BCX9930 for the Treatment of PNH in Subjects Not Receiving Other Complement Inhibitor Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of BCX9930 monotherapy for the treatment of adult patients with PNH not currently receiving complement inhibitor therapy.

Detailed Description
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This is a randomized, placebo-controlled, double-blind, parallel-group, 2-part study. Parts 1 and 2 will be conducted in the same subjects. Part 1 of the study is designed to evaluate the efficacy, safety, and tolerability of treatment with oral BCX9930 monotherapy for 12 weeks versus placebo in subjects with PNH who are not currently receiving treatment with complement inhibitor therapy. Subjects will be randomized to receive BCX9930 or placebo under double blind conditions for the 12-week randomized treatment period. The primary efficacy and safety analyses will be based on Part 1. Part 2 of the study is designed to evaluate the long-term safety, tolerability, and effectiveness of open-label BCX9930 monotherapy when administered through Week 52. All subjects in Part 2 will receive BCX9930. Subjects who are randomized to BCX9930 monotherapy in Part 1 will continue to receive BCX9930 in Part 2. Subjects who are randomized to placebo in Part 1 will discontinue that therapy at the Week 12 visit and receive BCX9930 in Part 2.

Official Title
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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 PNH

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: BCX9930 monotherapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX9930 monotherapy<br>In Part 1, participants are randomized to 2:1 to receive BCX9930 monotherapy or placebo under double-blind conditions In Part 2, all participants receive open-label BCX9930 monotherapy | Drug: BCX9930 monotherapy<br>* Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily<br>|
| Placebo Comparator: Placebo<br>In Part 1, participants are randomized to 2:1 to receive BCX9930 monotherapy or placebo under double-blind conditions | Drug: Placebo<br>* Administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in hemoglobin | Change from baseline in hemoglobin | at Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who are transfusion-free | Proportion of subjects who are transfusion-free | from Week 4 to Week 12 | 
| Number of units of packed red blood cells transfused | Number of units of packed red blood cells transfused | from Week 4 to Week 12 | 
| Percent change from baseline in lactate dehydrogenase | Percent change from baseline in lactate dehydrogenase | at Week 12 | 
| Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale score | Change from baseline in FACIT-Fatigue scale score; FACIT-Fatigue total scale score ranges from 0 to 52, with a higher score indicating less fatigue | at Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCX9930, factor D inhibitor, proximal complement inhibitor, oral therapy, paroxysmal nocturnal hemoglobinuria