Dose Escalation of BCX10013 in Subjects With Paroxysmal Nocturnal Hemoglobinuria

Study Overview
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Brief Summary
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This is a multicenter, open-label, intra-subject, dose escalation study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and therapeutic potential of BCX10013 in participants with paroxysmal nocturnal hemoglobinuria (PNH). Approximately 15 participants will be enrolled in this study. Participants may receive treatment for up to 24 weeks.

Official Title
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An Open-Label, Multicenter, Intra-Subject Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Therapeutic Potential of BCX10013 in Subjects With Paroxysmal Nocturnal Hemoglobinuria

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: BCX10013


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or non-pregnant, non-lactating female adults ≥ 18 years old. Documented diagnosis of PNH confirmed by flow cytometry. Body mass index (BMI) ≤ 40 kg/m^2. Are either: (a) naïve to treatment with a complement inhibitor; or (b) have received no treatment with ravulizumab for at least 12 months prior to the screening visit and have received no treatment with eculizumab or pegcetacoplan for 6 months prior to the screening visit. Documentation of current vaccinations against N. meningitidis, S. pneumoniae, and H. influenzae type B [Hib] or willingness to start vaccination series at least 14 days prior to Day 1. Key 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 during the study. Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition, including unstable angina, severe congestive heart failure, unexplained syncope, arrhythmia, and critical aortic stenosis. History of malignancy within 5 years prior to the screening visit. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit. Initiation of treatment with an erythropoiesis-stimulating agent (eg, erythropoietin), a thrombopoietin receptor agonist (eg, eltrombopag), or danazol within 28 days prior to the screening visit. Receiving iron with an unstable dose (ie, increasing or decreasing) in the 28 days prior to the screening visit.

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
Intervention Model: Sequential Assignment
Interventional Model Description: Four dose levels of BCX10013 are planned for escalation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX10013<br>Participants with PNH will receive BCX10013 daily for 4 weeks before dose escalation may occur. | Drug: BCX10013<br>* Four dose levels may be tested in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) and graded laboratory abnormalities, and changes from baseline (CFB) in laboratory analytes, vital signs, electrocardiograms (ECGs), and physical examination findings. |  | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline (CFB) in lactate dehydrogenase |  | Baseline, Week 24 | 
| CFB in the ratio of total PNH red blood cell clone size to PNH white blood cell clone size |  | Baseline, Week 24 | 
| CFB in hemoglobin |  | Baseline, Week 24 | 
| Percentage of participants who are transfusion-free |  | 24 weeks | 
| Percentage of participants achieving a within-subject clinically meaningful CFB in the FACIT-Fatigue Scale |  | 24 weeks | 
| CFB in other clinical biomarkers of PNH disease activity |  | Baseline, Week 24 | 
| Number of participants with clinical PNH symptoms |  | up to 24 weeks | 
| Concentration of BCX10013 and its metabolite(s) in plasma |  | Pre-dose, 0.5, 1, 2, 4, and 6 hours post dose on Day 1, Week 2, and Week 4 | 
| Concentration of BCX10013 and its metabolite(s) in urine (if applicable) |  | Pre-dose and all urine from 0 to 6 hours post dose on Day 1, Week 2, and Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paroxysmal Nocturnal Hemoglobinuria, Factor D, complement inhibitor, alternative pathway inhibitor, BioCryst