Evaluating oral BCX9930 in renal diseases

Phase 1

Conditions: complement 3 glomerulopathyimmunoglobulin A nephropathyprimary membranous nephropathy
MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorders
MedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 10038359 - Renal and urinary disorders
MedDRA version: 20.0Level: PTClassification code 10077827Term: C3 glomerulopathySystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2020-005855-19-IT

Lead Sponsor: BIOCRYST PHARMACEUTICALS INC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2

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 >= 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

1.Known congenital deficiency of C1s, C1r, C1q, C2, C4.
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. Presence of C3 or C5 nephritic factors, 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 < 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 the Day 1 Visit, including a QT interval corrected (QTcF) > 450 msec in males and QTcF > 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.
14.Current use of a prohibited concomitant medication within 7 days prior to Day 1
15.Active serious bacterial, viral, or fungal infection or any other serious infection within 14 days of screening
16.Positive serology for HIV, or active infection with HBV or HCV
17.Positive drugs of abuse screen during screening
18.Pregnant, planning to become pregnant, or breastfeeding.
19.Known hypersensitivity to BCX9930 or any of i

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 of BCX9930 on light microscopic, immunofluorescence, and ultrastructural 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 24

Secondary Outcome Measures

Name	Time	Method

Related Trials