Evaluating oral BCX9930 in renal diseases
- Conditions
- MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorderscomplement 3 glomerulopathyimmunoglobulin A nephropathyprimary membranous nephropathyMedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 10038359 - Renal and urinary disordersMedDRA version: 20.0Level: PTClassification code 10077827Term: C3 glomerulopathySystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2020-005855-19-HU
- Lead Sponsor
- BioCryst Pharmaceuticals Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 42
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 with evidence of disease
activity as, 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
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(including budesonide), tacrolimus, or any other systemic immunosuppressive or immunomodulatory therapies (eg. complement inhibitors)within 90 days OR mycophenolate mofetil/mycophenolate soldium treatment within 60 days for anti-CD20 antibody therapies (eg, rituximab) within 180 days, 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) inhibitors 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 < 8.5 g/dL; WBC < 2.5 × 109/L; ANC < 1.0 × 109/L; platelet count < 90 × 109/L; ALT, AST, ALP or total bilirubin > 1.5 × ULN; serum albumin < 1.5 g/dL; or international normalized ratio (INR) > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the therapeutic potential of BCX9930 as assessed by proteinuria measures;Secondary Objective: To evaluate the safety and tolerability of BCX9930<br>To evaluate the therapeutic potential of BCX9930 as assessed by other measures of clinical benefit <br>To evaluate effects on kidney biopsy morphologic findings <br>To characterize the effects of BCX9930 on blood and urine biomarkers of complement activation and consumption<br>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 52
- Secondary Outcome Measures
Name Time Method