Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab

A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy

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.

The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH.

The 24-week treatment period was followed by a long-term extension phase. In the extension phase, participants received the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase.

Results are reported for the 24-week treatment period.

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.