A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects with Inadequate Response to C5 Inhibitor Therapy

Phase 2

Withdrawn

• Conditions: paroxysmal nocturnal hemoglobinuria; PNH; 10038158

• Registration Number: NL-OMON51609
• Lead Sponsor: BioCryst Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

1. Male or female, aged >= 18 years old.
2. Body weight >= 40 kg.
3. Documented diagnosis of PNH confirmed by flow cytometry with a PNH
granulocyte or monocyte clone size of >= 10% during screening.
4. Treated with a stable regimen of eculizumab for >= 3 months prior to the
screening visit or ravulizumab for >= 6 months prior to the screening visit.
5. Recorded the following results during screening:
a. Hb of <= 105 g/L (<= 10.5 g/dL).
b. ARC of >= 100 × 10^9 cells/L (>= 100,000 cells/µL; >= 100 G/L).
c. Absolute neutrophil count of >= 0.75 × 10^9 cells/L (>= 750 cells/µL; >= 0.75 ×
G/L).
d. Platelet count of >= 30 × 10^9/L (>= 30,000/µL; >= 30 G/L).
e. Adequate iron reserve based on ferritin >= LLN or total iron binding capacity
<= upper limit of the normal reference range (ULN).
f. Estimated glomerular filtration rate of >= 60 mL/min/1.73 m2 using the
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey and
Stevens 2010).
6. Contraception requirements: WOCBP and partners of male subjects to use
highly effective contraception
7. Documentation of current vaccinations against Neisseria meningitidis types
A, C, W, and Y, and Streptococcus pneumoniae, or willingness to start
vaccination series at least 14 days prior to Day 1.
(Note: Vaccination for N. meningitidis type B and for H. influenzae type B
(Hib) is strongly encouraged where authorized and available.)
8. In the opinion of the investigator, the subject is expected to adequately
comply with all required study procedures and restrictions for the study,
including compliance with the BID dosing schedule for BCX9930.
9. Willing and able to provide written informed consent

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, with
exception of adequately treated non-melanoma skin or superficial bladder
cancer, curatively treated carcinoma in situ of the cervix, or other curatively
treated solid tumor deemed by the investigator and medical monitor to be at low
risk for recurrence.
5. Active bacterial, viral, or fungal infection or any other serious infection
within 14 days prior to screening.
(Note: Suspected or confirmed coronavirus disease [COVID-19]; persistent or
recurrent positive test(s) for severe acute respiratory syndrome coronavirus 2
[SARS-CoV-2] nucleic acids or antigens; and worsening of dyspnea not due to
PNH, vasculitic rash, and persistent fever or other symptoms consistent with
multisystem inflammatory syndrome in adults [MIS A] are exclusionary.)
6. Current participation in any other investigational drug study or
participation in an investigational drug study within 30 days prior to the
screening visit, or 5.5 half-lives of the investigational drug, whichever is
longer.
7. Treatment with anti-thymocyte globulin within 180 days prior to the
screening visit.
8. 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.
(Note: Treatment with these medications initiated > 28 days prior to the
screening visit is not exclusionary, if the dose is stable and there is a
reasonable expectation that treatment will be continued.)
9. Receiving iron supplementation with an unstable dose in the 28 days prior to
the screening visit.
10. Clinically significant abnormal electrocardiogram (ECG) at the screening
visit.
(Note: This includes, but is not limited to, a QT interval corrected using
Fridericia*s method [QTcF] of > 450 msec in males or > 470 msec in females, or
ventricular and/or atrial premature contractions that are more frequent than
occasional, and/or as couplets or higher in grouping.)
11. Subjects with any of the following results at the screening visit:
a. Alanine aminotransferase (ALT; also serum glutamic-pyruvic transaminase
[SGPT]) >3 × ULN.
b. Aspartate aminotransferase (AST; also serum glutamic-oxaloacetic
transaminase [SGOT]) >3 × ULN.
(Note: Subjects may be enrolled with AST >3 × ULN if explained by hemolysis.)
c. Total serum bilirubin >2 × ULN
(Note: Subjects may be enrolled with total serum bilirubin >2 × ULN if
explained by hemolysis or Gilbert*s syndrome. In the case of hemolysis, total
serum bilirubin must be <5 × ULN and in the case of Gilbert*s syndrome, total
serum bilirubin must be <11 × ULN.)
12. Current use of a prohibited concomitant medication within 7 days prior to
Day 1 as detailed in Section 9.8.1.
13. Positive serology for

Study & Design

• Study Type: Interventional
• Study Design: Not specified