BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants Not Receiving Other Complement Inhibitor Therapy

A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria

The purpose of this study was to determine the efficacy and safety of BCX9930 monotherapy for the treatment of adult participants with PNH not currently receiving complement inhibitor therapy.

This was a randomized, placebo-controlled, double-blind, parallel-group, 2-part study. Parts 1 and 2 was to be conducted in the same participants.

Part 1 of the study was designed to evaluate the efficacy, safety, and tolerability of treatment with oral BCX9930 monotherapy for 12 weeks versus placebo in participants with PNH who were not currently receiving treatment with complement inhibitor therapy. Participants were randomized to receive BCX9930 or placebo under double blind conditions for the 12-week randomized treatment period. The primary efficacy and safety analyses were based on Part 1.

Part 2 of the study was designed to evaluate the long-term safety, tolerability, and effectiveness of open-label BCX9930 monotherapy when administered through Week 52. All participants in Part 2 received BCX9930. Participants who were randomized to BCX9930 monotherapy in Part 1 continued to receive BCX9930 in Part 2. Participants who were randomized to placebo in Part 1 discontinued that therapy at the Week 12 visit and received BCX9930 in Part 2.

Inclusion Criteria:

• Male or female, aged ≥ 18 years old
• Body weight ≥ 40 kg
• Documented diagnosis of PNH
• No complement inhibitor therapy for ≥ 12 months prior to screening
• Contraindication to or no access to approved (C3 or C5) complement inhibitor therapies
• Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willingness to start vaccination series
• At screening: PNH clone of ≥ 10%, hemoglobin ≤ 10.5 g/dL and lactate dehydrogenase ≥ 2 × upper limit of normal

Exclusion Criteria:

• Known history of or existing diagnosis of hereditary complement deficiency
• History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation
• Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition
• History of malignancy within 5 years prior to the screening visit
• Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to screening
• Treatment with anti-thymocyte globulin within 180 days prior to screening
• Initiation of treatment with an erythrocyte or platelet growth factor, or danazol within 28 days prior to screening
• Receiving iron supplementation with an unstable dose in the 28 days prior to screening