Clinical trial NCT06100900: Dose Escalation of BCX10013 in Participants with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Paroxysmal Nocturnal Hemoglobinuria
Factor D
complement inhibitor
alternative pathway inhibitor
BioCryst
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-10-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Multiple dose levels of BCX10013 are planned for escalation.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: up to 52 weeks
Secondary outcomes:
measure: CFB in Lactate Dehydrogenase
timeFrame: Baseline, Week 52
measure: CFB in the Ratio of Total PNH Red Blood Cell Clone Size to PNH White Blood Cell Clone Size
timeFrame: Baseline, Week 52
measure: CFB in Hemoglobin
timeFrame: Baseline, Week 52
measure: Percentage of Participants who are Transfusion-free
timeFrame: 52 weeks
measure: Percentage of Participants Achieving a Within-subject Clinically Meaningful CFB in the FACIT-Fatigue scale
timeFrame: 52 weeks
measure: 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
timeFrame: Baseline, Week 52
measure: Number of Participants with Clinical PNH Symptoms
timeFrame: up to 52 weeks
measure: Concentration of BCX10013 and its Metabolite(s) in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post dose on Day 1, Week 2, and Week 4
measure: Concentration of BCX10013 and its Metabolite(s) in Urine (if applicable)
timeFrame: Pre-dose and all urine from 0 to 6 hours post dose on Day 1, Week 2, and Week 4
Other outcomes:
Locations:
city: Ampang
country: Malaysia
facility: BioCryst Investigative Site
city: Bloemfontein
country: South Africa
facility: BioCryst Investigative Site
city: Cape Town
country: South Africa
facility: BioCryst Investigative Site
city: Pretoria
country: South Africa
facility: BioCryst Investigative Site
Study officials:
References: