Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy

A Multicenter, Single-arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy

The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.

This study was a multicenter, single-arm, open-label trial which was comprised of 8 weeks screening period, 24-week core treatment period and 24-week extension treatment period.

Eligible PNH patients with hemolysis (LDH > 1.5 ULN) and anemia (hemoglobin <10 g/dL), who were naive to complement inhibitor therapy, including anti-C5 antibody treatment, received iptacopan monotherapy at a dose 200 mg orally b.i.d.

Inclusion Criteria:

• Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with RBCs and WBCs clone size ≥ 10%
• Mean hemoglobin level <10 g/dL
• LDH > 1.5 x Upper Limit of Normal (ULN)
• Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment
• If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given

Exclusion Criteria:

• Prior treatment with a complement inhibitor, including anti-C5 antibody
• Known or suspected hereditary complement deficiency
• History of hematopoietic stem cell transplantation
• Patients with laboratory evidence of bone marrow failure (reticulocytes <100x109/L; platelets <30x109/L; neutrophils <0.5x109/L).
• Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration.
• History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus.
• Major concurrent comorbidities including but not limited to severe kidney disease (e.g., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.