complement 3 glomerulopathy immunoglobulin A nephropathy primary membranous nephropathy MedDRA version: 20.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 21.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: PT Classification code 10077827 Term: C3 glomerulopathy System Organ Class: 10038359 - Rena
Conditions
Sponsors
BioCryst Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent 2. Male or non-pregnant, non-lactating female subjects = 18 years of age 3. Body weight = 40 kg. 4. Primary diagnosis of C3G, IgAN, or PMN confirmed by central pathology review of digital images and pathology reports of renal biopsy samples 5. For subjects with C3G only, documentation of duration of illness of at least 90 days by either a prior biopsy collected = 90 days prior to screening confirming a diagnosis of C3G OR a clinical diagnosis of C3G with at least one documented proteinuria assessment = 90 days prior to initial screening visit. 6. For subjects with C3G only, proteinuria defined as = 1 g of urinary protein per 24 hours at screening that has not shown a = 25% decrease from the most recent documented proteinuria assessment, which was collected = 30 days prior to and = 180 days of initial screening visit. 7. For subjects with IgAN only, proteinuria defined as 1 g to = 4 g of urinary protein per 24 hours at screening that has not shown a = 25% decrease from the most recent documented proteinuria assessment, which was collected = 30 days prior to and = 180 days of initial screening visit. 8. For subjects with PMN only, an anti-phospholipase A2 receptor antibody (aPLA2Rab) Immunoglobulin G (IgG) titer of = 150 U/mL and 3.5 g to =11 g of urinary protein per 24 hours at screening that has not shown a = 25% decrease from the most recent documented proteinuria assessment, which was collected = 30 days prior to and = 180 days of initial screening visit. 9. An eGFR = 50 mL/min/1.73 m2 (or = 30 mL/min/1.73 m2 after DMC recommendation) 10. Resting supine vital signs within the following ranges: • Systolic blood pressure, 80 to 150 mm Hg, inclusive, for adults • Systolic blood pressure below the 90th percentile, for adolescents per Section 12.10.1 • Diastolic blood pressure = 90 mm Hg 11. Treatment with a stable, maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 60 days prior to the Day 1 12. Contraception requirements - WOCBP and female partners of male subjects to use highly effective contraception methods 13. Documentation of current vaccination against N. meningitidis Types A, C, W and Y, and S. pneumoniae vaccine, or must be vaccinated or willingness to start vaccination series at least 14 days prior to Day 1 14. In the opinion of the investigator, the subject is expected to comply adequately with all required study procedures and restrictions for 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Known congenital deficiency of C1s, C1r, C1q, C2, C4. Known variants in complement factor H, complement factor I, C3, and complement factor B or genomic rearrangements in the complement factor-H-related proteins are not exclusionary. 2. Receiving hemodialysis or peritoneal dialysis or anticipated to receive dialysis during the duration of this study. 3. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation during the study. 4. History of transfusion with blood or blood products, or plasmapheresis or plasma exchange, within 30 days prior to screening. 5. 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. 6. History of malignancy within 5 years prior to the screening visit, with the 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. 7. Any clinical or pathological evidence of monoclonal gammopathy of unclear or renal significance, lupus or other systemic autoimmune disease, or other conditions (eg, infection-associated disease or associated with another systemic disease, anti-phospholipid antibody syndrome with significant clinical disease, immune complex glomerulonephritis, immunoglobulin A [IgA] vasculitis with nephritis [Henoch-Schönlein purpura] or morphologic features of secondary membranous nephropathy). Presence of C3 or C5 nephritic factors (eg, autoantibodies directed at C3 or C5 convertase), in the absence of known infection or other systemic disease, are not exclusionary for this study. 8. Treatment with azathioprine, canakinumab, cyclophosphamide, cyclosporine, eculizumab, everolimus, hydroxychloroquine, infliximab, sirolimus, ravulizumab, systemic corticosteroids, tacrolimus, or any other systemic immunosuppressive or immunomodulatory therapies within 90 days OR within 180 days for anti-CD20 antibody therapies (eg, rituximab) prior to the screening visit. a. For subjects with C3G only, ongoing treatment with a stable dosing regimen of mycophenolate mofetil/mycophenolate sodium for at least 6 months prior to Day 1 Visit is allowed. 9. Treatment with renin inhibitors (eg, aliskiren) or sodium-glucose-cotransporter 2 (SGLT2) inhibitor within 60 days prior to Day 1. 10. 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. 11. Any of the following at screening: Hb 1.5 × ULN; serum albumin 1.4. a. Subjects with Grade 1 elevated bilirubin due to Gilbert’s syndrome are allowed to enroll 12. Any laboratory parameter at screening that is clinically significant and would represent a safety concern. 13. Clinically significant abnormal electrocardiogram (ECG) prior to dosing at the Day 1 Visit, including a QT interval corrected (QTcF) > 450 msec in males and QTcF > 470 msec in females, or ventri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the therapeutic potential of BCX9930 as assessed by proteinuria measures;Secondary Objective: To evaluate the safety and tolerability of BCX9930 To evaluate the therapeutic potential of BCX9930 as assessed by other measures of clinical benefit To evaluate effects of BCX9930 on light microscopic, immunofluorescence, and ultrastructural morphologic findings To characterize the effects of BCX9930 on blood and urine biomarkers of complement activation and consumption To evaluate the correlation of BCX9930-associated changes in blood and urine biomarkers of complement activation and consumption with changes in proteinuria;Primary end point(s): Change in 24-hour urinary protein excretion normalized to urine creatinine as measured by percentage change in uPCR from baseline;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Number and proportion of subjects with a uPCR response defined as: - Partial remission, = 50% reduction from baseline - Complete remission, = 500 mg/g - Normalization, = 200 mg/g • Change from baseline in 24-hour urinary protein excretion as measured by percentage change in urinary protein from baseline • Change from baseline in estimated glomerular filtration rate (eGFR) • Change from baseline in serum albumin • Number and proportion of subjects with the following parameters: - Protein = 3.5 g in a 24-hour urine collection - Serum albumin = 2.5 g/dL • Number and proportion of subjects with a morphologic response in each of the following categories assessed using a 0-4 scale: - Decreased endocapillary hypercellularity, mesangial hypercellularity, active crescents (if present) - Decreased acute tubular injury, interstitial inflammation, interstitial edema - Reduction in C3 and/or C4d glomerular staining - Reduction in the extent of deposits, clearing of deposits, or no additional active deposits as assessed by electron microscopy (EM) - No progression of chronic changes (ie, global, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis) • Change from baseline in constitutive blood levels of complement biomarkers, including but not limited to C3, Factor Bb, and soluble C5b-9 (sC5b-9) • Change from baseline in single void urine levels of complement biomarkers, including but not limited to Ba, C3a, and sC5b-9 normalized to urine creatinine • Change from baseline in complement biomarker measurements of ex vivo stimulation assays • Number and proportion of subjects with a treatment-emergent adverse event (TEAE) • Number and proportion of subjects who discontinue due to a TEAE • Number and proportion of subjects who experience a treatment-emergent serious adverse event (TESAE) • Number and proportion of subjects who experience a Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 TEAE • Number and proportion of subje | — |
Countries
France, Germany, Hungary, Italy, Spain, United Kingdom
Contacts
Public ContactProject Management
AMS Advanced Medical Services
Outcome results
None listed