Long-term Safety and Tolerability of Iptacopan in Patients With Paroxysmal Nocturnal Hemoglobinuria

Study Overview
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Brief Summary
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This study is an open-label, single arm, multicenter, roll-over extension study to characterize long-term safety, tolerability and efficacy of iptacopan and to provide access to iptacopan to patients with PNH who have completed Novartis-sponsored Phase 2 or 3 studies with iptacopan

Detailed Description
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The purpose of this phase 3 open-label, single arm, multicenter study is to evaluate the long-term safety, tolerability and efficacy of iptacopan in patients with PNH and to provide access to patients who have completed (without tapering down) Phase 2 and Phase 3 trials and derived benefit from iptacopan treatment.

Official Title
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An Open Label, Multicenter Roll-over Extension Program (REP) to Characterize the Long-term Safety and Tolerability of Iptacopan (LNP023) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Completed PNH Phase 2 and Phase3 Studies With 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: Male and female participants ≥ 18 years of age with a diagnosis of PNH who have completed the treatment extension period (without tapering down) of Phase II iptacopan studies (CLNP023X2204, CLNP023X2201), Period 4 of LFG316X2201 or Phase III (CLNP023C12302 and CLNP023C12301) clinical studies at the time point of enrollment visit in this roll over extension. Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections Per investigator's clinical judgement benefit from continued treatment with iptacopan and has been clinically stable on iptacopan monotherapy for at least 3 months Exclusion Criteria: Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the investigator, could put the subject at increased risk or potentially confound study data. History of recurrent invasive infections caused by encapsulated organisms, such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae History of hematopoietic stem cell transplantation Other protocol-defined inclusion/exclusion criteria may apply.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iptacopan<br>Participants will be receiving open label oral iptacopan 200 mg b.i.d monotherapy | Drug: Iptacopan<br>* Taken orally b.i.d. Dosage supplied: 200 mg Dosage form: hard gelatin capsule Route of administration: oral<br>* Other names: LNP023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with adverse events | Safety evaluations including but not limited to adverse events/serious adverse events, safety laboratory parameters, vital signs, etc. through End of Study visit | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions | Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions evaluated over yearly intervals | 60 months | 
| Proportion of participants who remain free from transfusions | Proportion of participants who remain free from transfusions evaluated over yearly intervals | 60 months | 
| Rate of breakthrough hemolysis (BTH) | Rate of breakthrough hemolysis (BTH) | 60 months | 
| Proportion of participants with Major Adverse Vascular Events MAVEs | MAVEs (incl. thrombosis) evaluated over yearly intervals | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iptacopan, Paroxysmal Nocturnal Hemoglobinuria (PNH), Hemoglobin, Anemia, LNP023