Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab
Condition: Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: Danicopan; Eculizumab
Intervention description: Participants received a daily oral dose of danicopan TID during the treatment period.; Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
Intervention MeSH terms: Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Four groups will be studied and enrolled sequentially.
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PNH; Paroxysmal Nocturnal Hemoglobinuria; ACH-0144471; Danicopan; Eculizumab; ALXN2040

Summary:

      To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in
      improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan
      dose may be increased within each participant, to a maximum of 200 milligrams (mg) three
      times daily (TID) based on safety and efficacy at protocol-specified time points.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosed with PNH

          -  Have received at least one red blood cell transfusion within last 12 weeks

          -  Anemia with adequate reticulocytosis

          -  Must be on a stable regimen of eculizumab

          -  Platelet count ≥ 40,000/microliter without the need for platelet transfusions

          -  Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and
             Streptococcus pneumoniae or willingness to receive vaccinations based on local
             guidelines

          -  Willingness to receive antibiotic prophylaxis

          -  Female participants must use highly effective birth control to prevent pregnancy
             during the clinical trial and for 30 days after their last dose of study drug

          -  Male participants must use a highly effective birth control with a female partner to
             prevent pregnancy during the clinical trial and for 90 days after the last dose of
             study drug

        Key Exclusion Criteria:

          -  Current evidence of bone marrow failure or aplastic anemia requiring treatment

          -  History of a major organ transplant or hematopoietic stem cell/marrow transplant

          -  Received another investigational agent within 30 days or 5 half-lives of the
             investigational agent prior to study entry, whichever is greater

          -  Documented C5 complement protein mutations

          -  Known or suspected complement deficiency

          -  Contraindication to any of the required vaccinations

          -  Active bacterial infection or clinically significant active viral infection, a body
             temperature >38°C, or other evidence of infection

          -  History of meningococcal infection, or a first-degree relative or household contact
             with a history of meningococcal infection

          -  History of hypersensitivity reactions to commonly used antibacterial agents

        Note: Additional inclusion/exclusion criteria may apply, per protocol.