Dose Escalation of BCX10013 in Subjects With Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06100900
• Other study ID #: BCX10013-105
• Status: Recruiting
• Phase: Phase 1
• Start date: October 24, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: March 2024
• Source: BioCryst Pharmaceuticals
• Contact: BioCryst Pharmaceuticals, Inc.
• Phone: 919.859.1302
• Email: clinicaltrials[@]biocryst.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 paroxysmal nocturnal hemoglobinuria (PNH). Approximately 15 participants will be enrolled in this study. Participants may receive treatment for up to 24 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• BCX10013
Four dose levels may be tested in this study.

Locations

Country	Name	City	State
Malaysia	BioCryst Investigative Site	Ampang
South Africa	BioCryst Investigative Site	Bloemfontein
South Africa	BioCryst Investigative Site	Cape Town
South Africa	BioCryst Investigative Site	Pretoria

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

Malaysia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline (CFB) in lactate dehydrogenase		Baseline, Week 24
Secondary	CFB in the ratio of total PNH red blood cell clone size to PNH white blood cell clone size		Baseline, Week 24
Secondary	CFB in hemoglobin		Baseline, Week 24
Secondary	Percentage of participants who are transfusion-free		24 weeks
Secondary	Percentage of participants achieving a within-subject clinically meaningful CFB in the FACIT-Fatigue Scale		24 weeks
Secondary	CFB in other clinical biomarkers of PNH disease activity		Baseline, Week 24
Secondary	Number of participants with clinical PNH symptoms		up to 24 weeks
Secondary	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
Secondary	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