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

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

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.

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: BCX10013

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Malaysia
  • Ampang, Malaysia
    • BioCryst Investigative Site
• South Africa
  • Bloemfontein, South Africa
    • BioCryst Investigative Site
  • Cape Town, South Africa
    • BioCryst Investigative Site
  • Pretoria, South Africa
    • BioCryst Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCX10013; Participants with PNH will receive BCX10013 daily for 4 weeks before dose escalation may occur.	Drug: BCX10013; Multiple dose levels may be tested in this study.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
CFB in Lactate Dehydrogenase	Baseline, Week 52
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 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
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

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Actual): December 11, 2024
• Study Completion (Actual): December 11, 2024

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Paroxysmal Nocturnal Hemoglobinuria; complement inhibitor; BioCryst; Factor D; alternative pathway inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Proteinuria; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: BCX10013-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No