week 2, 4, 12, and 26

Extension Treatment

Continuation of iptacopan treatment to further assess long-term safety and efficacy

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Iptacopan

Trial Overview The study tests iptacopan's pharmacokinetics, safety, and tolerability in treating PNH in children. It's an open-label, single-arm phase 3 trial where all participants receive the same medication without a comparison group.

How Is the Trial Designed?

Group I: LNP023-Cohort 1 (12 < 18 years old) Experimental Treatment 1 Intervention

Participants (12 to \< 18 years old) will take iptacopan at the dose of 200 mg twice per day (in the morning and in the evening).

Group II: LNP023 -Cohort 2 (2 to < 12 years old) Experimental Treatment 1 Intervention

Participants (2 to \< 12 years old) will be dosed based on weight at the Day 1 visit, initially. The study medication dose will be reassessed and re-adjusted as needed based on their weight at Week 12, 26, and 38.

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39323666/

Iptacopan Efficacy and Safety to Treat Paroxysmal ... Iptacopan's effectiveness in improving hemoglobin levels and lowering hemolysis in PNH, both as a monotherapy and in combination with usual treatment.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/8/1816/534949/Patient-reported-improvements-in-paroxysmal

Patient-reported improvements in PNH treated with iptacopan Patients with PNH treated with iptacopan experience meaningful improvement in fatigue and quality of life.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S235230262500081X

Oral iptacopan monotherapy in paroxysmal nocturnal ... The factor B inhibitor iptacopan improved 24-week outcomes in adult patients with paroxysmal nocturnal haemoglobinuria in the phase 3 APPLY-PNH and APPOINT-PNH ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07229235

REAL-CARE: Real-world Effectiveness of Iptacopan in ... This study evaluates iptacopan effectiveness and safety in routine clinical practice, with a focus on hematological response, ...

5. cancernetwork.com cancernetwork.com/view/iptacopan-yields-meaningful-hemoglobin-improvements-in-pretreated-pnh-group

Iptacopan Yields Hemoglobin Improvements in Pretreated PNH Data showed rapid normalization of mean Hb levels following treatment with iptacopan monotherapy. The mean Hb level at week 24 was 13.88 g/dL ( ...

6. ashpublications.org ashpublications.org/blood/article/146/Supplement%201/6538/548935/Efficacy-and-safety-of-iptacopan-in-paroxysmal

Efficacy and safety of iptacopan in paroxysmal nocturnal ... Iptacopan, an oral complement factor B inhibitor, has shown promise in controlled trials, but real-world data on its performance across PNH ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04747613

Study Details | NCT04747613 | Long-term Safety and ... This study is an open-label, single arm, multicenter, roll-over extension study to characterize long-term safety, tolerability and efficacy of iptacopan.

8. catalogues.ema.europa.eu catalogues.ema.europa.eu/node/4358/administrative-details

Post-authorization safety study of iptacopan in adult patients ... The primary objective of the study is to describe the risk of infections due to encapsulated bacteria in patients with PNH treated with ...