Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.

Study Overview
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Brief Summary
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The purpose of the study is to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switch from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.

Detailed Description
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This is a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients. This study is comprised of two periods: A Screening period lasting up to 8 weeks. A 24-week open-label, iptacopan Treatment period. After completion of the treatment period, participants who continue to benefit from the iptacopan treatment based on the study doctor's evaluation will be able to join the Roll-over extension study.

Official Title
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A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: Iptacopan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician. Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening Mean hemoglobin level ≥10 g/dL Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment. If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations. Ability to communicate well with the investigator, to understand and comply with the requirements of the study Other protocol -defined inclusion criteria may apply at the end. Exclusion Criteria: Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening History of stem cell transplantation or any solid organ transplantation Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening) A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening. History of cancer of any part of the body within the past 5 years, Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial. Any medical condition deemed likely to interfere with the patient's participation in the study Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A multicenter, single arm, open-label trial to evaluate efficacy and safety of oral, twice daily iptacopan in adult PNH patients who have Hb≥10 g/dL in response to anti-C5 antibody and switch to iptacopan
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iptacopan treatment in adult PNH patients<br>Subjects will receive iptacopan at a dose of 200 mg b.i.d. orally | Drug: Iptacopan<br>* Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan | To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC | Up to 168 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hb levels to demonstrate superiority of iptacopan | To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC | Up to 168 days | 
| Percentage of hematological responders to iptacopan treatment | Percentage of hematological responders to iptacopan treatment will be collected | Up to 168 days | 
| Change from baseline in Absolute Reticulocytes count (ARC) levels | To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH). | Up to 168 days | 
| Percentage change from baseline in lactate dehydrogenase (LDH) levels | To assess the effect of iptacopan on markers of EVH and IVH. | Up to 168 days | 
| Change in treatment satisfaction score using TSQM-9 questionnaire | TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher representing better scores for the domain. | Up to 168 days | 
| Change in fatigue score using FACIT-F questionnaire | The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-Fatigue scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. | Up to 168 days | 
| Rate of Breakthrough hemolysis (BTH) | Occurrence of BTH reported from D1 to D168 | 24 weeks | 
| Rate of Major Adverse Vascular Events (MAVEs) | Occurrence of MAVEs reported from D1 to D168 | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paroxysmal Nocturnal Hemoglobinuria, iptacopan, single arm open-label, Hb≥10 g/dL in response to anti-C5 antibody, switch to iptacopan, PNH, LNP023