Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Interventions
Product Name: BCX9930
Product Code: BCX9930
Pharmaceutical Form: Capsule
INN or Proposed INN: BCX9930
Current Sponsor code: BCX9930
Other descriptive name: BCX9930 hydrochloride
Concentration unit: mg
Sponsors
BioCryst Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent 2. Male or non-pregnant, non-lactating female subjects 3. Subjects who have successfully participated in a previous BCX9930 study of PNH and who experienced a clinical benefit, as confirmed by the Investigator. Successful participation is defined as completion of planned duration of dosing with BCX9930 in the prior study, not inclusive of any extension period. 4. Female participants must meet at least 1 of the following contraception requirements: a. Be a woman of childbearing potential who agrees to use a highly effective contraceptive method throughout the study and for a duration of 30 days after the last dose of study drug. b. Alternatively, true abstinence is acceptable for women of childbearing potential when it is in line with the subject’s preferred and usual lifestyle. c. Be a woman of nonchildbearing potential. 5. Male participants must meet the following contraception requirements: a. Subjects with female partners of childbearing potential must agree to utilize a highly effective contraceptive method. b. Alternatively, true abstinence is acceptable when it is in line with the subject’s preferred and usual lifestyle. 6. In the opinion of the Investigator, the subject is expected to adequately comply with all required study procedures and restrictions for the duration of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Any clinically significant medical or psychiatric condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject’s ability to participate in the study or participation would increase the risk for that subject 2. Any clinically significant history of angina, known coronary artery disease, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, aortic stenosis, or any other cardiovascular abnormality. 3. Chronic systemic corticosteroid use. Note: Topical, inhaled, ocular, or nasal sprays containing corticosteroids are allowed. 4. Investigational drug exposure, other than BCX9930, within 30 days of the baseline visit, or 5.5 half-lives of the investigational drug (whichever is longer) 5. For subjects requiring a screening visit: a. Clinically significant abnormal ECG at the screening visit. This includes, but is not limited to, a QT interval corrected using Fridericia's method (QTcF) > 450 msec in males and > 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. b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) (Exception: Subjects may be enrolled with ALT or AST > 3 × ULN if explained by hemolysis. In these cases, ALT and AST must be 2 x upper limit of normal (ULN) (Exceptions: Subject may be enrolled with total serum bilirubin > 2 x ULN if the elevated bilirubin is explained by hemolysis or in the case of Gilbert’s syndrome. In the case of hemolysis, total serum bilirubin must be < 5 x ULN and in the case of Gilbert’s Syndrome, total bilirubin must be < 7x ULN). 6. Daily use of medications listed in the currently applicable prohibited medications list 7. Pregnant, planning to become pregnant, or having been pregnant within 90 days of baseline, or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess long-term safety and tolerability data in eligible subjects with paroxysmal nocturnal hemoglobinuria (PNH) who previously received BCX9930 in a BioCryst-sponsored study and derived benefit from BCX9930 treatment;Secondary Objective: • To assess the continued effectiveness of BCX9930 in treatment of PNH during long-term administration • To evaluate patient-reported outcomes (PRO) of long-term BCX9930 treatment • To collect PK, PD, and complement biomarker data in subjects with PNH for incorporation into meta-study models of population PK and PK/PD. • To characterize the effects of BCX9930 in subjects with PNH by clinical measurements and PD and complement biomarkers. • To evaluate biomarkers of complement activation during episodes of breakthrough hemolysis (BTH) ;Primary end point(s): Measurement of safety and tolerability by subject incidence of graded treatment-emergent adverse events (TEAEs), laboratory abnormalities, changes to vital signs, electrocardiogram (ECG) results, and physical examination findings;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Clinical PNH symptom assessments including fatigue, dyspnea, chest pain/discomfort, difficulty swallowing (esophageal pain), abdominal pain, headache, erectile dysfunction, hemoglobinuria, jaundice, incidence of BTH, and incidence of thromboembolic events • Clinical measurements of PNH (LDH, hemoglobin, haptoglobin, reticulocytes, transfusion requirements) • PRO endpoints will include scores from the Quality of Life Questionnaire for Patients with Aplastic Anemia/PNH (QLQ-AA/PNH), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, and Treatment Satisfaction Questionnaire for Medication (TSQM). • Concentration of BCX9930 in plasma at steady state in subjects with PNH. • PD and complement biomarker measurements will include PNH red blood cell (RBC) and white blood cell (WBC) clone size, plasma Factor Bb levels and AP activity (as assessed via AP Hemolysis and AP Weislab) ;Timepoint(s) of evaluation of this end point: Week 48 | — |
Countries
European Union, South Africa, United Kingdom
Contacts
Public ContactClinical Operations UK
AMS Advanced Medical Services
Outcome results
None listed