Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment
Condition: Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH terms: Hemoglobinuria; Anemia; Hemoglobinuria, Paroxysmal
Intervention: LNP023; Eculizumab; Ravulizumab
Intervention description: Taken Orally b.i.d. Dosage Supplied: 200 mg Dosage form: Hard gelatin capsule Route of Administration: Oral; Administered as intravenous infusion every 2 weeks as per the stable regimen, the maintenance dose is a fixed dose.
Dosage Supplied: 300 mg/30mL Dosage form: Concentrate solution for infusion; Administered as intravenous infusion every 8 weeks, the maintenance dose is based on body weight.
Dosage Supplied: 300 mg/30mL Dosage form: Concentrate solution for infusion
Intervention MeSH terms: Eculizumab; Ravulizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Paroxysmal nocturnal hemoglobinuria; Hemoglobin; Anemia; LNP023; eculizumab; ravulizumab

Summary:

      This study was a multi-center, randomized, open-label, active comparator-controlled, parallel
      group study.

      The purpose of this Phase 3 study in PNH patients presenting with residual anemia despite
      treatment with anti-C5 antibody, was to determine whether iptacopan is efficacious and safe
      for the treatment of PNH through demonstration of superiority of iptacopan compared to
      anti-C5 antibody treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by
             high-sensitivity flow cytometry with clone size ≥ 10%

          -  Stable regimen of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at
             least 6 months prior to randomization

          -  Mean hemoglobin level <10 g/dL

          -  Vaccination against Neisseria meningitidis infection is required prior to the start of
             treatment.

          -  If not received previously, vaccination against Streptococcus pneumoniae and
             Haemophilus influenzae infections should be given

        Exclusion Criteria:

          -  Participants on a stable eculizumab dose but with a dosing interval of 11 days or less
             or patients on stable ravulizumab dose but with a dosing interval of less than 8
             weeks.

          -  Known or suspected hereditary complement deficiency at screening

          -  History of hematopoietic stem cell transplantation

          -  Patients with laboratory evidence of bone marrow failure (reticulocytes <100x10E9/L;
             platelets <30x10E9/L; neutrophils <500x10E6/L).

          -  Active systemic bacterial, viral (incl. COVID-19), or fungal infection within 14 days
             prior to study drug administration

          -  A 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., eGFR < 30 mL/min/1.73 m2, dialysis), advanced cardiac disease (e.g., NYHA class
             IV), 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.