Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
Paroxysmal Nocturnal Hemoglobinuria, Factor D, complement inhibitor, alternative pathway inhibitor, BioCryst
Brief summary
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 PNH. Approximately 8 participants will be enrolled in this study. Participants may receive treatment for up to 52 weeks.
Interventions
DRUGBCX10013
Multiple dose levels may be tested in this study.
Sponsors
BioCryst Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multiple dose levels of BCX10013 are planned for escalation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or non-pregnant, non-lactating female adults ≥ 18 years old. 2. Documented diagnosis of PNH confirmed by flow cytometry. 3. Body mass index (BMI) ≤ 40 kg/m\^2. 4. 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. 5. 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
1. Known history of or existing diagnosis of hereditary complement deficiency. 2. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation during the study. 3. 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. 4. History of malignancy within 5 years prior to the screening visit. 5. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit. 6. 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. 7. Receiving iron with an unstable dose (ie, increasing or decreasing) in the 28 days prior to the screening visit.
Design outcomes
Primary
| Measure | 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 52 weeks |
Secondary
| Measure | Time frame |
|---|---|
| CFB in the Ratio of Total PNH Red Blood Cell Clone Size to PNH White Blood Cell Clone Size | Baseline, Week 52 |
| CFB in Hemoglobin | Baseline, Week 52 |
| Percentage of Participants who are Transfusion-free | 52 weeks |
| Percentage of Participants Achieving a Within-subject Clinically Meaningful CFB in the FACIT-Fatigue scale | 52 weeks |
| CFB in Lactate Dehydrogenase | Baseline, Week 52 |
| Number of Participants with Clinical PNH Symptoms | up to 52 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 |
| CFB in Other Clinical Biomarkers of PNH Disease Activity including absolute reticulocyte count, total PNH red blood cell clone size, haptoglobin levels, total bilirubin, and aspartate transaminase | Baseline, Week 52 |
Countries
Malaysia, South Africa
Outcome results
None listed