First-in-Human Study of BCX9930 in Healthy Volunteers and Patients With PNH
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Drug: Placebo
- Registration Number
- NCT04330534
- Lead Sponsor
- BioCryst Pharmaceuticals
- Brief Summary
This is a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX9930 in healthy subjects and in subjects with paroxysmal nocturnal hemoglobinuria (PNH; Part 3). Pharmacokinetics is an analysis of how the body handles the study drug BCX9930 and pharmacodynamics is an analysis of the activity that the study drug BCX9930 may have in the body.
- Detailed Description
Up to 6 sequential ascending dose cohorts are planned to be dosed in a sequential manner in Part 1 of the study. Eight subjects will be treated with a single dose of the study drug per dose cohort (6 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.
Up to 7 ascending, multiple dose cohorts will be enrolled in a sequential manner in Part 2 of the study. In Cohorts 1 through 3, twelve subjects will be treated with either a 7-day or 14-day course of study drug (10 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo) administered orally. In Cohorts 4 through 7, twelve subjects will be treated with a 3-day course of study drug (10 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo) administered orally. The daily dose may be split into 2 times daily (BID) or 3 times daily (TID) dosing for the multiple ascending dose part as needed. Escalation to the next higher dose level in Part 2 will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.
Part 3 of the study consists of up to 2 sequential ascending multiple dose cohorts of up to 8 subjects; each cohort may enroll up to 4 subjects with PNH who are naïve to both eculizumab and ravulizumab and up to 4 subjects with PNH who are currently being treated with either eculizumab or ravulizumab. In each cohort, subjects will receive one daily dose of BCX9930 on Days 1 to 14 and a higher daily dose on Days 15 to 28. Cohort 2 will start after independent data monitoring committee (DMC) review of Cohort 1 data and communication of their evaluation to Part 3 investigators. In South Africa, subjects that have clinical benefit from BCX9930 will be allowed to continue dosing for up to 48 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 168
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BCX9930 BCX9930 Parts 1, 2 and 3 Placebo Placebo Parts 1 and 2 only
- Primary Outcome Measures
Name Time Method Change from baseline in temperature Part 3: Day 44 or Week 50 (South Africa only) Change from baseline in respiratory rate Part 3: Day 44 or Week 50 (South Africa only) Change in Electrocardiogram (PR interval) Part 3: Day 44 or Week 50 (South Africa only) Change in Electrocardiogram (QRS interval) Part 3: Day 44 or Week 50 (South Africa only) Incidence of graded treatment-emergent adverse events Part 3:Day 44 or Week 50 (South Africa only) Incidence of graded urinalysis abnormalities Part 3: Day 44 or Week 50 (South Africa only) Change from baseline in heart rate Part 3: Day 44 or Week 50 (South Africa only) Incidence of graded laboratory chemistry abnormalities Part 3:Day 44 or Week 50 (South Africa only) Incidence of graded coagulation abnormalities Part 3: Day 44 or Week 50 (South Africa only) Incidence of graded hematology abnormalities Part 3: Day 44 or Week 50 (South Africa only) Change from baseline in blood pressure Part 3: Day 44 or Week 50 (South Africa only) Change in Electrocardiogram (RR interval) Part 3:Day 44 or Week 50 (South Africa only) Change in Electrocardiogram (QT interval) Part 3:Day 44 or Week 50 (South Africa only)
- Secondary Outcome Measures
Name Time Method Plasma BCX9930 AUCinf plasma PK parameters are based on blood sampling through Day 4 for Part 1 Plasma BCX9930 Cmax plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3 Plasma BCX9930 Tmax plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3 Plasma BCX9930 t1/2 plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3 Plasma BCX9930 AUCtau plasma PK parameters are based on blood sampling through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3 Serum AP complement activity Part 1:through Study Day 4; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and Part 3 through Day 28 or Week 48 (South Africa only) Plasma Factor Bb Part 1:through Study Day 4; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and Part 3 through Day 28 or Week 48 (South Africa only) Number of blood transfusions Part 3:baseline through Day 28 or Week 50 (South Africa only) Lactate dehydrogenase Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only) Hemoglobin Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only) Absolute reticulocyte count Part 3: values and change from baseline through Day 28 or Week 50 (South Africa only) Haptoglobin Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only)
Trial Locations
- Locations (1)
Study Site
🇬🇧London, United Kingdom