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Dose Escalation of BCX10013 in Participants with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Phase 1
Completed
Conditions
Paroxysmal Nocturnal Hemoglobinuria
Interventions
Registration Number
NCT06100900
Lead Sponsor
BioCryst Pharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
BCX10013BCX10013Participants with PNH will receive BCX10013 daily for 4 weeks before dose escalation may occur.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
CFB in Lactate DehydrogenaseBaseline, Week 52
CFB in the Ratio of Total PNH Red Blood Cell Clone Size to PNH White Blood Cell Clone SizeBaseline, Week 52
CFB in HemoglobinBaseline, Week 52
Percentage of Participants who are Transfusion-free52 weeks
Percentage of Participants Achieving a Within-subject Clinically Meaningful CFB in the FACIT-Fatigue scale52 weeks
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 transaminaseBaseline, Week 52
Number of Participants with Clinical PNH Symptomsup to 52 weeks
Concentration of BCX10013 and its Metabolite(s) in PlasmaPre-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

Trial Locations

Locations (1)

BioCryst Investigative Site

🇿🇦

Pretoria, South Africa

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