BCX9930 for Treatment of PNH in Subjects With Inadequate Response to C5 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 PNH compared to continued C5 inhibitor therapy in adult PNH patients with residual anemia despite treatment with a C5 inhibitor.

Detailed Description
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This is a randomized, active comparator-controlled, open-label, 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 oral BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in subjects with PNH with inadequate response to their current C5 inhibitor therapy. Subjects will be randomized to either discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor therapy for the 24-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 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 C5 inhibitor therapy in Part 1 will discontinue that therapy at the Week 24 visit and receive BCX9930 in Part 2.

Official Title
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A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: BCX9930
* Drug: Eculizumab
* Drug: Ravulizumab


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 Currently being treated with a stable C5 inhibitor regimen Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willing to start vaccination series At screening: PNH clone size of ≥ 10% and hemoglobin ≤ 10.5 g/dL 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX9930 monotherapy<br>In Part 1, participants are randomized 2:1 to receive BCX9930 monotherapy or continue with current C5 inhibitor In Part 2, all subjects receive BCX9930 monotherapy | Drug: BCX9930<br>* Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily<br>|
| Active Comparator: Continued C5 inhibitor therapy<br>In Part 1, participants are randomized 2:1 to receive BCX9930 monotherapy or continue with current C5 inhibitor | Drug: Eculizumab<br>* Administered by intravenous infusion per current dose regimen<br>* Other names: Soliris;Drug: Ravulizumab<br>* Administered as intravenous infusion per current dose regimen<br>* Other names: Ultomiris, ALXN1210, ravulizumab-cwvz;|

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 | mean of values at Weeks 12, 16, 20, and 24 | 

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 24 | 
| Number of units of packed red blood cells transfused | Number of units of packed red blood cells transfused | from Week 4 to Week 24 | 
| 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 | mean of values at Weeks 12, 16, 20, and 24 | 

 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, inadequate response to C5 inhibitor, C5 inhibitor, eculizumab, ravulizumab