Study to Assess the Pharmacokinetics, Safety, and Tolerability of Iptacopan in Pediatric PNH Patients

This is a multicenter, open-label, single arm study comprised of an up to a 8-week Screening Period, and a 26-week Treatment Period followed by a 26-week Extension Treatment Period.

This study will enroll a minimum of 12 pediatric patients 2 to < 18 years of age in a staggered manner into 3 cohorts: Cohort 1 (adolescents 12 to < 18 years of age, approximately 6 patients), Cohort 2a (6 to < 12 years of age, approximately 4 patients), and Cohort 2b (2 to < 6 years of age, approximately 2 patients).

Inclusion criteria

• Male and female participants 2 to < 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with red blood cells (RBCs) and with white blood cells granulocytes/monocytes clone size ≥ 10%. The minimum body weight for patients in Cohort 1 is 35 kg.
• Patients being treated with anti-C5 therapy and who have been on a stable regimen (dose and interval) for at least 6 months prior to enrollment, may be screened and enrolled in the study and switched to iptacopan irrespective of their anemia and hemolysis status, at the discretion of the Principal Investigator.
• Patients who are anti-C5 treatment naive: mean hemoglobin level < 10 g/dL confirmed by central laboratory assessment during screening.
• Patients who are anti-C5 treatment naive: lactate dehydrogenase (LDH) > 1.5 × upper limit of normal (ULN) documented by at least 2 laboratory measurements 2 to 6 weeks apart during the screening period, one of which is to be done by the central lab.
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
• Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before iptacopan.

Exclusion criteria

• History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
• Known or suspected hereditary complement deficiency at screening.
• History of hematopoietic stem cell transplantation (HSCT) or scheduled for HSCT within 52 weeks from enrollment into the study (Day 1).
• Patients with laboratory evidence of bone marrow failure (reticulocytes < 100 x 10 to the ninth/L; platelets < 30 × 10 to the ninth/L; neutrophils < 0.5 × 10 to the ninth/L).
• Active systemic bacterial, viral (including COVID-19), or fungal infection within 14 days prior to study drug administration.
• Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration.

Other protocol-defined inclusion/exclusion criteria may apply.